Brain Sci., Volume 12, Issue 10 (October 2022) – 156 articles

Purpose: Target temperature management (TTM) is often used in patients after cardiac arrest, but the effects of cooling on cerebral microcirculation, oxygenation and metabolism are poorly understood. We studied the time course of these variables in a healthy swine model.Methods: Fifteen invasively monitored, mechanically ventilated pigs were allocated to sham procedure (normothermia, NT; n = 5), cooling (hypothermia, HT, n = 5) or cooling with controlled oxygenation (HT-Oxy, n = 5). Cooling was induced by cold intravenous saline infusion, ice packs and nasal cooling to achieve a body temperature of 33–35 °C. After 6 h, animals were rewarmed to baseline temperature (within 5 h). The cerebral microvascular network was evaluated (at baseline and 2, 7 and 12 h thereafter) using sidestream dark-field (SDF) video-microscopy. Cerebral blood flow (laser Doppler MNP100XP, Oxyflow, Oxford Optronix, Oxford, UK), oxygenation (PbtO₂, Licox catheter, Integra Lifesciences, USA) and lactate/pyruvate ratio (LPR) using brain microdialysis (CMA, Stockholm, Sweden) were measured hourly. Results: In HT animals, cerebral functional capillary density (FCD) and proportion of small-perfused vessels (PSPV) significantly decreased over time during the cooling phase; concomitantly, PbtO₂ increased and LPR decreased. After rewarming, all microcirculatory variables returned to normal values, except LPR, which increased during the rewarming phase in the two groups subjected to HT when compared to the group maintained at normothermia. Conclusions: In healthy animals, TTM can be associated with alterations in cerebral microcirculation during cooling and altered metabolism at rewarming. Full article

Delayed diagnosis and a lack of adequate care for people with autism spectrum disorder (ASD) are related to worse outcomes and quality of life. This study aimed to identify the profile of service use, barriers to access care, and factors related to those barriers in Brazilian families with children with ASD. A total of 927 families with children with ASD (3–17 years) from five Brazilian regions completed an online version of the Caregivers Needs Survey. Results showed that the most used services were behavioral interventions and pharmacotherapy, while the most used professionals were neurologists, nutritionists, speech therapists, psychiatrists, psychologists, and pediatricians. The main barriers included waiting lists, costs, and the absence of services or treatment. Service use varied according to age, the region of residence, type of health care system used, and the parents/caregivers’ education. Access to behavioral interventions was more frequent among users of the private system/health insurance and families whose caregivers had higher education. The absence of specialized services/treatments was less frequent among residents of state capitals and families whose caregivers had higher levels of education. This study highlights how families with children/adolescents with ASD in Brazil face significant barriers to access care related to sociodemographic factors. Full article

Action observation (AO) combined with motor imagery (MI) was verified as more effective in improving limb function than AO or MI alone, while the underlying mechanism of swallowing was ambiguous. The study aimed at exploring the efficacy of AO combined with MI in swallowing. In this study, twelve subjects performed the motor imagery of swallowing (MI-SW) during magnetoencephalography (MEG) scanning, and trials were divided into three groups: the non-induced group (control group, CG), male AO-induced group (M-AIG), and female AO-induced group (F-AIG). We used event-related spectral perturbations (ERSPs) and phase locking value (PLV) to assess the degree of activation and connectivity of the brain regions during MI-SW in the three groups. The results showed that compared to CG, F-AIG and M-AIG significantly activated more brain regions in the frontoparietal, attention, visual, and cinguloopercular systems. In addition, M-AIG significantly activated the sensorimotor cortex compared to CG and F-AIG. For the brain network, F-AIG and M-AIG increased the diffusion of non-hub hot spots and cold hubs to the bilateral hemispheres which enhanced interhemispheric functional connectivity and information transmission efficiency in the MI-SW task. This study provided supporting evidence that AO induction could enhance the effect of MI-SW and supported the application of AO-induced MI-SW in clinical rehabilitation. Full article

Background: The recent introduction of near-infrared spectroscopy has enabled the monitoring of cerebral blood flow in real-time. Previous studies have shown that blood flow velocity is a predictor of cardiovascular disease. We hypothesized that cerebral oxygenation with a change in posture is a predictor for cerebral infarction. We designed a cross-sectional study to investigate the relationship between postural-related changes in cerebral oxygenation and a history of chronic cerebral infarction. Methods: A total of 100 consecutive participants were enrolled in this study. We evaluated changes in cerebral oxygenation with a change in posture from the supine to the upright position in the bilateral forehead. The association between a decline in cerebral oxygenation and chronic cerebral infarction was analyzed with multiple logistic regression adjusted for covariates. Results: Cerebral blood oxygenation increased in 52 participants and decreased in 48 participants with a postural change. The prevalence of decreased cerebral oxygenation was 76.3% in participants with chronic cerebral infarction. Multiple logistic regression analysis showed that a decline in cerebral oxygenation upon a postural change was strongly associated with chronic cerebral infarction (adjusted odds ratio: 3.42, p = 0.025). Conclusions: Cerebral blood oxygenation upon a postural change could be a useful predictor for cerebral infarction. Full article

Sound-induced flash illusion (SiFI) is typical auditory dominance phenomenon in multisensory illusion. Although a number of studies have explored the SiFI in terms of age-related effects, the reasons for the enhanced SiFI in older adults are still controversial. In the present study, older and younger adults with equal visual discrimination were selected to explore age differences in SiFI effects, and to explore the neural indicators by resting-state functional magnetic resonance imaging (rs-fMRI) signals. A correlation analysis was calculated to examine the relationship between regional homogeneity (ReHo) and the SiFI. The results showed that both younger and older adults experienced significant fission and fusion illusions, and fission illusions of older adults were greater than that of younger adults. In addition, our results showed ReHo values of the left middle frontal gyrus (MFG), the right inferior frontal gyrus (IFG) and right superior frontal gyrus (SFG) were significantly positively correlated with the SiFI in older adults. More importantly, the comparison between older and younger adults showed that ReHo values of the right superior temporal gyrus (STG) decreased in older adults, and this was independent of the SiFI. The results indicated that when there was no difference in unisensory ability, the enhancement of multisensory illusion in older adults may not always be explained by compensation mechanisms. Full article

The menstrual cycle affects women’s emotional states, with estrogen and progesterone having predominant roles. However, it remains unclear whether the phases of the menstrual cycle also affect women’s motivational behaviors. In this study, the main aim was to investigate how the menstrual cycle influences approach–avoidance behavior under conditions of conscious versus unconscious processing of emotions. Briefly, after recruitment by advertisement and screening with a menstrual cycle survey questionnaire, 27 naturally cycling, healthy women participated in an improved “manikin task” and were presented both positive and negative emotional stimuli during early follicular, late follicular, and mid-luteal phases. Estrogen and progesterone levels were measured. Women in the late follicular phase exhibited the shortest response times for approaching positive stimuli, while women in the mid-luteal phase exhibited the shortest response times for avoiding negative stimuli. Estrogen and progesterone levels significantly correlated with the speed of the approach–avoidance responses observed for the women, indicating the important role that sex hormones have in mediating emotionally motivated behavior. Overall, these findings suggest that the menstrual cycle has strong and specific influences on women’s approach–avoidance behaviors that are in part mediated by estrogen and progesterone. By identifying characteristics of these behaviors in the late follicular and mid-luteal phases, greater insight can be provided to women regarding the physiological influences of the menstrual cycle on their personal growth and security. Full article

The principal reason for measuring mental workload is to quantify the cognitive cost of performing tasks to predict human performance. Unfortunately, a method for assessing mental workload that has general applicability does not exist yet. This is due to the abundance of intuitions and several operational definitions from various fields that disagree about the sources or workload, its attributes, the mechanisms to aggregate these into a general model and their impact on human performance. This research built upon these issues and presents a novel method for mental workload modelling from EEG data employing deep learning. This method is self-supervised, employing a continuous brain rate, an index of cognitive activation, and does not require human declarative knowledge. The aim is to induce models automatically from data, supporting replicability, generalisability and applicability across fields and contexts. This specific method is a convolutional recurrent neural network trainable with spatially preserving spectral topographic head-maps from EEG data, aimed at fitting a novel brain rate variable. Findings demonstrate the capacity of the convolutional layers to learn meaningful high-level representations from EEG data since within-subject models had, on average, a test Mean Absolute Percentage Error of around 11%. The addition of a Long-Short Term Memory layer for handling sequences of high-level representations was not significant, although it did improve their accuracy. These findings point to the existence of quasi-stable blocks of automatically learnt high-level representations of cognitive activation because they can be induced through convolution and seem not to be dependent on each other over time, intuitively matching the non-stationary nature of brain responses. Additionally, across-subject models, induced with data from an increasing number of participants, thus trained with data containing more variability, obtained a similar accuracy to the within-subject models. This highlights the potential generalisability of the induced high-level representations across people, suggesting the existence of subject-independent cognitive activation patterns. This research contributes to the body of knowledge by providing scholars with a novel computational method for mental workload modelling that aims to be generally applicable and does not rely on ad hoc human crafted models. Full article

Purpose: The effect of scinderin (SCIN) on cancer progression has been studied, but its role in glioma remains unknown. This study describes the value of SCIN for the diagnosis, prognosis, and treatment of glioma. Methods: The expression of SCIN was analyzed using the GEPIA, Oncomine, cBioPortal, and CGGA databases. GO/KEGG enrichment analysis of similar genes to SCIN were performed using the R software package, and the protein–protein interaction (PPI) network was analyzed by the STRING and GeneMANIA databases. The correlations of mRNA expression between SCIN and MMP2/9 were analyzed by TCGA glioma. Simultaneously, the TISIDB and TIMER databases were used to analyze the correlation between SCIN and immune infiltration. Finally, SCIN and MMP2/9 protein expression among different grades of glioma was performed and the results were obtained via immunohistochemistry and Western blot assays. We used the Kaplan–Meier method and Cox proportional hazards model to assess the impact of SCIN and MMP2/9 on glioma patients’ survival. The correlations between SCIN and MMP2/9 were analyzed by immunohistochemistry and Western blot assays. Results: SCIN was upregulated in glioma patients with a poor prognosis. The GO and KEGG enrichment analysis showed the functional relationship between SCIN and the immune cell activation and regulation. In addition, the expression of SCIN was related to MMP2/9 in glioma. The correlation analysis showed that SCIN expression was associated with tumor purity and immune infiltration. SCIN and MMP2/9 are negative prognostic factors resulting in worsening glioma patients’ survival. Conclusion: Our studies demonstrated that SCIN expression was associated with MMP2/9, immune infiltration, and a poor prognosis in glioma. SCIN may serve as a potential prognostic marker and an immune therapy target for glioma. Full article

Several studies have revealed defects in autophagy in neurodegenerative disorders including Alzheimer’s disease (AD) and frontotemporal dementia (FTD). SQSTM1/p62 plays a key role in the autophagic machinery and may serve as a marker for autophagic flux in vivo. We investigated the role of p62 in neurodegeneration, analyzing its concentrations in the CSF of AD and FTD patients. We recruited 76 participants: 22 patients with AD, 28 patients with FTD, and 26 controls. CSF p62 concentrations were significantly increased in AD and FTD patients when compared to controls, which persisted after adjusting for age (p = 0.01 and p = 0.008, respectively). In female FTD patients, p62 positively correlated with the neurodegenerative biomarkers t-Tau and p-Tau. A significant correlation between CSF p62 concentrations and several clinical features of AD was found. Our data show that p62 is increased in CSF of AD and FTD patients, suggesting a key role of autophagy in these two disorders. The levels of p62 in CSF may reflect an altered autophagic flux, and p62 could represent a potential biomarker of neurodegeneration. Full article

Multi-site resting-state functional magnetic resonance imaging (rs-fMRI) data can facilitate learning-based approaches to train reliable models on more data. However, significant data heterogeneity between imaging sites, caused by different scanners or protocols, can negatively impact the generalization ability of learned models. In addition, previous studies have shown that graph convolution neural networks (GCNs) are effective in mining fMRI biomarkers. However, they generally ignore the potentially different contributions of brain regions- of-interest (ROIs) to automated disease diagnosis/prognosis. In this work, we propose a multi-site rs-fMRI adaptation framework with attention GCN (A²GCN) for brain disorder identification. Specifically, the proposed A²GCN consists of three major components: (1) a node representation learning module based on GCN to extract rs-fMRI features from functional connectivity networks, (2) a node attention mechanism module to capture the contributions of ROIs, and (3) a domain adaptation module to alleviate the differences in data distribution between sites through the constraint of mean absolute error and covariance. The A²GCN not only reduces data heterogeneity across sites, but also improves the interpretability of the learning algorithm by exploring important ROIs. Experimental results on the public ABIDE database demonstrate that our method achieves remarkable performance in fMRI-based recognition of autism spectrum disorders. Full article

Amyotrophic lateral sclerosis (ALS) is a fatal neuromuscular disease, characterized by the progressive degeneration of the upper and lower motor neurons in the cortex and spinal cord. Although the pathogenesis of ALS remains unclear, evidence concerning the role of the clonotypic immune system is growing. Adaptive immunity cells often appear changed in number, or in terms of their activation profiles, both peripherally and centrally; however, their role in ALS appears conflictive. Data from human and animal model studies, which are currently reported in the literature, show that each subset of lymphocytes and their mediators may mediate a protective or toxic mechanism in ALS, affecting both its progression and risk of death. In the present review, an attempt is made to shed light on the actual role of cellular clonotypic immunity in ALS by integrating recent clinical studies and experimental observations. Full article

Our ability to perform voluntary actions and make choices is shaped by the motivation from having control over the resulting effects (agency) and positive outcomes (reward). We offer an overview of distinct and common behavioral and neural signatures of agency and reward. We discuss their typical and atypical developmental trajectories, focusing on autism spectrum disorder (ASD), which is characterized by neurodiverse processes underlying action selection. We propose that reduced sensitivity to agency and reward in ASD may be related to atypical multisensory processes and motor planning, with potential for understanding restricted and repetitive behaviors. We emphasize the limitations of the existing literature, and prospects for future research. Understanding the neurocognitive processes that shape the way people with ASD select actions and perceive outcomes is essential to support not only learning, but also volition and self-determination. Full article

Female-specific risk factors for stroke have gradually received attention. The relationship between ischemic stroke and adenomyosis, a benign uterine disorder commonly present in parous women, is underrecognized. We aimed to provide an overview of the epidemiology, pathophysiological mechanisms, clinical characteristics, diagnostic considerations, and potential therapeutic strategies of adenomyosis-associated ischemic stroke. We shared our experience with the diagnosis and management of a patient, and summarized current findings and knowledge gaps of this disease based on previous literature. The relevant studies were searched in English and Chinese databases up to April 2022 using the keywords “ischemic stroke”, “cerebral infarction” and “adenomyosis”. Then, we provided a narrative review of the retrieved articles. Finally, the data of 32 cases were analyzed. We found that increased levels of carbohydrate antigen 125 and D-dimer and decreased level of hemoglobin are biomarkers of adenomyosis-associated ischemic stroke. In addition, hypercoagulability might be a key mechanism leading to thromboembolism in the cerebrovascular system. Additional studies are needed to find optimal prevention strategies for the disease. A better understanding of this “rare” pathogenesis of ischemic stroke may inform a more precise diagnosis and effective prevention strategy in middle-aged women with embolic stroke of undetermined source. Full article

This study pursued two goals: (1) to establish range of motion (ROM) demand tiers (i.e., low, moderate, high) specific to the jaw (J), lower lip (LL), posterior tongue (PT), and anterior tongue (AT) for multisyllabic words based on the articulatory performance of neurotypical talkers and (2) to identify demand- and disease-specific articulatory performance characteristics in talkers with amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD). J, LL, PT, and AT movements of 12 talkers with ALS, 12 talkers with PD, and 12 controls were recorded using electromagnetic articulography. Vertical ROM, average speed, and movement duration were measured. Results showed that in talkers with PD, J and LL ROM were already significantly reduced at the lowest tier whereas PT and AT ROM were only significantly reduced at moderate and high tiers. In talkers with ALS, J ROM was significantly reduced at the moderate tier whereas LL, PT, and AT ROM were only significantly reduced at the highest tier. In both clinical groups, significantly reduced J and LL speeds could already be observed at the lowest tier whereas significantly reduced AT speeds could only be observed at the highest tier. PT speeds were already significantly reduced at the lowest tier in the ALS group but not until the moderate tier in the PD group. Finally, movement duration, but not ROM or speed performance, differentiated between ALS and PD even at the lowest tier. Results suggest that articulatory deficits vary with stimuli-specific motor demands across articulators and clinical groups. Full article

Olfactory hedonic evaluation is the primary dimension of olfactory perception and thus central to our sense of smell. It involves complex interactions between brain regions associated with sensory, affective and reward processing. Despite a recent increase in interest, several aspects of olfactory hedonic evaluation remain ambiguous: uncertainty surrounds the communication between, and interaction among, brain areas during hedonic evaluation of olfactory stimuli with different levels of pleasantness, as well as the corresponding supporting oscillatory mechanisms. In our study we investigated changes in functional interactions among brain areas in response to odor stimuli using electroencephalography (EEG). To this goal, functional connectivity networks were estimated based on phase synchronization between EEG signals using the weighted phase lag index (wPLI). Graph theoretic metrics were subsequently used to quantify the resulting changes in functional connectivity of relevant brain regions involved in olfactory hedonic evaluation. Our results indicate that odor stimuli of different hedonic values evoke significantly different interaction patterns among brain regions within the olfactory cortex, as well as in the anterior cingulate and orbitofrontal cortices. Furthermore, significant hemispheric laterality effects have been observed in the prefrontal and anterior cingulate cortices, specifically in the beta ((13–30) Hz) and gamma ((30–40) Hz) frequency bands. Full article

Behavioural Activation (BA) is associated with a substantial evidence base for treatment of acute unipolar depression, and has promise as an easily disseminable psychological intervention for bipolar depression. Using a randomised multiple baseline case series design we examined the feasibility and acceptability of an adapted version of BA in a U.K. outpatient sample of 12 adults with acute bipolar depression. Participants were allocated at random to a 3–8 week wait period before being offered up to 20 sessions of BA. They completed outcome measures at intake, pre- and post-treatment and weekly symptom measures across the study period. Retention in therapy was high (11/12 participants completed the target minimum number of sessions), and all participants returning acceptability measures reported high levels of satisfaction with the intervention. No therapy-related serious adverse events were reported, nor were there exacerbations in manic symptoms that were judged to be a result of the intervention. The pattern of change on outcome measures is consistent with the potential for clinical benefit; six of the nine participants with a stable baseline showed clinically significant improvement on the primary outcome measure. The findings suggest adapted BA for bipolar depression is a feasible and acceptable approach that merits further investigation. Full article

Introduction: The approval process for MRI safety of implants includes physical observations and an experimental evaluation in artificial settings to simulate the in vivo effect. This contains the observation of temperature changes and artificial current generation by the magnetic field. From these findings, the safety of an implant and its effect on the patient can be estimated. MRI safety is based on an in vivo evaluation of adverse events after the approval process, but an actual analysis of the effect on different tissues is not followed. The effect of MRI scanning in cochlea implantees on their residual hearing as the correlate of the hair cell function is so far unknown, therefore the aim of the present study was to observe the effect of 3 T MRI on the residual hearing of cochlea implantees. Material and Methods: In this prospective study, we performed a 3 T MRI T2 2D MS Drive sequence in eight cochlea-implanted ears. Before and after the MRI scan, a bone conduction pure tone audiogram (BC PTA) was performed. All cochlea implantees had a pre-scanning threshold of low frequency residual hearing between 20 dB and 65 dB. Results: Low frequency mean residual hearing was not affected by the 3 T T2 2D MS Drive sequence. We observed a pre-scanning threshold at 250 Hz of 42.9 (SD 3.9) dB and for 500 Hz 57.1 (SD 6.4) dB. Post-scanning BC PTA was for 250 Hz 42.1 (SD 3.9) dB and for 500 Hz 57.1 (SD 5.7) dB. Conclusion: 3 T MRI scanning has no significant functional effect on the hair cells in cochlea implantees in low frequencies with a T2 2D MS Drive sequence. Full article

The COVID-19 pandemic has proven to be a challenge for healthcare systems, especially in terms of the care of patients with Alzheimer’s disease (AD). Age is one of the major risk factors for severe forms of COVID-19, most probably due to the presence of comorbidities and inflammations. It is known that SARS-CoV-2 invades nerve endings and olfactory nerves through the binding of the spike protein to the angiotensin-converting enzyme 2 (ACE2) receptor. This interaction triggers an inflammatory cascade that results in cognitive impairment. In turn, the isoform of apolipoprotein-E4 (APOE-4ε) in AD is a risk factor for increased neuroinflammation through microglia activation, increased oxidative stress, and neurodegeneration. AD and SARS-CoV-2 are associated with increases in levels of inflammatory markers, as well as increases in levels of APOE-4ε, ACE2 and oxidative stress. Thus, there is a synergistic relationship between AD and SARS-CoV-2. In addition, the social isolation and other health measures resulting from the pandemic have led to a higher level of anxiety and depression among AD patients, a situation which may lead to a decline in cognitive function. Therefore, there is a need to develop strategies for keeping the patient calm but active. Full article

Source activity was extracted from resting-state magnetoencephalography data of 103 subjects aged 18–60 years. The directionality of information flow was computed from the regional time courses using delay symbolic transfer entropy and phase entropy. The analysis yielded a dynamic source connectivity profile, disentangling the direction, strength, and time delay of the underlying causal interactions, producing independent time delays for cross-frequency amplitude-to-amplitude and phase-to-phase coupling. The computation of the dominant intrinsic coupling mode (DoCM) allowed me to estimate the probability distribution of the DoCM independently of phase and amplitude. The results support earlier observations of a posterior-to-anterior information flow for phase dynamics in {α₁, α₂, β, γ} and an opposite flow (anterior to posterior) in θ. Amplitude dynamics reveal posterior-to-anterior information flow in {α₁, α₂, γ}, a sensory-motor β-oriented pattern, and an anterior-to-posterior pattern in {δ, θ}. The DoCM between intra- and cross-frequency couplings (CFC) are reported here for the first time and independently for amplitude and phase; in both domains {δ, θ, α₁}, frequencies are the main contributors to DoCM. Finally, a novel brain age index (BAI) is introduced, defined as the ratio of the probability distribution of inter- over intra-frequency couplings. This ratio shows a universal age trajectory: a rapid rise from the end of adolescence, reaching a peak in adulthood, and declining slowly thereafter. The universal pattern is seen in the BAI of each frequency studied and for both amplitude and phase domains. No such universal age dependence was previously reported. Full article

Since depression remains a major public health issue there is a constant need for new and more efficient therapeutic strategies based on the mechanisms involved in the aetiology of depression. Thus, the pathogenic link between depression and inflammation is considered to play a potential key role in the development of such therapies. This review summarizes the results of various pharmacological (non-steroidal anti-inflammatory drugs, aspirin, cyclooxygenase inhibitors, cytokine inhibitors, corticosteroids, statins, minocycline, N-acetyl cysteine, omega-3 fatty acids and probiotics) and non-pharmacological interventions (electroconvulsive therapy, physical exercise and psychological therapy) and outlines their efficacy and discusses potential challenges. Both conventional and non-conventional anti-inflammatory drugs showed promising results according to the specific group of patients. The pre-existing pro-inflammatory status was, in most cases, a predictor for clinical efficacy and, in some cases, a correlation between clinical improvement and changes in various biomarkers was found. Some of the non-pharmacological interventions (physical exercise and electroconvulsive therapy) have also showed beneficial effects for depressive patients with elevated inflammatory markers. Treatments with anti-inflammatory action may improve clinical outcomes in depression, at least for some categories of patients, thus opening the way for a future personalised approach to patients with unipolar depression regarding the inflammation-related mechanism. Full article

The main objective of this study was to demonstrate that computational fluid dynamics (CFD) modeling can be used to study the contribution of covert and overt vascular architecture to the risk for cerebrovascular disease in sickle cell disease (SCD) and to determine the mechanisms of response to therapy such as chronic red blood cell (cRBC) transfusions. We analyzed baseline (screening), pre-randomization and study exit magnetic resonance angiogram (MRA) images from 10 (5 each from the transfusion and observation arms) pediatric sickle SCD participants in the silent cerebral infarct transfusion (SIT) trial using CFD modeling. We reconstructed the intracranial portion of the internal carotid artery and branches and extracted the geometry using 3D Slicer. We cut specific portions of the large intracranial artery to include segments of the internal carotid, middle, anterior, and posterior cerebral arteries such that the vessel segment analyzed extended from the intracranial beginning of the internal carotid artery up to immediately after (~0.25 inches) the middle cerebral artery branching point. Cut models were imported into Ansys 2021R2/2022R1 and laminar and time-dependent flow simulation was performed. Change in time averaged mean velocity, wall shear stress, and vessel tortuosity were compared between the observation and cRBC arms. We did not observe a correlation between time averaged mean velocity (TAMV) and mean transcranial Doppler (TCD) velocity at study entry. There was also no difference in change in time average mean velocity, wall shear stress (WSS), and vessel tortuosity between the observation and cRBC transfusion arms. WSS and TAMV were abnormal for 2 (developed TIA) out of the 3 participants (one participant had silent cerebral infarctions) that developed neurovascular outcomes. CFD approaches allow for the evaluation of vascular topology and hemodynamics in SCD using MRA images. In this proof of principle study, we show that CFD could be a useful tool and we intend to carry out future studies with a larger sample to enable more robust conclusions. Full article

Variability in the response of individuals to various non-invasive brain stimulation protocols is a major problem that limits their potential for clinical applications. Baseline motor-evoked potential (MEP) amplitude is the key predictor of an individual’s response to transcranial magnetic stimulation protocols. However, the factors that predict MEP amplitude and its variability remain unclear. In this study, we aimed to identify the input–output curve (IOC) parameters that best predict MEP amplitude and its variability. We analysed IOC data from 75 subjects and built a general linear model (GLM) using the IOC parameters as regressors and MEP amplitude at 120% resting motor threshold (RMT) as the response variable. We bootstrapped the data to estimate variability of IOC parameters and included them in a GLM to identify the significant predictors of MEP amplitude variability. Peak slope, motor threshold, and maximum MEP amplitude of the IOC were significant predictors of MEP amplitude at 120% RMT and its variability was primarily driven by the variability of peak slope and maximum MEP amplitude. Recruitment gain and maximum corticospinal excitability are the key predictors of MEP amplitude and its variability. Inter-individual variability in motor output may be reduced by achieving a uniform IOC slope. Full article

Number–color synesthesia is a condition in which synesthetes perceive numbers with concurrent experience of specific, corresponding colors. It has been proposed that synesthetic association exists primarily between representations of Arabic digit graphemes and colors, and a secondary, semantic connection between numerosity and colors is built via repeated co-activation. However, this distinction between the graphemic and semantic pathways of synesthetic number–color connection has not been empirically tested. The current study aims to dissociate graphemic and semantic aspects of color activations in number–color synesthesia by comparing their time courses. We adopted a synesthetic priming paradigm with varied stimuli onset asynchronies (SOAs). A number (2–6, prime) was presented in one of three notations: digit, dice, or non-canonical dot pattern, and a color patch (target) appeared with an SOA of 0, 100, 300, 400, or 800 ms. Participants reported the color as quickly as possible. Using the congruency effect (i.e., shorter reaction time when target color matched the synesthetic color of number prime) as an index of synesthetic color activation level, we revealed that the effect from the graphemic pathway is quick and relatively persistent, while the effect from the semantic pathway unfolds at a later stage and is more transient. The dissociation between the graphemic and semantic pathways of synesthesia implies further functional distinction within “conceptual synesthesia”, which has been originally discussed as a unitary phenomenon. This distinction has been demonstrated by the differential time courses of synesthetic color activations, and suggested that a presumed, single type of synesthesia could involve multiple mechanisms. Full article

Mild cognitive impairment (MCI) is one of the important comorbidities of type 2 diabetes mellitus (T2DM). It is critical to find appropriate methods for early diagnosis and objective assessment of mild cognitive impairment patients with type 2 diabetes (T2DM-MCI). Our study aimed to investigate potential early alterations in phase lag index (PLI) and determine whether it can distinguish between T2DM-MCI and normal controls with T2DM (T2DM-NC). EEG was recorded in 30 T2DM-MCI patients and 30 T2DM-NC patients. The phase lag index was computed and used in a logistic regression model to discriminate between groups. The correlation between the phase lag index and Montreal Cognitive Assessment (MoCA) score was assessed. The α-band phase lag index was significantly decreased in the T2DM-MCI group compared with the T2DM-NC group and showed a moderate degree of classification accuracy. The MoCA score was positively correlated with the α-band phase lag index (r = 0.4812, moderate association, p = 0.015). This work shows that the functional connectivity analysis of EEG may offer an effective way to track the cortical dysfunction linked to the cognitive deterioration of T2DM patients, and the α-band phase lag index may have a role in guiding the diagnosis of T2DM-MCI. Full article

Emotion regulation in old age was found to be more efficient; seniors seem to focus less on the negative aspects of experiences. Here, we ask, do older individuals regulate their emotions more efficiently or are they numb to the physiological changes that modulate these emotions? Interoception, the perception of physical feelings, influences a person’s mood, emotions, and sense of well-being, and was hardly tested among older adults. We examined the awareness of physiological changes (physiological arousal—blood pressure and heart rate) of 47 older adults, compared to 18 young adults, and their subjective reports of emotional experiences while viewing emotional stimuli. Interoception was decreased in old age. Blood pressure medications had a partial role in this reduction. Moreover, interoception mediated emotional experience, such that low interoception led to lower experiences of changes in physiological arousal. These findings may account for the emotional changes in old age, suggesting a decline in sensitivity with age, which leads to a positive interpretation of information. Full article

Plaque rupture of the basilar artery is one of the leading causes of posterior circulation stroke. The present study aimed to investigate the role of fluid dynamics in the ruptured fibrous cap of basilar artery plaques. Patients with basilar artery plaques (50–99% stenosis) were screened. Integrity of the fibrous cap was assessed by high-resolution MRI. Computational fluid dynamics models were built based on MR angiography to obtain the wall shear stress and velocity. A total of 176 patients were included. High-resolution MRI identified 35 ruptured fibrous caps of basilar artery plaques. Ruptured fibrous cap was significantly associated with acute infarction (27/35 vs. 96/141, p < 0.05) in the territory of the basilar artery. Proximal wall shear stress of stenosis was positively related with the ruptured fibrous cap (OR 1.564; 95% CI, 1.101–2.222; p = 0.013). The threshold of wall shear stress for the ruptured fibrous cap of basilar artery plaques was 4.84 Pa (Area under ROC 0.732, p = 0.008, 95%CI 0.565–0.899). The present study demonstrated that increased proximal wall shear stress of stenosis was associated with ruptured fibrous caps of basilar artery plaques. Full article

Background: The safety of the new vaccines against SARS-CoV-2 have already been shown, although data on patients with polyneuropathy are still lacking. The aim of this study is to evaluate the adherence to SARS-CoV-2 vaccination, as well as the reactogenicity to those vaccines in patients affected by neuropathy. Methods: A multicentric and web-based cross-sectional survey was conducted among patients affected by neuropathy from part of South Italy. Results: Out of 285 responders, n = 268 were included in the final analysis and n = 258 of them (96.3%) were fully vaccinated. Adherence to vaccination was higher in patients with hereditary neuropathies compared to others, while it was lower in patients with anti-MAG neuropathy (all p < 0.05). The overall prevalence of adverse events (AEs) was 61.2% and its occurrence was not associated with neuropathy type. Being female and of younger age were factors associated with higher risk of AEs, while having an inflammatory neuropathy and steroids assumption were associated with a lower risk (all p < 0.05). Younger age, having had an AE, and COVID-19 before vaccination were factors associated with symptoms worsening after vaccination (all p < 0.05). (4) Conclusions: Patients with neuropathy showed a high level of adherence to COVID-19 vaccination. Safety of vaccines in patients with neuropathies was comparable to the general population and it was more favorable in those with inflammatory neuropathy. Full article

The brain is susceptible to perturbations of redox balance, affecting neurogenesis and increasing the risks of psychiatric disorders. Thioredoxin-interacting protein (TXNIP) is an endogenous inhibitor of the thioredoxin antioxidant system. Its deletion or inhibition suggests protection for a brain with ischemic stroke or Alzheimer’s disease. Combined with conditional knockout mice and schizophrenia samples, we aimed to investigate the function of TXNIP in healthy brain and psychiatric disorders, which are under-studied. We found TXNIP was remarkedly expressed in the prefrontal cortex (PFC) during healthy mice’s prenatal and early postnatal periods, whereas it rapidly decreased throughout adulthood. During early life, TXNIP was primarily distributed in inhibitory and excitatory neurons. Contrary to the protective effect, the embryonic deletion of TXNIP in GABAergic (gamma-aminobutyric acid-ergic) neurons enhanced oxidative stress in PV⁺ interneurons of aging mice. The deleterious impact was brain region-specific. We also investigated the relationship between TXNIP and schizophrenia. TXNIP was significantly increased in the PFC of schizophrenia-like mice after MK801 administration, followed by oxidative stress. First episode and drug naïve schizophrenia patients with a higher level of plasma TXNIP displayed severer psychiatric symptoms than patients with a low level. We indicated a bidirectional function of TXNIP in the brain, whose high expression in the early stage is protective for development but might be harmful in a later period, associated with mental disorders. Full article

Brain decoding is to predict the external stimulus information from the collected brain response activities, and visual information is one of the most important sources of external stimulus information. Decoding functional magnetic resonance imaging (fMRI) based on visual stimulation is helpful in understanding the working mechanism of the brain visual function regions. Traditional brain decoding algorithms cannot accurately extract stimuli features from fMRI. To address these shortcomings, this paper proposed a brain decoding algorithm based on a graph convolution network (GCN). Firstly, 11 regions of interest (ROI) were selected according to the human brain visual function regions, which can avoid the noise interference of the non-visual regions of the human brain; then, a deep three-dimensional convolution neural network was specially designed to extract the features of these 11 regions; next, the GCN was used to extract the functional correlation features between the different human brain visual regions. Furthermore, to avoid the problem of gradient disappearance when there were too many layers of graph convolutional neural network, the residual connections were adopted in our algorithm, which helped to integrate different levels of features in order to improve the accuracy of the proposed GCN. The proposed algorithm was tested on the public dataset, and the recognition accuracy reached 98.67%. Compared with the other state-of-the-art algorithms, the proposed algorithm performed the best. Full article

Electroconvulsive therapy (ECT) is an effective therapy for many psychiatric illnesses. However, intracranial occupying lesions are a relative contraindication to ECT. Arachnoid cysts are benign, congenital, and space-occupying lesions. Our study aimed to evaluate the efficacy and tolerability of ECT in psychiatric patients with arachnoid cysts. We retrospectively identified 62 psychiatric patients with arachnoid cysts; 43 of them underwent ECT and 19 did not. Their conditions were assessed by CGI-S and different scales depending on different diagnoses (PANSS for schizophrenia; HAMD for depression; YMRS for bipolar disorder). The side effect was assessed by TESS. Significant differences were shown in the reduced scores of the CGI-S between patients who underwent ECT and those who did not (p = 0.001), while, at the same time, there was no significant difference in their TESS score (p = 0.297). The current study found that ECT is an effective and tolerable therapy for psychiatric patients with arachnoid cysts. Full article