Auditory contextual processing has been assumed to be based on a hierarchical structure consisting of the primary auditory cortex, superior temporal gyrus (STG), and frontal lobe. Recent invasive ...studies on mismatch negativity (MMN) have revealed functional segregation for auditory contextual processing such as neural adaptation in the primary auditory cortex and prediction in the frontal lobe. However, the role of the STG remains unclear. We obtained induced activity in the high gamma band as mismatch response (MMR), an electrocorticographic (ECoG) counterpart to scalp MMN, and the components of MMR by analyzing ECoG data from patients with refractory epilepsy in an auditory oddball task paradigm. We found that MMR localized mainly in the bilateral posterior STGs, and that deviance detection largely accounted for MMR. Furthermore, adaptation was identified in a limited number of electrodes on the superior temporal plane. Our findings reveal a mixed contribution of deviance detection and adaptation depending on location in the STG. Such spatial considerations could lead to further understanding of the pathophysiology of relevant psychiatric disorders.
Abstract
Gamma oscillations are physiological phenomena that reflect perception and cognition, and involve parvalbumin-positive γ-aminobutyric acid-ergic interneuron function. The auditory ...steady-state response (ASSR) is the most robust index for gamma oscillations, and it is impaired in patients with neuropsychiatric disorders such as schizophrenia and autism. Although ASSR reduction is known to vary in terms of frequency and time, the neural mechanisms are poorly understood. We obtained high-density electrocorticography recordings from a wide area of the cortex in 8 patients with refractory epilepsy. In an ASSR paradigm, click sounds were presented at frequencies of 20, 30, 40, 60, 80, 120, and 160 Hz. We performed time-frequency analyses and analyzed intertrial coherence, event-related spectral perturbation, and high-gamma oscillations. We demonstrate that the ASSR is globally distributed among the temporal, parietal, and frontal cortices. The ASSR was composed of time-dependent neural subcircuits differing in frequency tuning. Importantly, the frequency tuning characteristics of the late-latency ASSR varied between the temporal/frontal and parietal cortex, suggestive of differentiation along parallel auditory pathways. This large-scale survey of the cortical ASSR could serve as a foundation for future studies of the ASSR in patients with neuropsychiatric disorders.
Reactive oxygen species (ROS) are involved in several cell death processes, including cerebral ischemic injury. We found that glutamate-induced ROS accumulation and the associated cell death in mouse ...hippocampal cell lines were delayed by pharmacological inhibition of autophagy or lysosomal activity. Glutamate, however, did not stimulate autophagy, which was assessed by a protein marker, LC3, and neither changes in organization of mitochondria nor lysosomal membrane permeabilization were observed. Fluorescent analyses by a redox probe PF-H2TMRos revealed that autophagosomes and/or lysosomes are the major sites for basal ROS generation in addition to mitochondria. Treatments with inhibitors for autophagy and lysosomes decreased their basal ROS production and caused a burst of mitochondrial ROS to be delayed. On the other hand, attenuation of mitochondrial activity by serum depletion or by high cell density culture resulted in the loss of both constitutive ROS production and an ROS burst in mitochondria. Thus, constitutive ROS production within mitochondria and lysosomes enables cells to be susceptible to glutamate-induced oxidative cytotoxicity. Likewise, inhibitors for autophagy and lysosomes reduced neural cell death in an ischemia model in rats. We suggest that cell injury during periods of ischemia is regulated by ROS-generating activity in autophagosomes and/or lysosomes as well as in mitochondria.
Introduction
Germ cell tumors (GCTs) are uncommon neoplasms predominantly arising in midline tissues. The prognostic significance of histopathology in predicting metastatic GCT behavior is poorly ...understood.
Methods
Multicenter international cohort study including 29 patients with GCTs metastatic to brain were retrospectively investigated (18 patients from Mayo Clinic and 11 patients from the intracranial germ cell tumor genome analysis consortium in Japan). Clinical characteristics were analyzed using the Chi-square test (two-tailed) for categorical variables and using the log-rank test for survival data.
Results
Median age at treatment was 31 years (range 14–58). Primary disease sites were testis (71%), mediastinum (18%), and female reproductive organs (11%). Median metastatic interval was 223 days (range, 6–6124). Median follow-up was 346 days (range, 1–5356), with 16 deaths (57%) occurring after the median overall survival of 455 days. Actuarial one-year survival was 51%; 12-of-16 deaths (75%) were attributed to intracranial disease. Appearance of the same GCT subtype at the metastatic site as the primary was high for non-seminomatous GCT (NSGCT, 64–100%), but low for seminoma/dysgerminoma and mature teratoma (MT, 14, 17%, respectively). Gain of a new component was seen in 4 (20%)—3 of which included embryonal carcinoma (EC) at the primary site (75%). Incidence of cases without seminoma/dysgerminoma increased significantly after metastasis (p = 0.02). Metastatic interval was shorter in cases with histological change (199 vs 454 days, p = 0.009). Overall survival was associated with MT primary histopathology (p = 0.02).
Conclusion
Histological differentiation at the primary GCT site influences metastatic prognosis. Aggressive behavior is associated with NSGCT, while EC frequently demonstrates multi-directional histological differentiation after brain metastasis, and such histological dynamism is associated with shorter metastatic interval. Most metastases occurred within one year of diagnosis, emphasizing the need for close surveillance in newly diagnosed extra-cranial GCT.
We integrated clinical, histopathological, and molecular data of central nervous system germ cell tumors to provide insights into their management.
Data from the Intracranial Germ Cell Tumor Genome ...Analysis (iGCT) Consortium were reviewed. A total of 190 cases were classified as primary germ cell tumors (GCTs) based on central pathological reviews.
All but one of the cases that were bifocal (neurohypophysis and pineal glands) and cases with multiple lesions including neurohypophysis or pineal gland were germinomas (34 of 35). Age was significantly higher in patients with germinoma than other histologies. Comparison between tumor marker and histopathological diagnoses showed that 18.2% of histopathologically diagnosed germinomas were marker positive and 6.1% of non-germinomatous GCTs were marker negative, suggesting a limitation in the utility of markers or histopathology alone using small specimens for diagnosis. Comparison between local and central histopathological diagnoses revealed a discordance of 12.7%. Discordance was significantly less frequent in biopsy cases, implying difficulty in detecting all histopathological components of heterogeneous GCTs. Germinomas at the typical sites (neurohypophysis or pineal gland) showed a better progression-free survival than those at atypical sites (P = 0.03). A molecular clinical association study revealed frequent mitogen-activated protein kinase (MAPK) pathway mutations in males (51.4% vs 14.3%, P = 0.007), and phosphatidylinositol-3 kinase/mammalian target of rapamycin (PI3K/mTOR) pathway mutations in basal ganglia cases (P = 0.004). Basal ganglia cases also had frequent chromosomal losses. Some chromosomal aberrations (2q, 8q gain, 5q, 9p/q, 13q, 15q loss) showed potential prognostic significance.
The in-depth findings of this study regarding clinical and molecular heterogeneity will increase our understanding of the pathogenesis of this enigmatic tumor.
The treatment for middle cerebral artery subocclusive thrombi is not standardized. Here, we report a case of M1 subocclusive thrombus with lateral lenticulostriate artery occlusion that was ...successfully treated with mechanical thrombectomy. This article describes a treatment strategy for M1 subocclusive thrombus, focusing on the indications for mechanical thrombectomy. A 58-year-old male on admission for pneumonia had a sudden onset of dysarthria and motor deficits. He has a history of dilated cardiomyopathy and underwent left ventricular assist device implantation 3 years ago. At onset, his National Institutes of Health Stroke Scale (NIHSS) score was nine. Computed tomography angiography demonstrated a filling defect in the distal right M1 segment of the middle cerebral artery. Angiography confirmed the presence of a subocclusive thrombus within the distal right M1 segment, although peripheral blood flow was maintained. Mechanical thrombectomy was performed for the M1 subocclusive thrombus using a direct aspiration first-pass technique, resulting in successful aspiration of the thrombus on the first pass. After the procedure, recanalization of the lateral lenticulostriate artery was detected, and the patient demonstrated full recovery (NIHSS score 0). Mechanical thrombectomy can be considered as a treatment option in cases of acute ischemic stroke caused by M1 subocclusive thrombus with lateral lenticulostriate artery occlusion, which presents with a high NIHSS score or neurological deterioration.
A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA) indicated the superiority of medical management in reducing the risks for strokes and other neurological deficits over ...observation alone. The aim of our study was to verify the rationale for stereotactic radiosurgery (SRS) for small unruptured arteriovenous malformation.
A retrospective review was performed for 292 patients with unruptured arteriovenous malformations referred for SRS. The risks for cerebral hemorrhages were statistically compared before and after SRS.
Of the 292 patients in whom arteriovenous malformation was found unruptured at initial diagnosis, 17 sustained hemorrhages in the period between the diagnosis and the initial therapeutic intervention (annual bleeding rate, 2.1%; 95% confidence interval CI, 1.2%-3.4%). Of the remaining 275 patients, 240 were initially treated with SRS, and 16 sustained a hemorrhage after SRS (annual bleeding rate, 1.1%; 95% CI, 0.6%-1.8%), but only 2 sustained a hemorrhage after angiographic obliteration (annual bleeding rate, 0.3%; 95% CI, 0.04%-1.2%). Comparing the risk of hemorrhage between the periods before and after SRS, a 53% risk reduction was achieved after SRS (hazard ratio, 0.47; 95% CI, 0.24-0.94; P=0.03), and 85% reduction was achieved after angiographic obliteration (hazard ratio, 0.15; 95% CI, 0.02-0.53; P=0.002).
SRS can significantly reduce the risk of stroke in the patients with small unruptured arteriovenous malformations. To definitively determine the clinical benefits of SRS, a longer follow-up will be necessary. However, based on our results, we can recommend SRS for patients who face a latent risk for stroke from this intractable vascular disease.
Purpose
It is often time-consuming to segment fine structures, such as the cerebral arteries from magnetic resonance imaging (MRI). Moreover, extracting anatomically abnormal structures is generally ...difficult. The segmentation workflow called threshold field painting was tested for its feasibility in morbid minute artery segmentation with special emphasis on time efficiency.
Methods
Seven patients with meningioma with ten-sided feeding arteries (
n
= 10) originating from middle meningeal arteries (MMA) were investigated by three experts of the conventional method for segmentation. The MRI time-of-flight sequence was utilized for the segmentation of each procedure. The tasks were accomplished using both the conventional method and the proposed method in random order. The task completion time and usability score were analyzed using the Wilcoxon signed-rank test.
Results
Except for one examinee (
P
= 0.06), the completion time significantly decreased (both
P
< 0.01) with the use of the proposed method. The average task completion time among the three examinees for the conventional method was 2.8 times longer than that for the proposed method. The usability score was generally in favor of the proposed method.
Conclusion
The normally nonexistent minute arteries, such as the MMA feeders, were deemed more efficiently segmented with the proposed method than with the conventional method. While automatic segmentation might be the ultimate solution, our semiautomatic method incorporating expert knowledge is expected to work as the practical solution.
Five-aminolevulinic acid (5-ALA) is widely used as an intraoperative fluorescent probe for radical resection of high-grade glioma, and thus aids in extending progression-free survival of patients. ...However, there exist some cases where 5-ALA fails to fluoresce. In some other cases, it may undergo fluorescence quenching but cannot be orally readministered during surgery. This study aimed to develop a novel hydroxymethyl rhodamine green (HMRG)-based fluorescence labeling system that can be repeatedly administered as a topical spray during surgery for the detection of glioblastoma.
We performed a three-stage probe screening using tumor lysates and fresh tumor tissues with our probe library consisting of a variety of HMRG probes with different dipeptides. We then performed proteome and transcript expression analyses to detect candidate enzymes responsible for cleaving the probe. Moreover,
and
studies using U87 glioblastoma cell line were conducted to validate the findings.
The probe screening identified proline-arginine-HMRG (PR-HMRG) as the optimal probe that distinguished tumors from peritumoral tissues. Proteome analysis identified calpain-1 (
to be responsible for cleaving the probe.
was highly expressed in tumor tissues which reacted to the PR-HMRG probe. Knockdown of this enzyme suppressed fluorescence intensity in U87 glioblastoma cells.
assay using a mouse U87 xenograft model demonstrated marked contrast of fluorescence with the probe between the tumor and peritumoral tissues.
The novel fluorescent probe PR-HMRG is effective in detecting glioblastoma when applied topically. Further investigations are warranted to assess the efficacy and safety of its clinical use.
Lacrimal gland pleomorphic adenomas (LGPAs) are common, benign, and intraorbital tumours that cause exophthalmos, ptosis, and visual disturbances. The curative treatment for LGPAs is gross total ...resection, and radiotherapy is considered adjunctive for recurrence or an alternative for inoperable LGPAs. Stereotactic radiosurgery (SRS) can be used for precise delivery of high radiation doses to the tumour, crucial in the treatment of intra-and extracranial neoplasms. Here, we present a 95-year-old woman who had a rapidly growing, recurrent LGPA and was successfully treated with SRS. The tumour was controlled without any adverse events over 21 months following SRS. SRS is a potential alternative treatment for recurrent LGPA.
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