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Noninvasive brain imaging studies have shown that higher visual processing of objects occurs in neural populations that are separable along broad semantic categories, particularly living versus nonliving objects. However, because of their limited temporal resolution, these studies have not been able to determine whether broad semantic categories are also reflected in the dynamics of neural interactions within cortical networks. We investigated the time course of neural propagation among cortical areas activated during object naming in 12 patients implanted with subdural electrode grids prior to epilepsy surgery, with a special focus on the visual recognition phase of the task. Analysis of event-related causality revealed significantly stronger neural propagation among sites within ventral temporal lobe (VTL) at early latencies, around 250 ms, for living objects compared to nonliving objects. Differences in other features, including familiarity, visual complexity, and age of acquisition, did not significantly change the patterns of neural propagation. Our findings suggest that the visual processing of living objects relies on stronger causal interactions among sites within VTL, perhaps reflecting greater integration of visual feature processing. In turn, this may help explain the fragility of naming living objects in neurological diseases affecting VTL.

Objective Cortico-cortical evoked potential (CCEP) by single-pulse electrical stimulation (SPES) is useful to investigate effective connectivity and cortical excitability. We aimed to clarify the safety of CCEPs. Methods We retrospectively analyzed 29 consecutive patients with intractable partial epilepsy undergoing chronic subdural grid implantation and CCEP recording. Repetitive SPES (1 Hz) was systematically applied to a pair of adjacent electrodes over almost all electrodes. We evaluated the incidences of afterdischarges (ADs) and clinical seizures. Results Out of 1283 electrode pairs, ADs and clinical seizures were observed in 12 and 5 pairs (0.94% and 0.39%, per electrode pair) in 7 and 3 patients (23.3% and 10.0%, per patient), respectively. Of the 18–82 pairs per patient, ADs and clinical seizures were induced in 0–4 and 0–3 pairs, respectively. Stimulating 4 SOZ (seizure onset zone) (2.5%) and 8 non-SOZ pairs (0.75%) resulted in ADs. We observed clinical seizures in stimulating 4 SOZ (2.5%) and 1 non-SOZ pair (0.09%). The incidence of clinical seizures varied significantly between SOZ and non-SOZ stimulations (p = 0.001), while the difference in AD incidence tended towards significance (p = 0.058). Conclusion Although caution should be taken in stimulating SOZ, CCEP is a safe procedure for presurgical evaluation. Significance CCEP is safe under the established protocol.

Objectives: The association between neurocognitive decline and changing functional connectivity in glioma patients remains unclear. This study aimed to investigate the correlation between brain oscillatory activity or functional connectivity and neurocognitive function in patients with left frontal glioma using resting-state electroencephalography (EEG).Methods: This was an observational study and conforms to all the STROBE guidelines. Participants comprised 18 consecutive patients diagnosed with newly left frontal glioma between April 2010 and March 2021 who underwent neuropsychological examination and electroencephalography. Forty seconds of artifact-free electroencephalographic data were selected, and current source density (CSD) or lagged phase synchronization (LPS) were analyzed using exact low-resolution electromagnetic tomography (eLORETA). We investigated associations of CSD and LPS with the Wechsler adult intelligence scale (WAIS), the Wechsler memory scale-revised (WMS-R), and the western aphasia battery aphasia quotient (WAB AQ) scores. Results: Among the 18 consecutive patients (mean age, 43 ± 13.15 years), the mean WAIS full-scale intelligence quotient (FSIQ), WMS-R general memory (GM), and WAB AQ scores were within standard value ranges, and none had aphasia. The correlation analysis showed lower GM score was associated with higher LPS value between the right anterior prefrontal cortex and the left superior parietal lobule in the beta1 band (13–20 Hz, R = -0.802, P = 0.012)Conclusion: Increases in functional connectivity between certain brain regions may potentially represent more common and early network changes in the brain that are associated with cognitive declines in patients with left frontal glioma.

The areas that directly inhibit motor responses in the human brain remain not fully clarified, although the pre-supplementary motor area and lateral premotor areas have been implicated. The objective of the present study was to delineate the critical areas for response inhibition and the associated functional organization of the executive action control system in the frontal lobe. The subjects were eight intractable focal epilepsy patients with chronic subdural or depth electrode implantation for presurgical evaluation covering the frontal lobe (five for left hemisphere, three for right). We recorded event-related potentials to a Go/No-Go task. We then applied a brief 50 Hz electrical stimulation to investigate the effect of the intervention on the task. Brief stimulation was given to the cortical areas generating discrete event-related potentials specific for the No-Go trials (1–3 stimulation sites/patient, a total of 12 stimulation sites). We compared the locations of event-related potentials with the results of electrical cortical stimulation for clinical mapping. We also compared the behavioural changes induced by another brief stimulation with electrical cortical stimulation mapping. As the results, anatomically, No-Go-specific event-related potentials with relatively high amplitude, named ‘large No-Go event-related potentials’, were observed predominantly in the secondary motor areas, made up of the supplementary motor area proper, the pre-supplementary motor area, and the lateral premotor areas. Functionally, large No-Go event-related potentials in the frontal lobe were located at or around the negative motor areas or language-related areas. Brief stimulation prolonged Go reaction time at most stimulation sites (66.7%) [P

The spatiotemporal dynamics of interaction between slow (delta or infraslow) waves and fast (gamma) activities during wakefulness and sleep are yet to be elucidated in human electrocorticography (ECoG). We evaluated phase-amplitude coupling (PAC), which reflects neuronal coding in information processing, using ECoG in 11 patients with intractable focal epilepsy. PAC was observed between slow waves of 0.5–0.6 Hz and gamma activities, not only during light sleep and slow-wave sleep (SWS) but even during wakefulness and rapid eye movement (REM) sleep. While PAC was high over a large region during SWS, it was stronger in the posterior cortical region around the temporoparietal junction than in the frontal cortical region during REM sleep. PAC tended to be higher in the posterior cortical region than in the frontal cortical region even during wakefulness. Our findings suggest that the posterior cortical region has a functional role in REM sleep and may contribute to the maintenance of the dreaming experience.

BACKGROUND Benign adult familial myoclonus epilepsy (BAFME) is one of the diseases that cause cortical myoclonus (CM) with giant somatosensory evoked potentials (SEPs). There are no useful diagnostic biomarkers differentiating BAFME from other CM diseases. OBJECTIVE To establish reliable biomarkers including high-frequency oscillations (HFOs) with giant SEPs for the diagnosis of BAFME. METHODS This retrospective case study included 49 consecutive CM patients (16 BAFME and 33 other CM patients) who exhibited giant P25 or N35 SEPs. SEPs were processed by a band-pass filter of 400-1000 Hz to analyze HFOs. Clinical and SEP findings were compared between (1) BAFME and other CM groups and (2) patients with presence and absence of P25-HFOs (HFOs superimposed on giant P25). The diagnostic power of each factor for BAFME was calculated. RESULTS All 16 BAFME patients showed SEP P25-HFOs with significantly higher occurrence (P

We experienced 3 adult patients with intractable focal epilepsy treated by levetiracetam (LEV) as polytherapy, who showed paradoxical effect (PE). Starting dose of LEV was small (62.5, 250 mg/day) and we gradually increased by less than 250 mg/day, every more than 2 weeks. Within 6 months after LEV was added, LEV of 750 to 1,000 mg/day brought reduction of seizure frequency. Serum concentration of LEV was 13.3 and 14.0 μg/ml. In order to obtain better seizure control, LEV was increased up to 1,000-2,500 mg/day (19.3-35.0 μg/ml) within one year, and they developed PE. They all showed increased habitual seizures, occurring in cluster. Once dose of LEV deceased down to what produced the maximum seizure suppression, all of the patients regained the better seizure control. It is most likely that at least in some patients like present 3 cases, PE of LEV may express U curve association between dose and effect and that it was only delineated by slow titration.

Enzyme-inducing anti-seizure medications (EIASMs) may contribute to the development of complications such as fracture and cardiovascular disease. The objective of the study was to determine whether the use of EIASMs is associated with a higher risk of fracture and cardiovascular outcome in young Japanese patients with epilepsy.Adult patients diagnosed with epilepsy and initiated a monotherapy with an anti-seizure medication (ASM) between 2008 and 2018 were included in the study. The primary outcomes were the occurrence of acute myocardial infarction (AMI) or stroke. The secondary outcome was fracture. We performed a propensity score-matched analysis (1:1) to control for imbalances in patient characteristics, and the matched hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models.Of the 7115 eligible patients, 626 (8.79%) initiated treatment with EIASMs. The median age of the patients was 44 years (interquartile range: 31-54 years), and 56.2% were male. Propensity score matching generated 626 matched pairs of patients treated with EIASMs and non-EIASMs. There were no significant differences in the risk of stroke (EIASM group: n = 28[4.47%], non-EIASM group: n = 22[3.51%], HR: 1.47, 95% CI: 0.79-2.72, p = 0.22) or fracture (EIASM group: n = 7[1.12%], non-EIASM group: n = 5[0.80%], HR: 1.00, 95% CI: 0.29-3.45, p = 1.00) between the two groups. The hazard ratio for the occurrence of AMI could not be calculated due to the small number of events (EIASM group: n = 0[0.00], non-EIASM group: n = 2[0.32]).Our cohort study did not find increased risk of the occurrence of stroke, AMI, or fracture hospitalization with the use of enzyme-inducing ASMs. Although the findings suggested that exposure to EIASMs does not appear to increase the risk of complications in young patients, caution should be taken as patients with epilepsy tend to take medication in the long run.

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.

Any given area in human cortex may receive input from multiple, functionally heterogeneous areas, potentially representing different processing threads. Alpha (8–13 Hz) and beta oscillations (13–20 Hz) have been hypothesized by other investigators to gate local cortical processing, but their influence on cortical responses to input from other cortical areas is unknown. To study this, we measured the effect of local oscillatory power and phase on cortical responses elicited by single-pulse electrical stimulation (SPES) at distant cortical sites, in awake human subjects implanted with intracranial electrodes for epilepsy surgery. In 4 out of 5 subjects, the amplitudes of corticocortical evoked potentials (CCEPs) elicited by distant SPES were reproducibly modulated by the power, but not the phase, of local oscillations in alpha and beta frequencies. Specifically, CCEP amplitudes were higher when average oscillatory power just before distant SPES (−110 to −10 ms) was high. This effect was observed in only a subset (0–33%) of sites with CCEPs and, like the CCEPs themselves, varied with stimulation at different distant sites. Our results suggest that although alpha and beta oscillations may gate local processing, they may also enhance the responsiveness of cortex to input from distant cortical sites.

The cortical motor areas are activated not only during contralateral limb movements but also during ipsilateral limb movements. Although these ipsilateral activities have been observed in several brain imaging studies, their functional role is poorly understood. Due to its high temporal resolution and low susceptibility to artifacts from body movements, the electrocorticogram (ECoG) is an advantageous measurement method for assessing the human brain function of motor behaviors. Here, we demonstrate that contra- and ipsilateral movements share a similarity in the high-frequency band of human ECoG signals. The ECoG signals were measured from the unilateral sensorimotor cortex while patients conducted self-paced movements of different body parts, contra- or ipsilateral to the measurement side. The movement categories (wrist, shoulder, or ankle) of ipsilateral movements were decoded as accurately as those of contralateral movements from spatial patterns of the high-frequency band of the precentral motor area (the primary motor and premotor areas). The decoder, trained in the high-frequency band of ipsilateral movements generalized to contralateral movements, and vice versa, confirmed that the activity patterns related to ipsilateral limb movements were similar to contralateral ones in the precentral motor area. Our results suggest that the high-frequency band activity patterns of ipsilateral and contralateral movements might be functionally coupled to control limbs, even during unilateral movements.

Speaking in sentences requires selection from contextually determined lexical representations. Although posterior temporal cortex (PTC) and Broca’s areas play important roles in storage and selection, respectively, of lexical representations, there has been no direct evidence for physiological interactions between these areas on time scales typical of lexical selection. Using intracranial recordings of cortical population activity indexed by high-gamma power (70–150 Hz) modulations, we studied the causal dynamics of cortical language networks while epilepsy surgery patients performed a sentence completion task in which the number of potential lexical responses was systematically varied. Prior to completion of sentences with more response possibilities, Broca’s area was not only more active, but also exhibited more local network interactions with and greater top-down influences on PTC, consistent with activation of, and competition between, more lexical representations. These findings provide the most direct experimental support yet for network dynamics playing a role in lexical selection among competing alternatives during speech production.

Objective We aimed at clarifying the clinical significance of the responses evoked by human entorhinal cortex (EC) electrical stimulation by means of cortico‐cortical evoked potentials (CCEPs). Methods We enrolled nine patients with medically intractable medial temporal lobe epilepsy who underwent invasive presurgical evaluations with subdural or depth electrodes. Single‐pulse electrical stimulation was delivered to the EC and fusiform gyrus (FG), and their evoked potentials were compared. The correlation between the evoked potentials and Wechsler Memory Scale‐Revised (WMS‐R) score was analyzed to investigate whether memory circuit was involved in the generation of the evoked potentials. Results In most electrodes placed on the neocortex, EC stimulation induced unique evoked potentials with positive polarity, termed as “widespread P1” (P1w). Compared with FG stimulation, P1w induced by EC stimulation were distinguished by their high occurrence rate, short peak latency (mean: 20.1 ms), small peak amplitude, and waveform uniformity among different recording sites. A stimulation of more posterior parts of the EC induced P1w with shorter latency and larger amplitude. P1w peak amplitude had a positive correlation (r = .69) with the visual memory score of the WMS‐R. In one patient, with depth electrode implanted into the hippocampus, the giant evoked potentials were recorded in the electrodes of the anterior hippocampus and EC near the stimulus site. Conclusions The human EC electrical stimulation evoked the short‐latency potentials in the broad neocortical regions. The origin of P1w remains unclear, although the limited evidence suggests that P1w is the far‐field potential by the volume conduction of giant evoked potential from the EC itself and hippocampus. The significance of the present study is that those evoked potentials may be a potential biomarker of memory impairment in various neurological diseases, and we provided direct evidence for the functional subdivisions along the anterior–posterior axis in the human EC.

Wakefulness and sleep arise from global changes in brain physiology that may also govern the flow of neural activity between cortical regions responsible for perceptual processing versus planning and action. To test whether and how the sleep/wake cycle affects the overall propagation of neural activity in large-scale brain networks, we applied single-pulse electrical stimulation (SPES) in patients implanted with intracranial EEG electrodes for epilepsy surgery. SPES elicited cortico-cortical spectral responses at high-gamma frequencies (CCSR(HG), 80–150 Hz), which indexes changes in neuronal population firing rates. Using event-related causality (ERC) analysis, we found that the overall patterns of neural propagation among sites with CCSR(HG) were different during wakefulness and different sleep stages. For example, stimulation of frontal lobe elicited greater propagation toward parietal lobe during slow-wave sleep than during wakefulness. During REM sleep, we observed a decrease in propagation within frontal lobe, and an increase in propagation within parietal lobe, elicited by frontal and parietal stimulation, respectively. These biases in the directionality of large-scale cortical network dynamics during REM sleep could potentially account for some of the unique experiential aspects of this sleep stage. Together these findings suggest that the regulation of conscious awareness and sleep is associated with differences in the balance of neural propagation across large-scale frontal-parietal networks.

Objective We aimed to delineate the engagement of cortico-cortical and cortico-subcortical networks in the generation of epileptic spasms (ES) using integrated neurophysiological techniques. Methods Seventeen-year-old male patient with intractable ES underwent chronic subdural electrode implantation for presurgical evaluation. Networks were evaluated in ictal periods using high-frequency oscillation (HFO) analysis and in interictal periods using magnetoencephalography (MEG) and simultaneous electroencephalography, and functional magnetic resonance imaging (EEG-fMRI). Cortico-cortical evoked potentials (CCEPs) were recorded to trace connections among the networks. Results Ictal HFO revealed a network comprising multilobar cortical regions (frontal, parietal, and temporal), but sparing the positive motor area. Interictally, MEG and EEG-fMRI revealed spike-and-wave-related activation in these cortical regions. Analysis of CCEPs provided evidence of connectivity within the cortico-cortical network. Additionally, EEG-fMRI results indicate the involvement of subcortical structures, such as bilateral thalamus (predominantly right) and midbrain. Conclusions In this case study, integrated neurophysiological techniques provided converging evidence for the involvement of a cortico-cortical network (sparing the positive motor area) and a cortico-subcortical network in the generation of ES in the patient. Significance Cortico-cortical and cortico-subcortical pathways, with the exception of the direct descending corticospinal pathway from the positive motor area, may play important roles in the generation of ES.

Promnesia is a feeling of familiarity and foreknowledge and is a manifestation of simple partial seizures (focal aware seizures). It is similar to deja vu and has been reported to be a rare symptom in patients with temporal lobe epilepsy. Here, we investigated the clinical characteristics in 4 patients with partial epilepsy presenting promnesia. Three out of 4 patients showed abnormal electroencephalography (EEG) and/or MRI findings in the temporal lobe. Furthermore, in 2 patients, promnesia was the only aura. It is important to actively obtain medical history of patients about promnesia because this is useful for identifying the epileptic focus. Further cases need to be analyzed to evaluate the sensitivity and specificity of promnesia for diagnosis and therapy of partial epilepsy.

Sleep-induced changes in human brain connectivity/excitability and their physiologic basis remain unclear, especially in the frontal lobe. We investigated sleep-induced connectivity and excitability changes in 11 patients who underwent chronic implantation of subdural electrodes for epilepsy surgery. Single-pulse electrical stimuli were directly injected to a part of the cortices, and cortico-cortical evoked potentials (CCEPs) and CCEP-related high-gamma activities (HGA: 100-200 Hz) were recorded from adjacent and remote cortices as proxies of effective connectivity and induced neuronal activity, respectively. HGA power during the initial CCEP component (N1) correlated with the N1 size itself across all states investigated. The degree of cortical connectivity and excitability changed during sleep depending on sleep stage, approximately showing dichotomy of awake vs. non-rapid eye movement (REM) [NREM] sleep. On the other hand, REM sleep partly had properties of both awake and NREM sleep, placing itself in the intermediate state between them. Compared with the awake state, single-pulse stimulation especially during NREM sleep induced increased connectivity (N1 size) and neuronal excitability (HGA increase at N1), which was immediately followed by intense inhibition (HGA decrease). The HGA decrease was temporally followed by the N2 peak (the second CCEP component), and then by HGA re-increase during sleep across all lobes. This HGA rebound or re-increase of neuronal synchrony was largest in the frontal lobe compared with the other lobes. These properties of sleep-induced changes of the cortex may be related to unconsciousness during sleep and frequent nocturnal seizures in frontal lobe epilepsy.

Study objectives To investigate the changes in cortical neural responses induced by external inputs during phasic rapid eye movement (p-REM) sleep. Methods Single-pulse electrical stimulation (SPES) was directly applied to the human cortex during REM sleep through subdural electrodes, in seven patients who underwent invasive presurgical evaluation for intractable partial epilepsy. SPES was applied to parts of the cortex through the subdural electrodes, and induced cortical responses were recorded from adjacent and remote cortical areas. Phase-locked corticocortical-evoked potentials (CCEPs) and nonphase-locked or induced CCEP-related high gamma activity (CCEP-HGA, 100-200 Hz), which are considered proxies for cortical connectivity and cortical excitability, respectively, were compared among wakefulness, p-REM (within ±2 seconds of significant bursts of REM), and tonic REM (t-REM) (periphasic REM) periods. Results During REM sleep, SPES elicited a transient increase in CCEP-HGA, followed by a subsequent decrease or suppression. The HGA suppression during both p-REM and t-REM was stronger than during wakefulness. However, its suppression during p-REM was weaker than during t-REM. On the other hand, the CCEP waveform did not show any significant difference between the two REM periods. Conclusions Cortical excitability to exogenous input was different between p-REM and t-REM. The change of the cortical excitability in p-REM was directed toward wakefulness, which may produce incomplete short bursts of consciousness, leading to dreams.

The preservation of language function during brain surgery still poses a challenge. No intraoperative methods have been established to monitor the language network reliably. We aimed to establish intraoperative language network monitoring by means of cortico-cortical evoked potentials (CCEPs). Subjects were six patients with tumors located close to the arcuate fasciculus (AF) in the language-dominant left hemisphere. Under general anesthesia, the anterior perisylvian language area (AL) was first defined by the CCEP connectivity patterns between the ventrolateral frontal and temporoparietal area, and also by presurgical neuroimaging findings. We then monitored the integrity of the language network by stimulating AL and by recording CCEPs from the posterior perisylvian language area (PL) consecutively during both general anesthesia and awake condition. High-frequency electrical stimulation (ES) performed during awake craniotomy confirmed language function at AL in all six patients. Despite an amplitude decline (≤32%) in two patients, CCEP monitoring successfully prevented persistent language impairment. After tumor removal, single-pulse ES was applied to the white matter tract beneath the floor of the removal cavity in five patients, in order to trace its connections into the language cortices. In three patients in whom high-frequency ES of the white matter produced naming impairment, this “eloquent” subcortical site directly connected AL and PL, judging from the latencies and distributions of cortico- and subcortico-cortical evoked potentials. In conclusion, this study provided the direct evidence that AL, PL, and AF constitute the dorsal language network. Intraoperative CCEP monitoring is clinically useful for evaluating the integrity of the language network. Hum Brain Mapp 35:4345–4361, 2014. © 2014 Wiley Periodicals, Inc.

We aimed to clarify that high frequency activity (HFA) of cortico-cortical evoked potentials (CCEPs), elicited by single pulse electrical stimulation (SPES), reflects cortical excitability.We recruited 16 patients with refractory partial epilepsy who had chronic subdural electrode implantation for presurgical evaluation. A repetitive SPES was given to (1) the seizure onset zone (SOZ) and (2) the control cortices (non-seizure onset zone: nSOZ). CCEPs were recorded from the neighboring cortices within SOZ and nSOZ. We applied short-time Fourier transform to obtain the induced responses for the timing of early (50ms after SPES) and late CCEP components and analyzed the logarithmic power change for ripple (200Hz) and fast ripple (200Hz) bands.Twenty-one clear CCEPs were recorded for both the SOZ and nSOZ. The HFA power of early CCEPs in SOZ significantly increased compared to that in nSOZ in both frequency bands, particularly in mesial temporal lobe epilepsy (MTLE).Similar to the features of spontaneous pathological HFOs, the power of stimulus-induced HFAs in SOZ were greater than that outside SOZ, particularly in MTLE.HFA overriding CCEPs can be a surrogate marker of cortical excitability in epileptic focus.

Previous non-invasive studies have proposed that the deeply seated region of the medial frontal cortex engages in conflict processing in humans, but its core region has remained to be elucidated. By means of direct cortical stimulation, which excels other techniques in temporal and spatial resolutions and in the capacity of producing transient, functional impairment even in the deeply located cortices, we attempted to obtain direct evidence that the pre-supplementary motor area (pre-SMA) actively engages in conflict processing. Subject was a patient with right frontal lobe epilepsy who underwent invasive presurgical evaluation with subdural electrodes placed on the medial and lateral frontal cortices. During a conflict task – modified Eriksen flanker task, direct cortical stimulation was delivered time-locked to the task at the inferior part of the medial superior frontal gyrus (inferior medial SFG), the superior part of the medial SFG, and the middle frontal gyrus. By adopting the session of sham stimulation that was employed as a within-block control, event-related potentials (ERPs) were recorded from the medial and lateral frontal cortices. The inferior medial SFG showed a significant ERP difference between trials with more and less conflict, while the other frontal cortices did not. Among the three stimulus sites, only stimulation of the inferior medial SFG significantly prolonged reaction time in trials with more conflict. Anatomically, the inferior medial SFG corresponded with the pre-SMA (Brodmann area 8). It was located 1–2 cm rostral to the vertical anterior commissure line where cortical stimulation elicited arrest of motion (the supplementary negative motor area). Functionally, this area corresponded to the dorso-rostral portion of the activation loci in previous neuroimaging studies focusing on conflict processing. By combining epicortical ERP recording and direct cortical stimulation in a human brain, this study, for the first time, presented one direct piece of evidence that the pre-SMA actively participates in conflict processing.

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.

We report a case of a 35-year-old man with histologically confirmed neurosarcoidosis who developed recurrent episodes of right-hemispheric dysfunction with diffuse cortical lesions of the right hemisphere on magnetic resonance imaging (MRI). A brain biopsy revealed granulomatous inflammatory cells in both the subarachnoid space and Virchow-Robin space, which might relate to the recurrent neurological dysfunction and MRI findings.

This fMRI study analyzed activations for processing of word and colour, which were presented in each of the four quadrants, to investigate anatomical segregation between colour and orientation processing and also to examine the effect of visual stimulus position on brain activations. Main effect of visual category was found in the bilateral extrastriate cortices extending to the left visual word form area (word > colour) and small area of the right ventrolateral prefrontal cortex (colour > word). ROI analysis showed that there was a tendency that V4α, not V4/8, showed a greater response to colours than to words. Main effect of visual fields was found in early visual areas, which showed greater responses to the left than to the right field stimuli and also to the lower than to the upper field stimuli. No significant interactions between visual category and visual fields were found.

症例は80歳の男性．頸部回旋後に後頸部痛，右上下肢の麻痺，しびれ感，顔面の感覚鈍麻，喋りづらさがあり，当初，原因として椎骨動脈解離による脳梗塞が強く疑われた．しかし，発症14時間後の頭部MRIで責任病巣を認めず，「顔面の感覚鈍麻」と「喋りづらさ」を神経脱落徴候ではないと判断し，頸髄レベルの病変を疑い，頸部MRIで頸髄硬膜外血腫と診断した．顔面感覚鈍麻の訴えは変動し信頼性に乏しく，喋りづらさは口腔内乾燥によるものであった．脳卒中の疑われる患者が頭痛・頸部痛を訴える場合，稀だが治療が全く異なる頸髄・頸胸髄硬膜外血腫の可能性も念頭におきつつ，正確な神経学的部位診断・鑑別を心がけるべきである．

Physiological high frequency activities (HFA) are related to various brain functions. Factors, however, regulating its frequency have not been well elucidated in humans. To validate the hypothesis that different propagation modes (thalamo-cortical vs. cortico-coritcal projections), or different terminal layers (layer IV vs. layer II/III) affect its frequency, we, in the primary somatosensory cortex (SI), compared HFAs induced by median nerve stimulation with those induced by electrical stimulation of the cortex connecting to SI. We employed 6 patients who underwent chronic subdural electrode implantation for presurgical evaluation. We evaluated the HFA power values in reference to the baseline overriding N20 (earliest cortical response) and N80 (late response) of somatosensory evoked potentials (HFA(SEP(N20)) and HFA(SEP(N80))) and compared those overriding N1 and N2 (first and second responses) of cortico-cortical evoked potentials (HFA(CCEP(N1)) and HFA(CCEP(N2))). HFA(SEP(N20)) showed the power peak in the frequency above 200 Hz, while HFA(CCEP(N1)) had its power peak in the frequency below 200 Hz. Different propagation modes and/or different terminal layers seemed to determine HFA frequency. Since HFA(CCEP(N1)) and HFA induced during various brain functions share a similar broadband profile of the power spectrum, cortico-coritcal horizontal propagation seems to represent common mode of neural transmission for processing these functions.

Sleep‐induced changes in human brain connectivity/excitability and their physiologic basis remain unclear, especially in the frontal lobe. We investigated sleep‐induced connectivity and excitability changes in 11 patients who underwent chronic implantation of subdural electrodes for epilepsy surgery. Single‐pulse electrical stimuli were directly injected to a part of the cortices, and cortico‐cortical evoked potentials (CCEPs) and CCEP‐related high‐gamma activities (HGA: 100–200 Hz) were recorded from adjacent and remote cortices as proxies of effective connectivity and induced neuronal activity, respectively. HGA power during the initial CCEP component (N1) correlated with the N1 size itself across all states investigated. The degree of cortical connectivity and excitability changed during sleep depending on sleep stage, approximately showing dichotomy of awake vs. non‐rapid eye movement (REM) [NREM] sleep. On the other hand, REM sleep partly had properties of both awake and NREM sleep, placing itself in the intermediate state between them. Compared with the awake state, single‐pulse stimulation especially during NREM sleep induced increased connectivity (N1 size) and neuronal excitability (HGA increase at N1), which was immediately followed by intense inhibition (HGA decrease). The HGA decrease was temporally followed by the N2 peak (the second CCEP component), and then by HGA re‐increase during sleep across all lobes. This HGA rebound or re‐increase of neuronal synchrony was largest in the frontal lobe compared with the other lobes. These properties of sleep‐induced changes of the cortex may be related to unconsciousness during sleep and frequent nocturnal seizures in frontal lobe epilepsy. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc.

“Formes frustes” of encephalopathy associated with anti-NMDAR antibody have been recently described in cases of chronic epilepsy. We report a young woman with a parietal lesion and anti-NMDAR antibody who acquired bilateral, secondary epileptogenesis in the temporal lobes within a period as short as six years. Removal of the primary epileptogenic lesion of oligoastrocytoma in the right parietal lobe resulted in seizure freedom, disappearance of secondary foci, and substantial decrease of the antibody titre. Chronic exposure to anti-NMDAR antibody, albeit at a low titre, may have resulted in a smoldering chronic course and relatively early acquisition of “reversible” secondary foci without development of a high degree of epileptogenicity and structural changes.

The superior parietal lobule (SPL) and the medial parietal cortex are associated with integration of various kinds of information. Little is known about connections from the superior and medial parietal cortices in humans. Our objective is to delineate their connectivity by means of cortico-cortical evoked potential (CCEP). Subjects were eight patients who underwent chronic subdural electrode placement covering the dorso-lateral (SPL) or medial parietal cortices. Single-pulse electrical stimuli were delivered and CCEPs were obtained from the frontal and parietal areas by averaging electrocorticograms time-locked to stimuli. SPL stimulation elicited 75 CCEPs at the precuneus, precentral gyrus, the dorsal premotor area (dorsal PM). The precuneus elicited 66 CCEPs in the inferior parietal lobule (IPL), dorsal premotor area (PM) and SPL. The posterior cingulate cortex elicited 36 CCEPs at the middle cingulate cortex, SPL and the precuneus. This study demonstrated reciprocal connections between the superior and medial parietal cortices. While the precuneus tends to connect with the lateral frontal area, posterior cingulate cortex with medial frontal area. These findings would account for functional differentiation between these areas, and may help us understand seizure propagation in patients with parietal lobe epilepsy.

The preservation of language function during brain surgery still poses a challenge. No intraoperative methods have been established to monitor the language network reliably. We aimed to establish intraoperative language network monitoring by means of cortico‐cortical evoked potentials (CCEPs). Subjects were six patients with tumors located close to the arcuate fasciculus (AF) in the language‐dominant left hemisphere. Under general anesthesia, the anterior perisylvian language area (AL) was first defined by the CCEP connectivity patterns between the ventrolateral frontal and temporoparietal area, and also by presurgical neuroimaging findings. We then monitored the integrity of the language network by stimulating AL and by recording CCEPs from the posterior perisylvian language area (PL) consecutively during both general anesthesia and awake condition. High‐frequency electrical stimulation (ES) performed during awake craniotomy confirmed language function at AL in all six patients. Despite an amplitude decline (≤32%) in two patients, CCEP monitoring successfully prevented persistent language impairment. After tumor removal, single‐pulse ES was applied to the white matter tract beneath the floor of the removal cavity in five patients, in order to trace its connections into the language cortices. In three patients in whom high‐frequency ES of the white matter produced naming impairment, this “eloquent” subcortical site directly connected AL and PL, judging from the latencies and distributions of cortico‐ and subcortico‐cortical evoked potentials. In conclusion, this study provided the direct evidence that AL, PL, and AF constitute the dorsal language network. Intraoperative CCEP monitoring is clinically useful for evaluating the integrity of the language network. Hum Brain Mapp 35:4345–4361, 2014. © 2014 Wiley Periodicals, Inc.

We report a patient with prolonged monoparesis and parietal periodic lateralised epileptiform discharges (PLEDs). The patient was a 73-year-old man with chronic myelomonocytic leukaemia who developed persisting monoparesis of the right arm, sensory aphasia, and finger agnosia, initially associated with focal clonic seizures. These neurological deficits remained for seven days without subsequent focal clonic seizures. The EEG showed left-sided PLEDs, maximal in the left occipito-parietal area. Ten days later, following phenytoin treatment, these symptoms suddenly improved and parietal PLEDs disappeared. Sustained PLEDs in the left parietal region may have been causally associated with ictal paresis in this patient.

Although cerebral venous thrombosis (CVT) is generally treated with anticoagulants, some patients have a poor prognosis. We report a 34-year-old woman who developed severe CVT with mental symptoms and intracerebral hemorrhage with central herniation. She had a hypercoagulable state accompanied by thyrotoxicosis. Aggressive medical therapies including unfractionated heparin, a mixture of concentrated glycerin and fructose, and intravenous administration of thiamazole, iohexol, and propranolol were ineffective. The patient was treated with plasma exchange (PE) two times, in addition to aggressive medical therapies. The neurologic symptoms and laboratory data including high levels of thyroid hormones began to improve soon after the first PE. Activated partial thromboplastin time was prolonged after PE although the heparin dose was not changed. After 6 months, her modified Rankin Scale score was 2. PE should be considered for severe CVT as a result of a hypercoagulable state accompanied by thyrotoxicosis, because it not only reduces thyroid hormones, but also might remove multiple prothrombotic factors.