Speech decoding using cortical and subcortical electrophysiological signals.

Introduction: Language impairments often result from severe neurological disorders, driving the development of neural prosthetics utilizing electrophysiological signals to restore comprehensible language. Previous decoding efforts primarily focused on signals from the cerebral cortex, neglecting subcortical brain structures' potential contributions to speech decoding in brain-computer interfaces. Methods: In this study, stereotactic electroencephalography (sEEG) was employed to investigate subcortical structures' role in speech decoding. Two native Mandarin Chinese speakers, undergoing sEEG implantation for epilepsy treatment, participated. Participants read Chinese text, with 1-30, 30-70, and 70-150 Hz frequency band powers of sEEG signals extracted as key features. A deep learning model based on long short-term memory assessed the contribution of different brain structures to speech decoding, predicting consonant articulatory place, manner, and tone within single syllable. Results: Cortical signals excelled in articulatory place prediction (86.5% accuracy), while cortical and subcortical signals performed similarly for articulatory manner (51.5% vs. 51.7% accuracy). Subcortical signals provided superior tone prediction (58.3% accuracy). The superior temporal gyrus was consistently relevant in speech decoding for consonants and tone. Combining cortical and subcortical inputs yielded the highest prediction accuracy, especially for tone. Discussion: This study underscores the essential roles of both cortical and subcortical structures in different aspects of speech decoding.

Reduced-Reference Learning for Target Localization in Deep Brain Stimulation.

This work proposes a supervised machine learning method for target localization in deep brain stimulation (DBS). DBS is a recognized treatment for essential tremor. The effects of DBS significantly depend on the precise implantation of electrodes. Recent research on diffusion tensor imaging shows that the optimal target for essential tremor is related to the dentato-rubro-thalamic tract (DRTT), thus DRTT targeting has become a promising direction. The tractography-based targeting is more accurate than conventional ones, but still too complicated for clinical scenarios, where only structural magnetic resonance imaging (sMRI) data is available. In order to improve efficiency and utility, we consider target localization as a non-linear regression problem in a reduced-reference learning framework, and solve it with convolutional neural networks (CNNs). The proposed method is an efficient two-step framework, and consists of two image-based networks: one for classification and the other for localization. We model the basic workflow as an image retrieval process and define relevant performance metrics. Using DRTT as pseudo groundtruths, we show that individualized tractography-based optimal targets can be inferred from sMRI data with high accuracy. For two datasets of 280x220/272x227 (0.7/0.8 mm slice thickness) sMRI input, our model achieves an average posterior localization error of 2.3/1.2 mm, and a median of 1.7/1.02 mm. The proposed framework is a novel application of reduced-reference learning, and a first attempt to localize DRTT from sMRI. It significantly outperforms existing methods using 3D-CNN, anatomical and DRTT atlas, and may serve as a new baseline for general target localization problems.

Modeling and in vivo experimental validation of 1,064 nm laser interstitial thermal therapy on brain tissue.

Introduction: Laser interstitial thermal therapy (LITT) at 1064 nm is widely used to treat epilepsy and brain tumors; however, no numerical model exists that can predict the ablation region with careful in vivo validation. Methods: In this study, we proposed a model with a system of finite element methods simulating heat transfer inside the brain tissue, radiative transfer from the applicator into the brain tissue, and a model for tissue damage. Results: To speed up the computation for practical applications, we also validated P1-approximation as an efficient and fast method for calculating radiative transfer by comparing it with Monte Carlo simulation. Finally, we validated the proposed numerical model in vivo on six healthy canines and eight human patients with epilepsy and found strong agreement between the predicted temperature profile and ablation area and the magnetic resonance imaging-measured results. Discussion: Our results demonstrate the feasibility and reliability of the model in predicting the ablation area of 1,064 nm LITT, which is important for presurgical planning when using LITT.

ChatGPT's potential role in non-English-speaking outpatient clinic settings.

Researchers recently utilized ChatGPT as a tool for composing clinic letters, highlighting its ability to generate accurate and empathetic communications. Here we demonstrated the potential application of ChatGPT as a medical assistant in Mandarin Chinese-speaking outpatient clinics, aiming to improve patient satisfaction in high-patient volume settings. ChatGPT achieved an average score of 72.4% in the Chinese Medical Licensing Examination's Clinical Knowledge section, ranking within the top 20th percentile. It also demonstrated its potential for clinical communication in non-English speaking environments. Our study suggests that ChatGPT could serve as an interface between physicians and patients in Chinese-speaking outpatient settings, possibly extending to other languages. However, further optimization is required, including training on medical-specific datasets, rigorous testing, privacy compliance, integration with existing systems, user-friendly interfaces, and the development of guidelines for medical professionals. Controlled clinical trials and regulatory approval are necessary before widespread implementation. As chatbots' integration into medical practice becomes more feasible, rigorous early investigations and pilot studies can help mitigate potential risks.

Individualized targeting is warranted in subcallosal cingulate gyrus deep brain stimulation for treatment-resistant depression: A tractography analysis.

Subcallosal cingulate gyrus (SCG) is a target of deep brain stimulation (DBS) for treatment-resistant depression. However, previous randomized controlled trials report that approximately 42% of patients are responders to this therapy of last resort, and suboptimal targeting of SCG is a potential underlying factor to this unsatisfactory efficacy. Tractography has been proposed as a supplementary method to enhance targeting strategy. We performed a connectivity-based segmentation in the SCG region via probabilistic tractography in 100 healthy volunteers from the Human Connectome Project. The SCG voxels with maximum connectivity to brain regions implicated in depression, including Brodmann Area 10 (BA10), cingulate cortex, thalamus, and nucleus accumbens were identified, and the conjunctions were deemed as tractography-based targets. We then performed deterministic tractography using these targets in additional 100 volunteers to calculate streamline counts compassing to relevant brain regions and fibers. We also evaluated the intra- and inter-subject variance using test-retest dataset. Two tractography-based targets were identified. Tractography-based target-1 had the highest streamline counts to right BA10 and bilateral cingulate cortex, while tractography-based target-2 had the highest streamline counts to bilateral nucleus accumbens and uncinate fasciculus. The mean linear distance from individual tractography-based target to anatomy-based target was 3.2 ± 1.8 mm and 2.5 ± 1.4 mm in left and right hemispheres. The mean ± SD of targets between intra- and inter-subjects were 2.2 ± 1.2 and 2.9 ± 1.4 in left hemisphere, and 2.3 ± 1.4 and 3.1 ± 1.7 in right hemisphere, respectively. Individual heterogeneity as well as inherent variability from diffusion imaging should be taken into account during SCG-DBS target planning procedure.

Inhibition of TANK-binding kinase1 attenuates the astrocyte-mediated neuroinflammatory response through YAP signaling after spinal cord injury.

AIMS: TANK-binding kinase 1 (TBK1) is involved in regulating the pathological process of a variety of inflammatory diseases in the central nervous system. However, its role and underlying molecular mechanisms in spinal cord injury (SCI) remain largely unknown. METHODS: We employed the TBK1 inhibitor amlexanox (ALX) to address this question. An in vivo clip-compressive SCI model and in vitro lipopolysaccharide (LPS)-induced astrocyte inflammation model were established to examine the effects of TBK1 inhibition on the expression of proinflammatory cytokines. RESULTS: In this study, we found that TBK1 and TBK1-medicated innate immune pathways, such as TBK1/IRF3 and noncanonical NF-κB signaling, were activated in astrocytes and neurons after SCI. Furthermore, inhibition of TBK1 by ALX alleviated neuroinflammation response, reduced the loss of motor neurons, and improved the functional recovery after SCI. Mechanistically, inhibition of TBK1 activity promoted the activation of the noncanonical NF-κB signaling pathway and inhibited p-IRF3 activity in LPS-induced astrocytes, and the TBK1 activity was required for astrocytic activation through yes-associated protein (YAP) signaling after SCI and in LPS-induced astrocytes inflammation model. CONCLUSION: TBK1-medicated innate immune pathway in astrocytes through YAP signaling plays an important role in the pathogenesis of SCI and inhibition of TBK1 may be a potential therapeutic drug for SCI.

Deep Brain Stimulation for Advanced Parkinson Disease in Developing Countries: A Cost-Effectiveness Study From China.

BACKGROUND: The cost-effectiveness of deep brain stimulation (DBS) is more favorable than best medical treatment (BMT) for advanced Parkinson disease (PD) in developed countries. However, it remains unclear in developing countries, where the cost of DBS may not be reimbursed by health care system. OBJECTIVE: To model and evaluate the long-term cost-effectiveness of DBS for advanced PD in China from a patient payer perspective. METHODS: We developed a Markov model representing the clinical progress of PD to predict the disease progression and related medical costs in a 15-year time horizon. The incremental cost-effectiveness ratio (ICER) and net benefit were used to evaluate the cost-effectiveness of DBS vs BMT. RESULTS: DBS treatment led to discounted total costs of ¥370 768 ($56 515.20) (95% CI, ¥369 621.53-371 914.88), compared with ¥48 808 ($7439.68) (95% CI, ¥48 502.63-49 114.21) for BMT, with an additional 1.51 quality-adjusted life years gained, resulting in an ICER of ¥213 544 ($32 549.96)/quality-adjusted life years (95% CI, ¥208 177.35-218 910.10). Sensitivity analysis showed that DBS-related cost has the most substantial impact on ICER. Nation-wide net benefit of BMT and DBS were ¥33 819 ($5154.94) (95% CI, ¥30 211.24-37 426) and ¥30 361 ($4627.85) (95% CI, ¥25 587.03-39 433.66), respectively. Patient demographic analysis showed that more favorable DBS cost-effectiveness was associated with younger age and less severe disease stage. CONCLUSION: DBS is cost-effective for patients with advanced PD over a 15-year time horizon in China. However, compared with developed countries, DBS remains a substantial economic burden for patients when no reimbursement is provided. Our findings may help inform cost-effectiveness-based decision making for clinical care of PD in developing countries.

Long Non-coding RNA H19 Promotes NLRP3-Mediated Pyroptosis After Subarachnoid Hemorrhage in Rats.

NLRP3 inflammasomes have been reported to be an essential mediator in the inflammatory response during early brain injury (EBI) following subarachnoid hemorrhage (SAH). Recent studies have indicated that NLRP3 inflammasome-mediated pyroptosis and long non-coding RNA (lncRNA) H19 can participate in the inflammatory response. However, the roles and functions of lncRNA H19 in NLRP3 inflammasome-mediated pyroptosis during EBI after SAH are unknown and need to be further elucidated. NLRP3 inflammasome proteins were significantly elevated in CSF of human with SAH induced EBI and presented a positive correlation with severity. In ipsilateral hemisphere cortex of rats, these NLRP3 inflammasome proteins were also increased and accompanied with upregulation of H19, and both of NLRP3 and H19 were peaked at 24 h after SAH. However, knockdown of H19 markedly decreased the expression of NLRP3 inflammasome proteins at 24 h after SAH in rats and also ameliorated EBI, showing improved neurobehavioral deficits, cerebral edema, and neuronal injury. Moreover, knocking down of H19 downregulated the expression of Gasdermin D (GSDMD) in microglia in SAH rats. Similarly, knockdown of H19 also alleviated OxyHb-induced pyroptosis and NLRP3-mediated inflammasomes activation in primary microglia. Lastly, H19 competitively sponged with rno-miR-138-5p and then upregulated NLRP3 expression in the post-SAH inflammatory response. lncRNA H19 promotes NLRP3-mediated pyroptosis by functioning as rno-miR-138-5p sponge in rats during EBI after SAH, which might provide a potential therapeutic target for post-SAH inflammation regulation.

Evaluation of the knowledge, awareness, and attitudes toward epilepsy among nurses.

BACKGROUND: The standard of care provided to patients with chronic epilepsy might be affected by clinical nurses' understanding, awareness, and attitudes toward the condition. The objective of this study was to assess the knowledge, awareness, and attitudes toward chronic epilepsy among clinical nurses in the Second Affiliated Hospital of Zhejiang University School of Medicine, China. METHODS: Two hundred and thirty-eight nurses from the neurosurgery, neurology, epilepsy center, other internal medicine and other surgery department working at our hospital participated in this descriptive and cross-sectional study in 2022. The data were collected through an electronic questionnaire, which comprised four domains including demographic and clinical epilepsy-related questions, awareness of epilepsy section, 18 items for knowledge and a 15-item scale for attitudes. Mann-Whitney U tests, Kruskal-Wallis H tests, post hoc analysis, Pearson correlation analysis, and descriptive statistics were used to analyze the non-normal distribution of the dataset. RESULTS: The clinical nurses' average score on the awareness of epilepsy section was 14.93 ± 2.69 (maximum score: 20), the knowledge of epilepsy section scored 15.41 ± 2.30 (maximum score: 18), and the epilepsy attitude section scored 30.65 ± 7.40. The knowledge and awareness accuracy of the responses to the epilepsy-related questions were positively and significantly correlated (r = 0.251, p < 0.001). The multiple linear regression model found that the department (p < 0.001) and rank (p = 0.015) of nurses were independently associated with awareness toward epilepsy. Meanwhile, there was a statistically significant difference between the departments of nurses and accuracy on the Epilepsy Knowledge Scale (H = 18.340, p < 0.001). In addition, 92.77% of nurses agreed that people with chronic epilepsy have the same rights as all people. Unfortunately, over 30% of nurses maintained an uncertain attitude toward the employment, marriage, and emotion related to epilepsy. CONCLUSION: Our findings revealed that nurses had a general awareness and understanding of epilepsy, attitudes toward epilepsy. Specifically, nurses working in the Neurology Department and the Epilepsy Center were predisposed to have a considerably better level of awareness and knowledge of epilepsy. Additionally, as their understanding of epilepsy grew, so did their sensitivity to those who suffer from the condition. The study also recommends that epilepsy experts deliver additional lectures and training sessions to enhance nurses' knowledge of first-aid for seizures.

White Matter Tracts Associated With Deep Brain Stimulation Targets in Major Depressive Disorder: A Systematic Review.

Background: Deep brain stimulation (DBS) has been proposed as a last-resort treatment for major depressive disorder (MDD) and has shown potential antidepressant effects in multiple clinical trials. However, the clinical effects of DBS for MDD are inconsistent and suboptimal, with 30-70% responder rates. The currently used DBS targets for MDD are not individualized, which may account for suboptimal effect. Objective: We aim to review and summarize currently used DBS targets for MDD and relevant diffusion tensor imaging (DTI) studies. Methods: A literature search of the currently used DBS targets for MDD, including clinical trials, case reports and anatomy, was performed. We also performed a literature search on DTI studies in MDD. Results: A total of 95 studies are eligible for our review, including 51 DBS studies, and 44 DTI studies. There are 7 brain structures targeted for MDD DBS, and 9 white matter tracts with microstructural abnormalities reported in MDD. These DBS targets modulate different brain regions implicated in distinguished dysfunctional brain circuits, consistent with DTI findings in MDD. Conclusions: In this review, we propose a taxonomy of DBS targets for MDD. These results imply that clinical characteristics and white matter tracts abnormalities may serve as valuable supplements in future personalized DBS for MDD.

The Accuracy of Imaging Guided Targeting with Microelectrode Recoding in Subthalamic Nucleus for Parkinson's Disease: A Single-Center Experience.

BACKGROUND: Accurate electrode targeting was essential for the efficacy of deep brain stimulation (DBS). There is ongoing debate about the necessary of microelectrode recording (MER) in subthalamic nucleus (STN)-DBS surgery for accurate targeting. OBJECTIVE: This study aimed to analyze the accuracy of imaging-guided awake DBS with MER in STN for Parkinson's disease in a single center. METHODS: The authors performed a retrospective analysis of 161 Parkinson's disease patients undergoing STN-DBS at our center from March 2013 to June 2021. The implantation was performed by preoperative magnetic resonance imaging (MRI)-based direct targeting with intraoperative MER and macrostimulation testing. 285 electrode tracks with preoperative and postoperative coordinates were included to calculate the placement error in STN targeting. RESULTS: 85.9% of electrodes guided by preoperative MRI were implanted without intraoperative adjustment. 31 (10.2%) and 12 (3.9%) electrodes underwent intraoperative adjustment due to MER and intraoperative testing, respectively. We found 86.2% (245/285) of electrodes with trajectory error ≤2 mm. The MER physiological signals length < 4 mm and ≥4 mm group showed trajectory error > 2 mm in 38.0% and 8.8% of electrodes, respectively. Compared to non-adjustment electrodes, the final positioning of MER-adjusted electrodes deviated from the center of STN. CONCLUSION: The preoperative MRI guided STN targeting results in approximately 14% cases that require electrode repositioning. MER physiological signals length < 4 mm at first penetration implied deviation off planned target. MER combined with intraoperative awake testing served to rescue such deviation based on MRI alone.

On-Site Biolayer Interferometry-Based Biosensing of Carbamazepine in Whole Blood of Epileptic Patients.

On-site monitoring of carbamazepine (CBZ) that allows rapid, sensitive, automatic, and high-throughput detection directly from whole blood is of urgent demand in current clinical practice for precision medicine. Herein, we developed two types (being indirect vs. direct) of fiber-optic biolayer interferometry (FO-BLI) biosensors for on-site CBZ monitoring. The indirect FO-BLI biosensor preincubated samples with monoclonal antibodies towards CBZ (MA-CBZ), and the mixture competes with immobilized CBZ to bind towards MA-CBZ. The direct FO-BLI biosensor used sample CBZ and CBZ-horseradish peroxidase (CBZ-HRP) conjugate to directly compete for binding with immobilized MA-CBZ, followed by a metal precipitate 3,3'-diaminobenzidine to amplify the signals. Indirect FO-BLI detected CBZ within its therapeutic range and was regenerated up to 12 times with negligible baseline drift, but reported results in 25 min. However, Direct FO-BLI achieved CBZ detection in approximately 7.5 min, down to as low as 10 ng/mL, with good accuracy, specificity and negligible matric interference using a high-salt buffer. Validation of Direct FO-BLI using six paired sera and whole blood from epileptic patients showed excellent agreement with ultra-performance liquid chromatography. Being automated and able to achieve high throughput, Direct FO-BLI proved itself to be more effective for integration into the clinic by delivering CBZ values from whole blood within minutes.

Outcomes of Ventriculoperitoneal Shunt in Patients With Idiopathic Normal-Pressure Hydrocephalus 2 Years After Surgery.

Objective: To evaluate the outcomes and prognostic factors of ventriculoperitoneal shunts (VP-shunts) in patients with idiopathic normal-pressure hydrocephalus (iNPH) at 6 months and 2 years after surgery. Method: We retrospectively analyzed 68 patients admitted to our institute and diagnosed with probable iNPH from January 2017 to March 2021. All patients underwent VP-shunt surgery with a programmable valve, and their outcomes were assessed via the Krauss index and modified Rankin scale (mRS) at 6 months and 2 years post-surgery. Univariate and multivariate regression analysis was performed to identify the prognostic factors. Results: The mean age of the patients was 71.1 ± 8.4 (mean ± standard deviation) years. On the Krauss improvement index, 6-month follow-up results were available for 68 patients. Of these patients, 91.2% experienced attenuation of their preoperative symptoms, with a mean Krauss index of 0.58 ± 0.27, and 48 patients (70.6%) had a Krauss index ≥0.5. Two-year follow-up results were available for 33 patients; 90.9% of them had sustained improvement, with a Krauss index of 0.54 ± 0.31, and 21 patients (66.3%) had a Krauss index ≥0.5. Thirty-three patients (58%) were living independently after 2 years (mRS 0-2). The outcomes were worse for patients with multiple comorbidities. Neither an increased patient age nor a prolonged history of illness was statistically significant prognostic factors for adverse outcomes of VP-shunt surgery. Conclusion: Surgical treatment was well-tolerated by patients with iNPH who received VP-shunts. Most patients experienced attenuation of their preoperative symptoms. Multiple concurrent comorbidities should be considered as adverse prognostic factors before shunt insertion in patients with iNPH.

Ventriculosternal Shunt for the Treatment of Idiopathic Normal Pressure Hydrocephalus: A Case Report.

Background: Conventional corticospinal fluid (CSF) diversion surgery for idiopathic normal pressure hydrocephalus (iNPH) includes ventriculoperitoneal shunt and ventriculoatrial shunt. Ventriculosternal (VS) shunt may be considered if both the abdominal cavity and atrium are not feasible. Methods: A 76-year-old woman was admitted to our hospital with gait disturbance and urinary incontinence for 2 years, and the condition aggravated in the last 1 month. Based on clinical assessment and imaging findings, the patient was diagnosed with iNPH, with surgical indications. She was on peritoneal dialysis for chronic renal failure, and a cardiac Doppler echocardiogram showed enlargement of the left atrium and decreased diastolic function of the left ventricle. Due to these conditions, we chose the sternum as the vessel for CSF absorption and performed VS shunt. Results: No swelling, exudation, and effusion were found in the suprasternal fossa. Gait disturbance and urinary incontinence improved significantly immediately and 1 week after surgery, respectively. No shunt-related complication was reported at 16 months follow-up. Conclusion: This case demonstrated VS shunting as a feasible and alternative for the management of hydrocephalus.

A connectomic analysis of deep brain stimulation for treatment-resistant depression.

OBJECTIVE: Deep brain stimulation (DBS) has been used as a treatment of last resort for treatment-resistant depression (TRD) for more than a decade. Many DBS targets have been proposed and tested clinically, but the underlying circuit mechanisms remain unclear. Uncovering white matter tracts (WMT) activated by DBS targets may provide crucial information about the circuit substrates mediating DBS efficacy in ameliorating TRD. METHODS: We performed probabilistic tractography using diffusion magnetic resonance imaging datas from 100 healthy volunteers in Human Connectome Project datasets to analyze the structural connectivity patterns of stimulation targeting currently-used DBS target for TRD. We generated mean and binary fiber distribution maps and calculated the numbers of WMT streamlines in the dataset. RESULTS: Probabilistic tracking results revealed that activation of distinct DBS targets demonstrated modulation of overlapping but considerably distinct pathways. DBS targets were categorized into 4 groups: Cortical, Striatal, Thalamic, and Medial Forebrain Bundle according to their main modulated WMT and brain areas. Our data also revealed that Brodmann area 10 and amygdala are hub structures that are associated with all DBS targets. CONCLUSIONS: Our results together suggest that the distinct mechanism of DBS targets implies individualized target selection and formulation in the future of DBS treatment for TRD. The modulation of Brodmann area 10 and amygdala may be critical for the efficacy of DBS-mediated treatment of TRD.

Sylvian Fissure Meningiomas: Case Report and Literature Review.

Meningiomas are primary intracranial tumors derived from arachnoid cap cells or meningothelial cells and usually display dural attachment. However, a small proportion of meningiomas that arise from the Sylvian fissure do not manifest dural attachment. Sylvian fissure meningiomas are relatively rare and have differential characteristics as compared with typical meningiomas. Herein, we reported a special case of atypical meningioma in the Sylvian fissure, that showed non-enhancement after contract management. The patient was a 30-year-old woman with a 2-year history of seizures. Preoperative computerized tomography and magnetic resonance imaging scans showed a calcific, non-enhancing lesion in the right insula lobe. The lesion was excised surgically for seizure control. Intraoperatively, the tumor was observed to be closely adhered to the middle cerebral artery (MCA), resulting in mild arterial damage. A case of Sylvian fissure meningioma was ultimately diagnosed by histopathological examination of the resected specimens. Sylvian fissure meningiomas are closely associated with the MCA and exhibit unusual imaging characteristics. Preoperative misdiagnosis may have serious adverse consequences and may result in incorrect surgery. To improve awareness of Sylvian fissure meningiomas on the differential diagnosis of Sylvian fissure lesions among clinicians, we present this report and briefly summarize previously reported cases to describe the clinical, pathological, radiological, and surgical features.