The Effectiveness of Transcranial Magnetic Stimulation (TMS) Paradigms as Treatment Options for Recovery of Language Deficits in Chronic Poststroke Aphasia

Background. In an effort to boost aphasia recovery, modern rehabilitation, in addition to speech and language therapy (SALT), is increasingly incorporating noninvasive methods of brain stimulation. The present study is aimed at investigating the effectiveness of two paradigms of neuronavigated repetitive transcranial magnetic stimulation (rTMS): (i) 1 Hz rTMS and (ii) continuous theta burst stimulation (cTBS) each as a standalone treatment for chronic aphasia poststroke. Methods. A single subject experimental design (SSED) trial was carried out in which six people with aphasia (PWA) were recruited, following a single left hemispheric stroke more than six months prior to the study. Three individuals were treated with 1 Hz rTMS, and the remaining three were treated with cTBS. In all cases, TMS was applied over the right pars triangularis (pTr). Language assessment, with standardized and functional measures, and cognitive evaluations were carried out at four time points: twice prior to treatment (baseline), one day immediately posttreatment, and at follow-up two months after treatment was terminated. Quality of life (QoL) was also assessed at baseline and two months posttreatment. In addition, one of the participants with severe global aphasia was followed up again one and two years posttherapy. Results. For all participants, both rTMS paradigms (1 Hz rTMS and cTBS) generated trends towards improvement in several language skills (i.e., verbal receptive language, expressive language, and naming and reading) one day after treatment and/or two months after therapy. Rated QoL remained stable in three individuals, but for the other three, the communication scores of the QoL were reduced, while two of them also showed a decline in the psychological scores. The participant that was treated with cTBS and followed for up to two years showed that the significant improvement she had initially exhibited in comprehension and reading skills two months after TMS (1st follow-up) was sustained for at least up to two years. Conclusion. From the current findings, it is suggested that inhibitory TMS over the right pTr has the potential to drive neuroplastic changes as a standalone treatment that facilitates language recovery in poststroke aphasia.

Initial Clinical Experience of Repeat Thrombectomy with a Retrieval Stent (RTRS) with Continuous Proximal Flow Arrest by Balloon Guide Catheter for Acute Intracranial Carotid Occlusion

Background. Balloon guide catheters (BGCs) have good performance in terms of radiological outcomes in acute ischemic thrombectomy. It is not uncommon for BGCs to be blocked by thrombi, especially in cases with acute intracranial internal carotid artery (ICA) occlusion. Our initial experience using repeat thrombectomy with a retrieval stent (RTRS) with continuous proximal flow arrest by BGC for acute intracranial ICA occlusion is presented. Methods. In patients with acute intracranial ICA occlusion treated with RTRS, clinical data, including the National Institutes of Health Stroke Scale (NIHSS) score at admission and modified Rankin Scale (mRS) score at 90 days, and procedural data, including the Extended treatment in Cerebral Infarction (eTICI) score, procedural time, and complications, were analyzed. Results. Thirty-two consecutive patients (12 men (37.5%); mean age: 73 years) were treated with RTRS using a BGC. The median NIHSS score was 19. The median puncture-to-reperfusion time was 46 minutes (range: 22-142 minutes). All patients were successfully revascularized; eTICI 2c or better recanalization was achieved in 30 (93.8%) patients. No procedure-related complications or symptomatic intracranial hemorrhage occurred. Two cases (6.3%) had distal emboli, but none had emboli to the anterior cerebral artery. Fourteen patients (43.8%) achieved a good outcome with an mRS score of 0–2 at 90 days, and 8 patients (25.0%) died. Conclusions. In patients with intracranial ICA occlusion, RTRS with proximal flow arrest by BGC is effective and safe, achieving good clinical and angiographic outcomes. This method may reduce the incidence of distal emboli in thrombectomy with stent retrievers.

The Parkinson’s Disease Progression Neuroimaging Initiative

The Parkinson’s Disease Progressive Neuroimaging Initiative (PDPNI) is a longitudinal observational clinical study. In PDPNI, the clinical and imaging data of patients diagnosed with Parkinsonian syndromes and Idiopathic rapid eye movement sleep behavior disorder (RBD) were longitudinally followed every two years, aiming to identify progression biomarkers of Parkinsonian syndromes through functional imaging modalities including FDG-PET, DAT-PET imaging, ASL MRI, and fMRI, as well as the treatment conditions, clinical symptoms, and clinical assessment results of patients. From February 2012 to March 2019, 224 subjects (including 48 healthy subjects and 176 patients with confirmed PDS) have been enrolled in PDPNI. The detailed clinical information and clinical assessment scores of all subjects were collected by neurologists from Huashan Hospital, Fudan University. All subjects enrolled in PDPNI were scanned with 18F-FDG PET, 11C-CFT PET, and MRI scan sequence. All data were collected in strict accordance with standardized data collection protocols.

A Rapid Artificial Intelligence-Based Computer-Aided Diagnosis System for COVID-19 Classification from CT Images

The excessive number of COVID-19 cases reported worldwide so far, supplemented by a high rate of false alarms in its diagnosis using the conventional polymerase chain reaction method, has led to an increased number of high-resolution computed tomography (CT) examinations conducted. The manual inspection of the latter, besides being slow, is susceptible to human errors, especially because of an uncanny resemblance between the CT scans of COVID-19 and those of pneumonia, and therefore demands a proportional increase in the number of expert radiologists. Artificial intelligence-based computer-aided diagnosis of COVID-19 using the CT scans has been recently coined, which has proven its effectiveness in terms of accuracy and computation time. In this work, a similar framework for classification of COVID-19 using CT scans is proposed. The proposed method includes four core steps: (i) preparing a database of three different classes such as COVID-19, pneumonia, and normal; (ii) modifying three pretrained deep learning models such as VGG16, ResNet50, and ResNet101 for the classification of COVID-19-positive scans; (iii) proposing an activation function and improving the firefly algorithm for feature selection; and (iv) fusing optimal selected features using descending order serial approach and classifying using multiclass supervised learning algorithms. We demonstrate that once this method is performed on a publicly available dataset, this system attains an improved accuracy of 97.9% and the computational time is almost 34 (sec).

Therapeutic Application of rTMS in Atypical Parkinsonian Disorders

The terms atypical parkinsonian disorders (APDs) and Parkinson plus syndromes are mainly used to describe the four major entities of sporadic neuronal multisystem degeneration: progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), multiple system atrophy (MSA), and dementia with Lewy bodies (LBD). APDs are characterized by a variety of symptoms and a lack of disease modifying therapies; their treatment thus remains mainly symptomatic. Brain stimulation via repetitive transcranial magnetic stimulation (rTMS) is a safe and noninvasive intervention using a magnetic coil, and it is considered an alternative therapy in various neuropsychiatric pathologies. In this paper, we review the available studies that investigate the efficacy of rTMS in the treatment of these APDs and Parkinson plus syndromes. Τhe majority of the studies have shown beneficial effects on motor and nonmotor symptoms, but research is still at a preliminary phase, with large, double-blind studies lacking in the literature.

Advances regarding Neuroinflammation Biomarkers with Noninvasive Techniques in Epilepsy

A rapidly growing body of evidence supports that neuroinflammation plays a major role in epileptogenesis and disease progression. The capacity to identify pathological neuroinflammation in individuals with epilepsy is a crucial step on the timing of anti-inflammatory intervention and patient selection, which will be challenging aspects in future clinical studies. The discovery of noninvasive biomarkers that are accessible in the blood or molecular neuroimaging would facilitate clinical translation of experimental findings into humans. These innovative and noninvasive approaches have the advantage of monitoring the dynamic changes of neuroinflammation in epilepsy. Here, we will review the available evidence for the measurement of neuroinflammation in patients with epilepsy using noninvasive techniques and critically analyze the major scientific challenges of noninvasive methods. Finally, we propose the potential for use in clinical applications.

Curcumin Relieves Chronic Unpredictable Mild Stress-Induced Depression-Like Behavior through the PGC-1α/FNDC5/BDNF Pathway

Background and Aim. Increasing evidence suggests that the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α)/fibronectin type III domain-containing 5 (FNDC5)/brain-derived neurotrophic factor (BDNF) pathway might be critical for neuroprotection. Our present study is aimed at investigating the antidepressant-like effects of curcumin (CUR) in a chronic unpredictable mild stress- (CUMS-) induced depression rat model and explore whether the PGC-1α/FNDC5/BDNF pathway is the major driving force behind the therapeutic effects of CUR. Methods. All rats were randomly divided into four groups, namely, control, CUMS, CUMS + CUR , and CUMS + CUR + SR 18292 (PGC-1α inhibitor). Behavioral tests were conducted to assess the antidepressant-like effects of CUR. The expressions of PGC-1α, estrogen-related receptor alpha (ERRα), FNDC5, and BDNF were determined to investigate the regulatory effects of CUR on the PGC-1α/FNDC5/BDNF pathway. The PGC-1α inhibitor SR18292 was used to explore the role of PGC-1α in the induction of BDNF by CUR. Results. Daily gavage of 100 mg/kg CUR successfully attenuated the abnormal behaviors induced by CUMS and effectively prevented CUMS-induced reduction of PGC-1α, ERRα, FNDC5, and BDNF expressions. CUR also enhanced PGC-1α and ERRα translocation from cytoplasm to nucleus. Furthermore, we found that CUR supplementation effectively promoted neurocyte proliferation and suppressed neuronal apoptosis induced by CUMS. Of note, the PGC-1α inhibitor SR18292 remarkably reversed the beneficial effects of CUR on depressed rats, indicating an important role of PGC-1α in the antidepressant-like effects of CUR. Conclusion. Collectively, our data evaluating the neuroprotective action of CUR in the CUMS rats highlights the involvement of the PGC-1α/FNDC5/BDNF pathway in the antidepressant-like effects of CUR.

Serum Glycoproteomics and Identification of Potential Mechanisms Underlying Alzheimer’s Disease

Objectives. This study compares glycoproteomes in Thai Alzheimer’s disease (AD) patients with those of cognitively normal individuals. Methods. Study participants included outpatients with clinically diagnosed AD ( N = 136 ) and healthy controls without cognitive impairment ( N = 183 ). Blood samples were collected from all participants for biochemical analysis and for Apolipoprotein E (APOE) genotyping by real-time TaqMan PCR assays. Comparative serum glycoproteomic profiling by liquid chromatography-tandem mass spectrometry was then performed to identify differentially abundant proteins with functional relevance. Results. Statistical differences in age, educational level, and APOE ɛ3/ɛ4 and ɛ4/ɛ4 haplotype frequencies were found between the AD and control groups. The frequency of the APOE ɛ4 allele was significantly higher in the AD group than in the control group. In total, 871 glycoproteins were identified, including 266 and 259 unique proteins in control and AD groups, respectively. There were 49 and 297 upregulated and downregulated glycoproteins, respectively, in AD samples compared with the controls. Unique AD glycoproteins were associated with numerous pathways, including Alzheimer’s disease-presenilin pathway (16.6%), inflammation pathway mediated by chemokine and cytokine signaling (9.2%), Wnt signaling pathway (8.2%), and apoptosis signaling pathway (6.7%). Conclusion. Functions and pathways associated with protein-protein interactions were identified in AD. Significant changes in these proteins can indicate the molecular mechanisms involved in the pathogenesis of AD, and they have the potential to serve as AD biomarkers. Such findings could allow us to better understand AD pathology.

Research Progress in Vitamin A and Autism Spectrum Disorder

Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder. Over the past few decades, many studies have investigated the effects of VA supplementation in ASD patients and the relationship between vitamin A (VA) levels and ASD. VA is an essential micronutrient that plays an important role in various systems and biological processes in the form of retinoic acid (RA). Recent studies have shown that serum VA concentration is negatively correlated with the severity of ASD. The lack of VA during pregnancy or early fetal development can affect brain development and lead to long-term or even permanent impairment in the learning process, memory formation, and cognitive function. In addition, VA deficiency has been reported to have a major impact on the gastrointestinal function of children with ASD, while VA supplementation has been shown to improve the symptoms of ASD to a certain extent. This paper provides a comprehensive review of the relationship between VA and ASD.

Solitary Nitric Oxide Signaling Mediates Mild Stress-Induced Anxiety and Norepinephrine Release in the Bed Nucleus of the Stria Terminalis during Protracted Ethanol Withdrawal

Ethanol withdrawal (EtOHW) alters the pattern of neurohormonal and behavioral response toward internal and external stimuli, which mediates relapse to alcohol use even after a long period of abstinence. Increased noradrenergic signaling from the nucleus tractus solitarius (NTS) to the bed nucleus of the stria terminalis (BNST) during EtOHW underlies withdrawal-induced anxiety, while nitric oxide synthase (NOS) inhibitors injected into the periaqueductal area attenuate EtOHW-induced anxiety. Therefore, this study investigated the involvement of NOS within the NTS in anxiety and increased norepinephrine (NE) release in the BNST during protracted EtOHW in rats exposed to a mild stress. Rats were intraperitoneally administered 3 g/kg/day EtOH for 21 days followed by 28 days of withdrawal, and on the 28th day of withdrawal, the rats were subjected to restraint stress for 7 minutes. The elevated plus maze test was employed to evaluate anxiety-like behavior in rats, and in vivo microdialysis was used to measure the extracellular NE level in the BNST. In elevated plus maze tests, EtOHW rats but not EtOH-naive rats exhibited anxiety-like behavior when challenged with 7-minute mild restraint stress, which was, respectively, mitigated by prior intra-NTS infusion of the nitric oxide scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (carboxy-PTIO), nonselective NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME), or selective neuronal NOS (nNOS) inhibitor 7-nitroindazole (7-NI). Each of these agents also decreased the plasma corticosterone levels in EtOHW rats. In in vivo microdialysis, prior intra-NTS infusion of carboxy-PTIO, L-NAME, or 7-NI attenuated the mild stress-induced NE release in the BNST of EtOHW rats. Additionally, EtOHW rats showed increased solitary nNOS gene and protein expression. Moreover, the anxiolytic effect of intra-NTS administration of 7-NI was abolished by subsequent intra-NTS administration of sodium nitroprusside. These results suggest that elevation of solitary nitric oxide signaling derived from nNOS mediates stress-precipitated anxiety and norepinephrine release in the BNST during protracted EtOHW.