Persistent frequent subclinical seizures and memory impairment after clinical remission in smoldering limbic encephalitis.

Aim. To delineate a possible correlation between clinical course and EEG abnormalities in non-infectious “smoldering” limbic encephalitis. Methods. Long-term clinical data, including video-EEG monitoring records, were analysed in two patients. Results. The two patients were positive for anti-voltage-gated potassium channel complex antibody and unspecified antineuronal antibody, respectively. The latter patient had small cell lung carcinoma. Both patients had memory impairment and clinical seizures. EEG showed frequent subclinical seizure patterns in the bilateral temporal regions. Subclinical seizure patterns and memory impairment persisted over one to two years after clinical seizure remission. Therapy (prednisolone and chemoradiation in the two patients, respectively) resulted in decreased occurrence of subclinical seizure patterns and memory improvement. Conclusions. EEG seizure patterns may persist years after clinical seizure remission in “smoldering” limbic encephalitis and lead to memory impairment

Secondary motor areas for response inhibition: an epicortical recording and stimulation study

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 < 0.0001, effect size (d) = 0.30, Wilcoxon rank sum test], and increased No-Go error at some stimulation sites (25.0%: left posterior middle frontal gyrus and left pre-supplementary motor area). The stimulation sites we adopted for brief stimulation were most frequently labelled ‘negative motor area’ (63.6%), followed by ‘language-related area’ (18.2%) by the electrical cortical stimulation mapping. The stimulation sites where the brief stimulation increased No-Go errors tended to be labelled ‘language-related area’ more frequently than ‘negative motor area’ [P = 0.0833, Fisher’s exact test (two-sided)] and were located more anteriorly than were those without a No-Go error increase. By integrating the methods of different modality, namely, event-related potentials combined with brief stimulation and clinical electrical cortical stimulation mapping, we conducted a novel neuroscientific approach, providing direct evidence that secondary motor areas, especially the pre-supplementary motor area and posterior middle frontal gyrus, play an important role in response inhibition

Neural Sources of Vagus Nerve Stimulation–Induced Slow Cortical Potentials

[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

Evidence for a deep, distributed and dynamic code for animacy in human ventral anterior temporal cortex.

Funder: European Research Council; Grant(s): GAP: 502670428 - BRAIN2MIND_NEUROCOMPHow does the human brain encode semantic information about objects? This paper reconciles two seemingly contradictory views. The first proposes that local neural populations independently encode semantic features; the second, that semantic representations arise as a dynamic distributed code that changes radically with stimulus processing. Combining simulations with a well-known neural network model of semantic memory, multivariate pattern classification, and human electrocorticography, we find that both views are partially correct: information about the animacy of a depicted stimulus is distributed across ventral temporal cortex in a dynamic code possessing feature-like elements posteriorly but with elements that change rapidly and nonlinearly in anterior regions. This pattern is consistent with the view that anterior temporal lobes serve as a deep cross-modal 'hub' in an interactive semantic network, and more generally suggests that tertiary association cortices may adopt dynamic distributed codes difficult to detect with common brain imaging methods

Distinct connectivity patterns in human medial parietal cortices: Evidence from standardized connectivity map using cortico-cortical evoked potential

The medial parietal cortices are components of the default mode network (DMN), which are active in the resting state. The medial parietal cortices include the precuneus and the dorsal posterior cingulate cortex (dPCC). Few studies have mentioned differences in the connectivity in the medial parietal cortices, and these differences have not yet been precisely elucidated. Electrophysiological connectivity is essential for understanding cortical function or functional differences. Since little is known about electrophysiological connections from the medial parietal cortices in humans, we evaluated distinct connectivity patterns in the medial parietal cortices by constructing a standardized connectivity map using cortico-cortical evoked potential (CCEP). This study included nine patients with partial epilepsy or a brain tumor who underwent chronic intracranial electrode placement covering the medial parietal cortices. Single-pulse electrical stimuli were delivered to the medial parietal cortices (38 pairs of electrodes). Responses were standardized using the z-score of the baseline activity, and a response density map was constructed in the Montreal Neurological Institutes (MNI) space. The precuneus tended to connect with the inferior parietal lobule (IPL), the occipital cortex, superior parietal lobule (SPL), and the dorsal premotor area (PMd) (the four most active regions, in descending order), while the dPCC tended to connect to the middle cingulate cortex, SPL, precuneus, and IPL. The connectivity pattern differs significantly between the precuneus and dPCC stimulation (p<0.05). Regarding each part of the medial parietal cortices, the distributions of parts of CCEP responses resembled those of the functional connectivity database. Based on how the dPCC was connected to the medial frontal area, SPL, and IPL, its connectivity pattern could not be explained by DMN alone, but suggested a mixture of DMN and the frontoparietal cognitive network. These findings improve our understanding of the connectivity profile within the medial parietal cortices. The electrophysiological connectivity is the basis of propagation of electrical activities in patients with epilepsy. In addition, it helps us to better understand the epileptic network arising from the medial parietal cortices

Connectivity Gradient in the Human Left Inferior Frontal Gyrus: Intraoperative Cortico-Cortical Evoked Potential Study.

In the dual-stream model of language processing, the exact connectivity of the ventral stream to the anterior temporal lobe remains elusive. To investigate the connectivity between the inferior frontal gyrus (IFG) and the lateral part of the temporal and parietal lobes, we integrated spatiotemporal profiles of cortico-cortical evoked potentials (CCEPs) recorded intraoperatively in 14 patients who had undergone surgical resection for a brain tumor or epileptic focus. Four-dimensional visualization of the combined CCEP data showed that the pars opercularis (Broca's area) is connected to the posterior temporal cortices and the supramarginal gyrus, whereas the pars orbitalis is connected to the anterior lateral temporal cortices and angular gyrus. Quantitative topographical analysis of CCEP connectivity confirmed an anterior-posterior gradient of connectivity from IFG stimulus sites to the temporal response sites. Reciprocality analysis indicated that the anterior part of the IFG is bidirectionally connected to the temporal or parietal area. This study shows that each IFG subdivision has different connectivity to the temporal lobe with an anterior-posterior gradient and supports the classical connectivity concept of Dejerine; that is, the frontal lobe is connected to the temporal lobe through the arcuate fasciculus and also a double fan-shaped structure anchored at the limen insulae

Direct exploration of the role of the ventral anterior temporal lobe in semantic memory:Cortical stimulation and local field potential evidence from subdural grid electrodes

Semantic memory is a crucial higher cortical function that codes the meaning of objects and words, and when impaired after neurological damage, patients are left with significant disability. Investigations of semantic dementia have implicated the anterior temporal lobe (ATL) region, in general, as crucial for multimodal semantic memory. The potentially crucial role of the ventral ATL subregion has been emphasized by recent functional neuroimaging studies, but the necessity of this precise area has not been selectively tested. The implantation of subdural electrode grids over this subregion, for the presurgical assessment of patients with partial epilepsy or brain tumor, offers the dual yet rare opportunities to record cortical local field potentials while participants complete semantic tasks and to stimulate the functionally identified regions in the same participants to evaluate the necessity of these areas in semantic processing. Across 6 patients, and utilizing a variety of semantic assessments, we evaluated and confirmed that the anterior fusiform/inferior temporal gyrus is crucial in multimodal, receptive, and expressive, semantic processing

意味記憶に関する側頭葉底部前方領域の直接的検索：皮質電気刺激と硬膜下電極記録の局所電場電位からの証左

京都大学0048新制・課程博士博士(医学)甲第19272号医博第4036号新制||医||1011(附属図書館)32274京都大学大学院医学研究科医学専攻(主査)教授 高橋 淳, 教授 村井 俊哉, 教授 渡邉 大学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

Pre-SMA actively engages in conflict processing in human: A combined study of epicortical ERPs and direct cortical stimulation.

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 1-2cm 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