Auditory prediction errors in sound frequency and duration generated different cortical activation patterns in the human brain: an ECoG study.

Sound frequency and duration are essential auditory components. The brain perceives deviations from the preceding sound context as prediction errors, allowing efficient reactions to the environment. Additionally, prediction error response to duration change is reduced in the initial stages of psychotic disorders. To compare the spatiotemporal profiles of responses to prediction errors, we conducted a human electrocorticography study with special attention to high gamma power in 13 participants who completed both frequency and duration oddball tasks. Remarkable activation in the bilateral superior temporal gyri in both the frequency and duration oddball tasks were observed, suggesting their association with prediction errors. However, the response to deviant stimuli in duration oddball task exhibited a second peak, which resulted in a bimodal response. Furthermore, deviant stimuli in frequency oddball task elicited a significant response in the inferior frontal gyrus that was not observed in duration oddball task. These spatiotemporal differences within the Parasylvian cortical network could account for our efficient reactions to changes in sound properties. The findings of this study may contribute to unveiling auditory processing and elucidating the pathophysiology of psychiatric disorders.

Auditory prediction and prediction error responses evoked through a novel cascade roving paradigm: a human ECoG study.

Auditory sensory processing is assumed to occur in a hierarchical structure including the primary auditory cortex (A1), superior temporal gyrus, and frontal areas. These areas are postulated to generate predictions for incoming stimuli, creating an internal model of the surrounding environment. Previous studies on mismatch negativity have indicated the involvement of the superior temporal gyrus in this processing, whereas reports have been mixed regarding the contribution of the frontal cortex. We designed a novel auditory paradigm, the "cascade roving" paradigm, which incorporated complex structures (cascade sequences) into a roving paradigm. We analyzed electrocorticography data from six patients with refractory epilepsy who passively listened to this novel auditory paradigm and detected responses to deviants mainly in the superior temporal gyrus and inferior frontal gyrus. Notably, the inferior frontal gyrus exhibited broader distribution and sustained duration of deviant-elicited responses, seemingly differing in spatio-temporal characteristics from the prediction error responses observed in the superior temporal gyrus, compared with conventional oddball paradigms performed on the same participants. Moreover, we observed that the deviant responses were enhanced through stimulus repetition in the high-gamma range mainly in the superior temporal gyrus. These features of the novel paradigm may aid in our understanding of auditory predictive coding.

Utilizing Excitatory and Inhibitory Activity Derived from Interictal Intracranial Electroencephalography as Potential Biomarkers for Epileptogenicity.

Epileptogenic zones (EZs), where epileptic seizures cease after resection, are localized by assessing the seizure-onset zone using ictal electroencephalography (EEG). Owing to the difficulty in capturing unpredictable seizures, biomarkers capable of identifying EZs from interictal EEG are anticipated. Recent studies using intracranial EEG have identified several potential candidate biomarkers for epileptogenicity. High-frequency oscillation (HFO) was initially expected to be a robust biomarker of abnormal excitatory activity in the ictogenic region. However, HFO-guided resection failed to improve seizure prognosis. Meanwhile, the regularity of low-gamma oscillations (30-80 Hz) indicates inhibitory interneurons' hypersynchronization, which could be used to localize the EZ. Besides resting-state EEG assessments, evoked potentials elicited by single-pulse electrical stimulation, such as corticocortical evoked potentials (CCEP), became valuable tools for assessing epileptogenic regions. CCEP responses recorded in the cortex remote from the stimulation site indicate functional connectivity, revealing increased internal connectivity within the ictogenic region and elevated inhibitory input from the non-involved regions to the ictogenic region. Conversely, large responses close to the stimulation site reflect local excitability, manifesting as an increased N1 amplitude and overriding HFO. Further research is required to establish whether these novel electrophysiological methods, either individually or in combination, can function as robust biomarkers of epileptogenicity and hold promise for improving seizure prognosis.

Paving the Way for Memory Enhancement: Development and Examination of a Neurofeedback System Targeting the Medial Temporal Lobe.

Neurofeedback (NF) shows promise in enhancing memory, but its application to the medial temporal lobe (MTL) still needs to be studied. Therefore, we aimed to develop an NF system for the memory function of the MTL and examine neural activity changes and memory task score changes through NF training. We created a memory NF system using intracranial electrodes to acquire and visualise the neural activity of the MTL during memory encoding. Twenty trials of a tug-of-war game per session were employed for NF and designed to control neural activity bidirectionally (Up/Down condition). NF training was conducted with three patients with drug-resistant epilepsy, and we observed an increasing difference in NF signal between conditions (Up-Down) as NF training progressed. Similarities and negative correlation tendencies between the transition of neural activity and the transition of memory function were also observed. Our findings demonstrate NF's potential to modulate MTL activity and memory encoding. Future research needs further improvements to the NF system to validate its effects on memory functions. Nonetheless, this study represents a crucial step in understanding NF's application to memory and provides valuable insights into developing more efficient memory enhancement strategies.

Intracranial Neurofeedback Modulating Neural Activity in the Mesial Temporal Lobe During Memory Encoding: A Pilot Study.

Removal of the mesial temporal lobe (MTL) is an established surgical procedure that leads to seizure freedom in patients with intractable MTL epilepsy; however, it carries the potential risk of memory damage. Neurofeedback (NF), which regulates brain function by converting brain activity into perceptible information and providing feedback, has attracted considerable attention in recent years for its potential as a novel complementary treatment for many neurological disorders. However, no research has attempted to artificially reorganize memory functions by applying NF before resective surgery to preserve memory functions. Thus, this study aimed (1) to construct a memory NF system that used intracranial electrodes to feedback neural activity on the language-dominant side of the MTL during memory encoding and (2) to verify whether neural activity and memory function in the MTL change with NF training. Two intractable epilepsy patients with implanted intracranial electrodes underwent at least five sessions of memory NF training to increase the theta power in the MTL. There was an increase in theta power and a decrease in fast beta and gamma powers in one of the patients in the late stage of memory NF sessions. NF signals were not correlated with memory function. Despite its limitations as a pilot study, to our best knowledge, this study is the first to report that intracranial NF may modulate neural activity in the MTL, which is involved in memory encoding. The findings provide important insights into the future development of NF systems for the artificial reorganization of memory functions.

Primary Intracranial Spindle Cell Sarcoma, DICER1-Mutant, with MDM2 Amplification Diagnosed on the Basis of Extensive Molecular Profiling.

Primary intracranial spindle cell sarcoma is an extremely rare mesenchymal tumor, the molecular pathogenesis of which is poorly understood. Because of the lack of specific markers, diagnosis sometimes relies on ruling out all possible differential diagnoses, often making it difficult to reach a definitive diagnosis. In this case study, we report a 69 year-old female patient for whom the integration of multi-layered molecular analyses contributed to making the diagnosis. The disease exhibited aggressive clinical behavior, requiring two sequential surgeries because of rapid regrowth within a short period. Primary and recurrent tumors exhibited similar histological features, in which spindle-shaped cells arranged in interlacing fascicles without any specific architectures, implicating sarcomatous tumors. In immunohistochemistry testing, tumor cells were immunopositive for vimentin but lacked any specific findings that contribute to narrowing down the differential diagnoses. Seeking further diagnostic clues, we performed DNA methylation-based analysis. The copy number analysis revealed MDM2 gene amplification and loss of heterozygosity of 22q. Moreover, dimension reduction clustering analysis implicated a methylation pattern comparable to aggressive types of sarcomas. In addition, an in-house next-generation sequencing panel ("Todai-OncoPanel") analysis identified somatic mutations in DICER1, NF2, and ATRX genes. Taken all together, we finally made the diagnosis of primary intracranial spindle cell sarcoma, DICER1-mutant, with MDM2 gene amplification. This case report suggests that even for the tumors with insufficient morphological and immuno-histological diagnostic clues, integration of multi-layered molecular analyses can contribute to making the diagnoses as well as to understanding the rare tumors by elucidating unexpected genetic and epigenetic features.

Spatiotemporal target selection for intracranial neural decoding of abstract and concrete semantics.

Decoding the inner representation of a word meaning from human cortical activity is a substantial challenge in the development of speech brain-machine interfaces (BMIs). The semantic aspect of speech is a novel target of speech decoding that may enable versatile communication platforms for individuals with impaired speech ability; however, there is a paucity of electrocorticography studies in this field. We decoded the semantic representation of a word from single-trial cortical activity during an imageability-based property identification task that required participants to discriminate between the abstract and concrete words. Using high gamma activity in the language-dominant hemisphere, a support vector machine classifier could discriminate the 2-word categories with significantly high accuracy (73.1 ± 7.5%). Activities in specific time components from two brain regions were identified as significant predictors of abstract and concrete dichotomy. Classification using these feature components revealed that comparable prediction accuracy could be obtained based on a spatiotemporally targeted decoding approach. Our study demonstrated that mental representations of abstract and concrete word processing could be decoded from cortical high gamma activities, and the coverage of implanted electrodes and time window of analysis could be successfully minimized. Our findings lay the foundation for the future development of semantic-based speech BMIs.

[Malignant Transformation of Cerebellopontine Angle Epidermoid Cyst:A Case Report].

Intracranial epidermoid cysts are benign cystic lesions that typically exhibit slow growth. Their malignant transformation into squamous cell carcinoma is rare. We report a 77-year-old woman who was admitted to our hospital because of a near-drowning incident due to a seizure sustained in her bathtub. Magnetic resonance imaging(MRI)revealed an extra-axial tumor occupying the right cerebellopontine angle. The lesion appeared hyperintense in diffusion-weighted images and exhibited contrast enhancement after gadolinium injection. Cerebrospinal fluid examination revealed noninfectious meningitis, presumably due to the ruptured epidermoid cyst. Tumor resection was performed and histopathological examination revealed squamous cell carcinoma, which was indicative of malignant transformation of the cyst. The patient underwent adjuvant radiotherapy and has no signs of recurrence 9 months postsurgery. Rapid neurological deterioration and contrast enhancement on MRI are key signs of malignant transformation of epidermoid cysts.

Resection of a lateral supratentorial endodermal cyst complicated by postoperative seizures: A case report.

BACKGROUND: Endodermal cysts are uncommon cystic lesions usually located at the ventral aspects of the spine. A lateral supratentorial location of such cysts is extremely rare. A unique case of a lateral supratentorial endodermal cyst that required surgical intervention due to uncal herniation, complicated with postoperative seizures, is presented. CASE DESCRIPTION: A 48-year-old man presented with transient motor aphasia and diplopia. Magnetic resonance imaging showed a cystic lesion occupying the left frontal and temporal convexity with midline shift and uncal herniation. Cyst resection was performed, and cyst contents with mucous-like components were aspirated. Histopathological examination showed an endodermal cyst. The patient showed no neurological deficits immediately after surgery but developed tonic-clonic seizures 9 h after surgery. Sedation and intubation were required to control the seizures. After administering multiple antiepileptic drugs, he was extubated on the 5th day after surgery. He was discharged home in a month with mild impairment in dexterity of his right hand. CONCLUSIONS: Surgical intervention for endodermal cysts can be complicated by postoperative seizures caused by chemical irritation of brain cortex due to spillage of cyst contents. It is important to irrigate the cyst wall very well intraoperatively and pay attention not to spill the cyst fluid to unaffected locations. Preoperative administration of antiepileptic drugs should also be considered if endodermal cysts, not simple arachnoid cysts, are suspected preoperatively.

Continuous production of d-lactic acid from cellobiose in cell recycle fermentation using ß-glucosidase-displaying Escherichia coli.

The present study demonstrates continuous production of d-lactic acid from cellobiose in a cell recycle fermentation with a hollow fiber membrane using recombinant Escherichia coli constructed by deleting its pyruvate formate-lyase activating enzyme gene pflA and expressing a heterologous ß-glucosidase on its cell surface. The ß-glucosidase gene bglC from Thermobifida fusca YX was cloned into a cell surface display vector pGV3, resulting in pGV3-bglC. Recombinant E. coli JM109 harboring the pGV3-bglC showed ß-glucosidase activity (18.9 ± 5.7 U/OD600), indicating the cell surface functioning of mutant ß-glucosidase. pH-stat cultivation using d-lactic acid producer E. coli BW25113 (ΔpflA) harboring pGV3-bglC in minimum medium with 10 g/L cellobiose in a jar fermentor under anaerobic condition resulted in 5.2 ± 0.1 g/L of d-lactic acid was obtained after 84 h cultivation, indicating that the engineered E. coli produced d-lactic acid directly from cellobiose. For continuous d-lactic acid production, cell recycle fermentation was conducted under anaerobic condition and the culture was continuously ultrafiltrated with a hollow fiber cartridge. The permeate was drawn to the reservoir and a minimum medium containing 10 g/L cellobiose was fed to the fermentor at the same rate (dilution rate, 0.05 h-1). Thus, this system maintained the d-lactic acid production (4.3-5.0 g/L), d-lactic acid production rate (0.22-0.25 g/L/h), and showed no residual cellobiose in the culture during 72 h operation. Interestingly, the d-lactic acid production rate in cell recycle fermentation was more than 3 times higher than that in the batch operation (0.06 ± 0.00 g/L/h).

Effects of repeated restraint and blood sampling with needle injection on blood cardiac troponins in rats, dogs, and cynomolgus monkeys.

While cardiac troponins (cTnT and cTnI) have been used as blood biomarkers of myocardial injury such as myocardial infarction in both humans and animals, their high diagnostic sensitivity inevitably leads to decreased diagnostic specificity. For example, it is difficult to judge whether a slight increase of cardiac troponins in toxicological studies is a treatment-related response or not. Drawing an accurate conclusion requires reliable background data and definitive criteria based on that data. However, no organized efforts in setting such criteria has been reported. Here, we measured blood cTnI and cTnT concentrations in Sprague-Dawley rats, beagle dogs, and cynomolgus monkeys from repeated blood samplings using needle cylinders under restraint up until 24 h after a single oral dose of 0.5 w/v% methyl cellulose solution as a vehicle. We revealed the extent of individual differences in baseline levels and operational effects. Our results can be useful in making criteria for judgment of treatment-related changes in cardiac troponins.

Challenges in the production of itaconic acid by metabolically engineered Escherichia coli.

Metabolic engineering allows the production of a variety of high-value chemicals in heterologous hosts. For example, itaconic acid (IA) has been produced in several microorganisms, such as Escherichia coli, Aspergillus niger, and Synechocystis sp. through the expression of cis-aconitate decarboxylase gene (cad) from Aspergillus terreus. Recently, we showed that inactivation of the isocitrate dehydrogenase gene and overexpression of the aconitase gene dramatically enhanced the production levels of IA in E. coli expressing cad. Furthermore, we demonstrated that it is possible to produce IA directly from starch by engineered E. coli that additionally expresses the α-amylase gene from Streptococcus bovis. In this study, we sum up our findings regarding the challenges of IA production in E. coli.

Production of itaconic acid in Escherichia coli expressing recombinant α-amylase using starch as substrate.

Several studies on fermentative production of a vinyl monomer itaconic acid from hydrolyzed starch using Aspergillus terreus have been reported. Herein, we report itaconic acid production by Escherichia coli expressing recombinant α-amylase, using soluble starch as its sole carbon source. To express α-amylase in E. coli, we first constructed recombinant plasmids expressing α-amylases by using cell surface display technology derived from two amylolytic bacteria, Bacillus amyloliquefaciens NBRC 15535(T) and Streptococcus bovis NRIC 1535. The recombinant α-amylase from S. bovis (SBA) showed activity at 28°C, which is the optimal temperature for production of itaconic acid, while α-amylase from B. amyloliquefaciens displayed no noticeable activity. E. coli cells expressing SBA produced 0.15 g/L itaconic acid after 69 h cultivation under pH-stat conditions, using 1% starch as the sole carbon source. In fact, E. coli cells expressing SBA had similar growth rates when grown in the presence of 1% glucose or starch, thereby highlighting the expression of an active α-amylase that enabled utilization of starch to produce itaconic acid in E. coli.

Toxicity prediction from toxicogenomic data based on class association rule mining.

While the recent advent of new technologies in biology such as DNA microarray and next-generation sequencer has given researchers a large volume of data representing genome-wide biological responses, it is not necessarily easy to derive knowledge that is accurate and understandable at the same time. In this study, we applied the Classification Based on Association (CBA) algorithm, one of the class association rule mining techniques, to the TG-GATEs database, where both toxicogenomic and toxicological data of more than 150 compounds in rat and human are stored. We compared the generated classifiers between CBA and linear discriminant analysis (LDA) and showed that CBA is superior to LDA in terms of both predictive performances (accuracy: 83% for CBA vs. 75% for LDA, sensitivity: 82% for CBA vs. 72% for LDA, specificity: 85% for CBA vs. 75% for LDA) and interpretability.