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[Objectives] This study investigated neuronal sources of slow cortical potentials (SCPs) evoked during vagus nerve stimulation (VNS) in patients with epilepsy who underwent routine electroencephalography (EEG) after implantation of the device. [Materials and Methods] We analyzed routine clinical EEG from 24 patients. There were 5 to 26 trains of VNS during EEG. To extract SCPs from the EEG, a high-frequency filter of 0.2 Hz was applied. These EEG epochs were averaged and used for source analyses. The averaged waveforms for each patient and their grand average were subjected to multidipole analysis. Patients with at least 50% seizure frequency reduction were considered responders. Findings from EEG analysis dipole were compared with VNS responses. [Results] VNS-induced focal SCPs whose dipoles were estimated to be located in several cortical areas including the medial prefrontal cortex, postcentral gyrus, and insula, with a significantly higher frequency in patients with a good VNS response than in those with a poor response. [Conclusions] This study suggested that some VNS-induced SCPs originating from the so-called vagus afferent network are related to the suppression of epileptic seizures.

Neuro-feedback (NFB) training by the self-regulation of slow potentials (SPs)0.5 Hz recorded from the vertex scalp has been applied for seizure suppression in patients with epilepsy. However, SP is highly susceptible to artifact contamination, such as the galvanic skin response (GSR). This study aimed to evaluate the correlation between SPs recorded from the scalp and intracranial electroencephalography (EEG) by event-related coherence analysis.The scalp and subdural SPs were simultaneously recorded during NFB training by the DC-EEG machine while undergoing invasive recordings before epilepsy surgery in 10 patients with refractory partial epilepsy. The SPs at the vertex electrode were used as a reference for coherence analysis.The coherence of SPs negatively correlated with the distance between the subdural and scalp electrodes. A significant negative correlation was noted between the linear subdural-scalp electrode distance and the coherence value (r = - 0.916, p 0.001).Scalp-recorded SPs from the vertex area primarily reflect the cortical activity of high lateral convexity.Our results strongly suggest that SPs in NFB recorded from the vertex scalp electrode is derived from the cortices of high lateral convexity but not from the artifacts, such as GSR.

OBJECTIVE To determine the characteristics of olfactory dysfunction in patients with temporal lobe epilepsy (TLE). METHODS Odor identification was assessed using the odor stick identification test for Japanese (OSIT-J, full score 12 points) in 65 patients with TLE and in 74 controls. RESULTS The mean OSIT-J score was significantly lower in patients with TLE (mean ± SD = 8.1 ± 2.8; median = 9) than in the control subjects (mean ± SD = 10.6 ± 1.1; median = 11) (P

We investigated whether vagus nerve stimulation (VNS) induces a positive shift of slow cortical potentials (SCPs) in patients with50% seizure reduction (responders) but not in non-responders.We analyzed routine clinical electroencephalograms (EEGs) from 24 patients who were undergoing seizure treatment by VNS. The patients were divided into 2 groups by hardware time constant (TC) of EEG: the TC 10-s group (10 patients) and TC 2-s group (14 patients). We compared SCPs at 5 electrodes (Cz and adjacent ones) between the 2 states of VNS: during stimulation and between stimulations. Seizure reduction was independently judged. Correlation between SCP (positivity or not) and seizure reduction (50% or not) was estimated.In the TC 10-s group, the correlation between SCP and seizure reduction was significant (p0.05) (i.e., both good results in 4 and both negative results in 5). In TC 2-s group, the correlation between SCP and seizure reduction was not significant (p=0.209).A positive shift of SCP recorded by using a TC of 10s could be a surrogate marker for VNS response.SCP could be a biomarker of good responders to VNS.

Objective The symptoms with optic ataxia suggest that simple and visually guided hand movements are controlled by 2 different neural substrates. To assess the differential frequency-coded posterior parietal cortex (PPC) role in planning visuo-motor goal-directed tasks, we studied the action specificity of event-related desynchronization (ERD) in this area. Methods We investigated cortical activity by electroencephalography, while 16 healthy subjects performed self-paced reaching or wrist extension (control) movements. Time–frequency representations were calculated for each movement during the preparatory period. Results ERD dynamics in upper alpha-band indicated that preparing a goal-directed action activates contralateral PPC to the moving hand around 1.2 s before starting the movement, while this activation is later (around 0.7 s) in preparing a not-goal-directed action. The posterior dominant rhythm had peak frequency of lower alpha-band at bilateral parietal. Conclusions Posterior parietal cortex encodes goal-directed movement preparation through upper alpha-band activity, whereas general attention is processed via lower alpha-band oscillations. Significance Preparing to reach an object engages posterior parietal cortex earlier than a not-goal directed movement.

Objective The pathophysiological mechanisms of partial reading epilepsy are still unclear. We delineated the spatial–temporal characteristics of reading-induced epileptic spikes and hemodynamic activation in a patient with partial reading epilepsy. Methods Magnetoencephalography (MEG) was recorded during silent letter-by-letter reading, and the source of reading-induced spikes was estimated using equivalent current dipole (ECD) analysis. Diffusion tractography was employed to determine if the white matter pathway connected spike initiation and termination sites. Functional magnetic resonance imaging (fMRI) was employed to determine the spatial pattern of hemodynamic activation elicited by reading. Results In 91 spike events, ECDs were clustered in the left posterior basal temporal area (pBTA) during Katakana reading. In 8 of these 91 events, when the patient continued to read >30 min, another ECD cluster appeared in the left ventral precentral gyrus/frontal operculum with a time-difference of ∼24 ms. Probabilistic diffusion tractography revealed that the long segment of the arcuate fasciculus connected these two regions. fMRI conjunction analysis indicated that both Katakana and Kanji reading activated the left pBTA, but Katakana activated the left lateral frontal areas more extensively than Kanji. Conclusions Prolonged reading of Katakana induced hyper-activation of the cortical network involved in normal language function, concurrently serving as the seizure onset and symptomatogenic zones. Significance Reflex epilepsy is believed to result from intrinsic hyper-excitability in the cortical regions recruited during behavioral states that trigger seizures. Our case shows that reading epilepsy can arise from a hyperexcitable network of cortical regions. Physiological activation of this network can have cumulative effects, resulting in greater reciprocal network propagation and electroclinical seizures. These effects, in turn, may give insights into the brain networks recruited by reading.

Objective Decreased early Bereitschaftspotential (BP) is one of the electrophysiological characteristics in patients with Parkinson's disease (PD). We examined whether PD patients could increase BP amplitude by means of neuro-feedback (NFB) training for their slow cortical potentials (SCPs). Methods We worked with 10 PD patients and 11 age-matched controls. BP was measured for self-paced button pressing by their right thumb. The subjects were instructed to make the introspective efforts to produce negative SCPs (negativation). The one-day session consisted of three trials, that is, the first BP, NFB training and the second BP, and each patient performed this routine for 2–4days. Amplitudes of the first and second BPs were compared between the two groups that were divided depending on NFB performance. Results Good NFB performance had the tendency of larger early BP in the second BP recording than in the first one, whereas in the poor NFB performance the early BP was smaller in the second BP recording than in the first one in both patient and normal groups ( p Conclusions Good NFB performance of negativation could increase excitatory field potentials of pyramidal cells for the generation of early BP. Significance Voluntary regulation of SCPs could enhance BP in PD patients and in aged controls.

Objective To investigate the brain networks involved in epileptogenesis/encephalopathy associated with hypothalamic hamartoma (HH) by EEG with functional MRI (EEG-fMRI), and evaluate its efficacy in locating the HH interface in comparison with subtraction ictal SPECT coregistered to MRI (SISCOM). Methods Eight HH patients underwent EEG-fMRI. All had gelastic seizures (GS) and 7 developed other seizure types. Using a general linear model, spike-related activation/deactivation was analyzed individually by applying a hemodynamic response function before, at, and after spike onset (time-shift model=−8–+4s). Group analysis was also performed. The sensitivity of EEG-fMRI in identifying the HH interface was compared with SISCOM in HH patients having unilateral hypothalamic attachment. Results EEG-fMRI revealed activation and/or deactivation in subcortical structures and neocortices in all patients. 6/8 patients showed activation in or around the hypothalamus with the HH interface with time-shift model before spike onset. Group analysis showed common activation in the ipsilateral hypothalamus, brainstem tegmentum, and contralateral cerebellum. Deactivation occurred in the default mode network (DMN) and bilateral hippocampi. Among 5 patients with unilateral hypothalamic attachment, activation in or around the ipsilateral hypothalamus was seen in 3 using EEG-fMRI, whereas hyperperfusion was seen in 1 by SISCOM. Significance Group analysis of this preliminary study may suggest that the commonly activated subcortical network is related to generation of GS and that frequent spikes lead to deactivation of the DMN and hippocampi, and eventually to a form of epileptic encephalopathy. Inter-individual variance in neocortex activation explains various seizure types among patients. EEG-fMRI enhances sensitivity in detecting the HH interface compared with SISCOM.

Parieto‐frontal network is essential for sensorimotor integration in various complex behaviors, and its disruption is associated with pathophysiology of apraxia and visuo‐spatial disorders. Despite advances in knowledge regarding specialized cortical areas for various sensorimotor transformations, little is known about the underlying cortico‐cortical connectivity in humans. We investigated inter‐areal connections of the lateral parieto‐frontal network in vivo by means of cortico‐cortical evoked potentials (CCEPs). Six patients with epilepsy and one with brain tumor were studied. With the use of subdural electrodes implanted for presurgical evaluation, network configuration was investigated by tracking the connections from the parietal stimulus site to the frontal site where the maximum CCEP was recorded. It was characterized by (i) a near‐to‐near and distant‐to‐distant, mirror symmetric configuration across the central sulcus, (ii) preserved dorso‐ventral organization (the inferior parietal lobule to the ventral premotor area and the superior parietal lobule to the dorsal premotor area), and (iii) projections to more than one frontal cortical sites in 56% of explored connections. These findings were also confirmed by the standardized parieto‐frontal CCEP connectivity map constructed in reference to the Jülich cytoarchitectonic atlas in the MNI standard space. The present CCEP study provided an anatomical blueprint underlying the lateral parieto‐frontal network and demonstrated a connectivity pattern similar to non‐human primates in the newly developed inferior parietal lobule in humans. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.

Introduction A cortical region showing an event-related desynchronization (ERD) in the electroencephalographic (EEG) alpha power indicates that it is activated in preparation for voluntary movements. The aim of this study is to search for visual and spatial condition that degree and distribution of alpha band ERD by loading greater spatial attention with movement. Methods We measured movement-related ERD of scalp EEG over central to occipital areas. Just like Libet’s Clock paradigm, subjects were seated in front of a computer screen that displayed a clock rotating at 3 s per cycle. They were instructed to register in mind the onset time of the self-paced movement. After the movement, they reported the position of the clock when the movement took place. [Measurement 1] Two types of movement tasks were executed while the clock rotating direction is clockwise. In reaching trials, subjects reached the center of the screen with their right hand. In control trials, subjects performed a simple right wrist extension on the chair armrest. [Measurement 2] A wrist extension movement with right and left hand was performed in each of two kinds of rotating directions (clockwise and counterclockwise) of clock. Data analysis: We analyzed the effect of clock position, clock rotating direction, electrode position, side of hand, and type of movement to the EEG activity before the movement onset. The time-frequency representation of the EEG power was calculated using short-time Fourier transformation. Results [Measurement 1] In wrist extension, alpha band ERD was significantly greater in bilateral parieto-occipital area when clock position was in the left visual field (LVF) (while the clock is moving up) compared with the right visual field (RVF) (while the clock is moving down). Reaching trials showed the significant alpha band ERD in bilateral parieto-occipital area in both trials of LVF and RVF. [Measurement 2] There was a significant interaction between clock rotating direction and clock position that showed alpha band ERD in bilateral parieto-occipital area when the clock is moving up was significantly greater than that when the clock is moving down. This modulation is in common for the both left hand right hand movement. The common finding in measurement 1 and 2 is that alpha band ERD in the posterior area was greater in ipsilateral hemisphere to attended visual hemi-field compared with contralateral hemisphere. Conclusion We showed that alpha band power at motor preparation stage was significantly altered in posterior cortex by applying an appropriate spatial load in peripheral visual field without changing the movement itself.

Focal seizures arising from the temporal lobe (TL seizures) resemble those from supplementary motor area (SMA) with resepct to ictal dystonic and/or tonic posturing. The aim of this study is to clarify the symptomatic difference and then underlying mechanism between TL- and SMA seizures by careful observation of ictal posturing. Among patients with partial epilepsy who performed long-term video-EEG monitoring from 1992 to 2014, we employed 13 patients with TL seizures showing discrete dystonic posture and 12 patients with SMA seizures showing clear abnormal tonic posture. We reviewed the posturing and the movement direction of the shoulder, elbow and wrist joints of both seizures. As the results, shoulder adduction was observed significantly more in TL seizures than SMA seizures ( p p

Objective Unilateral asterixis has been reported in patients with thalamic lesion. This study aims at elucidating the pathophysiology of the thalamic asterixis. Methods Two cases with unilateral asterixis caused by an infarction in the lateral thalamus were studied by analysing the asterixis-related cortical activities, transcranial magnetic stimulation (TMS) for motor cortex excitability and probabilistic diffusion tractography for the thalamo-cortical connectivity. Results Averaging of electroencephalogram (EEG) time-locked to the asterixis revealed rhythmic oscillations of a beta band at the central area contralateral to the affected hand. TMS revealed a decrease in the motor evoked potential (MEP) amplitude and a prolongation of the silent period (SP). The anatomical mapping of connections between the thalamus and cortical areas using a diffusion-weighted image (DWI) showed that the lateral thalamus involved by the infarction was connected to the premotor cortex, the primary motor cortex (M1) and the primary somatosensory cortex (S1) of the corresponding hemisphere. Conclusions The thalamic asterixis is mediated by the sensorimotor cortex, which is subjected to excessive inhibition as a result of the thalamic lesion involving the ventral lateral nucleus. Significance This is the first demonstration of participation of the sensorimotor cortex in the generation of asterixis due to the lateral thalamic lesion.

Objective To clarify the clinical features and mechanism of the transience of myoclonus in patients with a transient myoclonic state with asterixis (TMA). Methods We investigated the clinical and eletrophysiological profiles of 6 patients with TMA (age: 84±3 years). During an asymptomatic period, somatosensory evoked potentials (SEPs) were recorded in all 6 patients and motor evoked potentials (MEPs) were examined in 1 patient. SEPs were recorded and jerk-locked back averaging (JLA) was performed in 2 patients while symptomatic. SEPs were also recorded from 8 aged control subjects (age: 68±5 years). Results All TMA patients had mild chronic systemic diseases. During an asymptomatic period, SEP amplitudes were not significantly enlarged in comparison with control subjects, and MEPs were normal. Examination of 2 patients during symptomatic period indicated no enlargement of SEP amplitudes and JLA disclosed a positive spike preceding myoclonic jerks. In one of these patients, the amplitude of the positive spike decreased once myoclonus improved. Conclusion TMA occurred in aged patients with mild chronic systemic diseases. JLA findings and the absence of giant SEPs further support that TMA is a cortical non-reflex myoclonus. In addition, transient hyperexcitability at the primary motor cortex disclosed by JLA correlated well with its transient symptoms.

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.

Recently, neuro-feedback (NFB) training by self-regulation of slow cortical potentials (SCPs) recorded at scalp vertex has been applied for seizure suppression in patients with refractory epilepsy. However, it is not clear whether the whole cortices or parts of the cortices contribute to the scalp-recorded SCPs. It is also uncertain whether scalp-recorded SCPs may contain slow component of galvanic-skin response. To clarify the two questions, we evaluated the correlation of SCPs between scalp and subdural recording by means of the coherence analysis. In 5 patients with refractory partial epilepsy while invasive recording was done before epilepsy surgery, scalp and subdural SCPs were recorded simultaneously during NFB training by means of DC-EEG machine (IRB#C533). SCPs in C1 or C2 (contralateral to the subdural electrodes) was employed as a reference to the coherence analysis. As a result, for scalp-recorded SCPs, SCPs on the primary sensorimotor cortices had the highest correlation, than those of lateral ( P = 0.02) and basal temporal ( P = 0.01) cortices. It is most likely that scalp-recorded SCPs from the scalp vertex area exclusively could reflect SCPs of the cortices of the lateral convexity close to the vertex, and thus that scalp-recorded SCPs do not contain the galvanic skin response.