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

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

ヒト左下前頭回における結合性勾配について―術中皮質刺激皮質誘発電位による研究

京都大学0048新制・課程博士博士(医学)甲第22693号医博第4637号新制||医||1045(附属図書館)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 林 康紀, 教授 伊佐 正学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

The dynamics of cortical interactions in visual recognition of object category: living versus nonliving

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

PCR-Based Simple Subgrouping Is Validated for Classification of Gliomas and Defines Negative Prognostic Copy Number Aberrations in IDH Mutant Gliomas.

Genetic subgrouping of gliomas has been emphasized recently, particularly after the finding of isocitrate dehydrogenase 1 (IDH1) mutations. In a previous study, we investigated whole-chromosome copy number aberrations (CNAs) of gliomas and have described genetic subgrouping based on CNAs and IDH1 mutations. Subsequently, we classified gliomas using simple polymerase chain reaction (PCR)-based methods to improve the availability of genetic subgrouping. We selected IDH1/2 and TP53 as markers and analyzed 237 adult supratentorial gliomas using Sanger sequencing. Using these markers, we classified gliomas into three subgroups that were strongly associated with patient prognoses. These included IDH mutant gliomas without TP53 mutations, IDH mutant gliomas with TP53 mutations, and IDH wild-type gliomas. IDH mutant gliomas without TP53 mutations, which mostly corresponded to gliomas carrying 1p19q co-deletions, showed lower recurrence rates than the other 2 groups. In the other high-recurrence groups, the median progression-free survival (PFS) and overall survival (OS) of patients with IDH mutant gliomas with TP53 mutations were significantly longer than those of patients with IDH wild-type gliomas. Notably, most IDH mutant gliomas with TP53 mutations had at least one of the CNAs +7q, +8q, -9p, and -11p. Moreover, IDH mutant gliomas with at least one of these CNAs had a significantly worse prognosis than did other IDH mutant gliomas. PCR-based mutation analyses of IDH and TP53 were sufficient for simple genetic diagnosis of glioma that were strongly associated with prognosis of patients and enabled us to detect negative CNAs in IDH mutant gliomas