Brain Sciences

Motor imagery brain–computer interface (MI-based BCIs) have demonstrated great potential in various applications. However, to well generalize classifiers to new subjects, a time-consuming calibration process is necessary due to high inter-subject variabilities of EEG signals. This process is costly and tedious, hindering the further expansion of MI-based BCIs outside of the laboratory. To reduce the calibration time of MI-based BCIs, we propose a novel domain adaptation framework that adapts multiple source subjects’ labeled data to the unseen trials of target subjects. Firstly, we train one Subject Separation Network(SSN) for each of the source subjects in the dataset. Based on adversarial domain adaptation, a shared encoder is constructed to learn similar representations for both domains. Secondly, to model the factors that cause subject variabilities and eliminate the correlated noise existing in common feature space, private feature spaces orthogonal to the shared counterpart are learned for each subject. We use a shared decoder to validate that the model is actually learning from task-relevant neurophysiological information. At last, an ensemble classifier is built by the integration of the SSNs using the information extracted from each subject’s task-relevant characteristics. To quantify the efficacy of the framework, we analyze the accuracy–calibration cost trade-off in MI-based BCIs, and theoretically guarantee a generalization bound on the target error. Visualizations of the transformed features illustrate the effectiveness of domain adaptation. The experimental results on the BCI Competition IV-IIa dataset prove the effectiveness of the proposed framework compared with multiple classification methods. We infer from our results that users could learn to control MI-based BCIs without a heavy calibration process. Our study further shows how to design and train Neural Networks to decode task-related information from different subjects and highlights the potential of deep learning methods for inter-subject EEG decoding. Full article

Amyotrophic lateral sclerosis (ALS) and myopathy have been already described as part of a common genetic syndrome called multisystem proteinopathy. They may occur together or not, and can be associated with other clinical features such as frontotemporal dementia and Paget’s bone disease. In addition, primary skeletal muscle involvement has been also reported in inherited forms of lower motor neuron disease, in spinal–bulbar muscular atrophy and in spinal muscular atrophy. We aim to characterize three sporadic, spinal-onset ALS patients, one with a concurrent non-specific myopathy, and two with a previous diagnosis of myopathy before upper and lower motor neuron signs emerged. Perhaps our sporadic ALS cases associated with myopathy share a common, but still unknown, pathogenic background. These cases raise the paradigm of a possible interplay between skeletal muscle degeneration and motor neuron damage. Full article

Background: Parkinson’s disease (PD) represents one of the most frequently seen neurodegenerative disorders, while anxiety accounts for its non-motor symptom (NMS), and it has greatly affected the life quality of PD cases. Bilateral subthalamic nucleus deep brain stimulation (STN-DBS) can effectively treat PD. This study aimed to develop a clinical prediction model for the anxiety improvement rate achieved in PD patients receiving STN-DBS. Methods: The present work retrospectively enrolled 103 PD cases undergoing STN-DBS. Patients were followed up for 1 year after surgery to analyze the improvement in HAMA scores. Univariate and multivariate logistic regression were conducted to select factors affecting the Hamilton Anxiety Scale (HAMA) improvement. A nomogram was established to predict the likelihood of achieving anxiety improvement. Receiver operating characteristic (ROC) curve analysis, decision curve analysis (DCA), and calibration curve analysis were conducted to verify nomogram performance. Results: The mean improvement in HAMA score was 23.9% in 103 patients; among them, 68.9% had improved anxiety, 25.2% had worsened (Preop) anxiety, and 5.8% had no significant change in anxiety. Education years, UPDRS-III preoperative score, and HAMA preoperative score were independent risk factors for anxiety improvement. The nomogram-predicted values were consistent with real probabilities. Conclusions: Collectively, a nomogram is built in the present work for predicting anxiety improvement probability in PD patients 1 year after STN-DBS. The model is valuable for determining expected anxiety improvement in PD patients undergoing STN-DBS. Full article

Co-occurrence of beta amyloid (Aβ) and white matter hyperintensities (WMHs) increase the risk of dementia and both are considered biomarkers of preclinical dementia. Moderation and mediation modeling were used to define the interplay between global and regional Aβ and WMHs measures in relation to executive function (EF) and memory composite scores outcomes at baseline and after approximately 2 years across a sample of 714 clinically normal participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI 2). The moderation regression analysis showed additive effects of Aβ and WMHs over baseline memory and EF scores (p = 0.401 and 0.061, respectively) and synergistic effects over follow-up EF (p < 0.05). Through mediation analysis, the data presented demonstrate that WMHs effects, mediated by global and regional amyloid burden, are responsible for baseline cognitive performance deficits in memory and EF. These findings suggest that Aβ and WMHs contribute to baseline cognition independently while WMHs volumes exert effects on baseline cognitive performance directly and through influences on Aβ accumulation. Full article

Background: While type 2 diabetes (T2D) is a major risk for ischemic stroke, the associated vessel wall characteristics remain essentially unknown. This study aimed to clarify intracranial vascular changes on three-dimensional vessel wall imaging (3D-VWI) using fast spin echo by employing 7Tesla (7T) magnetic resonance imaging (MRI) in T2D patients without advanced atherosclerosis as compared to healthy controls. Methods: In 48 T2D patients and 35 healthy controls, the prevalence of cerebral small vessel diseases and intracranial plaques were evaluated by 3D-VWI with 7T MRI. Results: The prevalence rate of lacunar infarction was significantly higher in T2D than in controls (n = 8 in T2D vs. n = 0 in control, p = 0.011). The mean number of intracranial plaques in both anterior and posterior circulation of each subject was significantly larger in T2D than in controls (2.23 in T2D vs. 0.94 in control, p < 0.01). In T2D patients, gender was associated with the presence of intracranial plaques. Conclusion: This is the first study to demonstrate the high prevalence of intracranial plaque in T2D patients with neither confirmed atherosclerotic disease nor symptoms by performing intracranial 3D-VWI employing 7TMRI. Investigation of intracranial VWI with 7T MRI is expected to provide novel insights allowing early intensive risk management for prevention of ischemic stroke in T2D patients. Full article

Glioblastoma multiforme (GBM) represents the most common and aggressive central nervous system tumor associated with a poor prognosis. The aim of this study was to depict the role of intraoperative imaging techniques in GBM surgery and how they can ensure the maximal extent of resection (EOR) while preserving the functional outcome. The authors conducted a systematic review following PRISMA guidelines on the PubMed/Medline and Scopus databases. A total of 1747 articles were identified for screening. Studies focusing on GBM-affected patients, and evaluations of EOR and functional outcomes with the aid of advanced image-guided techniques were included. The resulting studies were assessed for methodological quality using the Risk of Bias in Systematic Review tool. Open Science Framework registration DOI 10.17605/OSF.IO/3FDP9. Eighteen studies were eligible for this systematic review. Among the selected studies, eight analyzed Sodium Fluorescein, three analyzed 5-aminolevulinic acid, two evaluated IoMRI imaging, two evaluated IoUS, and three evaluated multiple intraoperative imaging techniques. A total of 1312 patients were assessed. Gross Total Resection was achieved in the 78.6% of the cases. Follow-up time ranged from 1 to 52 months. All studies assessed the functional outcome based on the Karnofsky Performance Status scale, while one used the Neurologic Assessment in Neuro-Oncology score. In 77.7% of the cases, the functional outcome improved or was stable over the pre-operative assessment. Combining multiple intraoperative imaging techniques could provide better results in GBM surgery than a single technique. However, despite good surgical outcomes, patients often present a neurocognitive decline leading to a marked deterioration of the quality of life. Advanced intraoperative image-guided techniques can allow a better understanding of the anatomo-functional relationships between the tumor and the surrounding brain, thus maximizing the EOR while preserving functional outcomes. Full article

The impact of cognitive impairments on the health-related quality of life (HRQoL) in individuals with schizophrenia is unclear. The aim of this study was to examine the association between cognitive impairments and HRQoL in individuals with schizophrenia. A total of 609 individuals with schizophrenia were assessed on the Positive and Negative Syndrome Scale (PANSS) and a neurocognitive battery which comprised of the Wechsler Abbreviated Scale of Intelligence matrix reasoning, the Benton Judgment of Line Orientation Test, Continuous Performance Tests-Identical Pairs, and the Brief Assessment of Cognition in Schizophrenia. A cognitive factor g was derived from the neurocognitive battery. EuroQol five-dimensional (EQ-5D-5L) utility scores were derived from PANSS scores via a previously validated algorithm and used as a measure of HRQoL. Hierarchical multiple regression was conducted to examine the association between cognitive factor g and the EQ-5D-5L. Cognitive factor g (β = 0.189, t = 4.956, p < 0.001) was found to be significantly associated with EQ-5D-5L scores. Age (β = −0.258, t = −6.776, p < 0.001), sex (β = 0.081, t = 2.117, p = 0.035), and being employed (β = 0.091, t = 2.317, p = 0.021) were also significant predictors of EQ-5D-5L. Our results add to the extant literature on the burden cognitive impairments exact in individuals with schizophrenia. More research is needed to develop effective interventions for cognitive impairments in schizophrenia. Full article

Background and Purpose: Minor acute ischemic stroke (AIS) patients—defined by an NIHSS score < 6—presenting with proximal middle cerebral artery large vessel occlusions (MCA-LVO) is a subgroup for which treatment is still debated. Although these patients present with minor symptoms initially, studies have shown that several patients afflicted with MCA-LVO in this subgroup experience cognitive and functional decline. Although mechanical thrombectomy (MT) is the standard of care for patients with an NIHSS score of 6 or higher, treatment in the minor stroke subgroup is still being explored. The purpose of this preliminary study is to report our center’s experience in evaluating the potential benefit of mechanical thrombectomy (MT) in minor stroke patients when compared to medical management (MM). Methods: We performed a retrospective study with two comprehensive stroke centers within our hospital enterprise of consecutive patients presenting with minor AIS secondary to MCA-LVO (defined as M1 or proximal M2 segments of MCA). We subsequently evaluated patients who received MT versus those who received MM. Results: Between January 2017 and July 2021, we identified 46 AIS patients (11 treated with MT and 35 treated with MM) who presented with an NIHSS score < 6 secondary to MCA-LVO (47.8% 22/46 female, mean age 62.3 years, range 49–75 years). MT was associated with a significantly lower mRS at 90 days (median: 1.0 [IQR 0.0–2.0] versus 3.0 [IQR 1.0–4.0], p = <0.001), a favorable NIHSS shift (−4.0 [IQR −10.0–−2.0] versus 0.0 [IQR −2.0–1.0], p = 0.002), favorable NIHSS shift dichotomization (5/11, 45.5% versus 3/35, 8.6%, p = 0.003) and favorable mRS dichotomization (7/11, 63.6% versus 14/35, 40.0%, p = 0.024). Conclusions: In our center’s preliminary experience, for AIS patients presenting with an NIHSS score < 6 secondary to MCA-LVO, MT may be associated with improved clinical outcomes when compared to MM only. Full article

It is a very alarming situation for the globe because 55 million humans are estimated to be affected by Alzheimer’s disease (AD) worldwide, and still it is increasing at the rapid speed of 10 million cases per year worldwide. This is an urgent reminder for better research and treatment due to the unavailability of a permanent medication for neurodegenerative disorders like AD. The lack of drugs for neurodegenerative disorder treatment is due to the complexity of the structure of the brain, mainly due to blood–brain barrier, because blood–brain drug molecules must enter the brain compartment. There are several novel and conventional formulation approaches that can be employed for the transportation of drug molecules to the target site in the brain, such as oral, intravenous, gene delivery, surgically implanted intraventricular catheter, nasal and liposomal hydrogels, and repurposing old drugs. A drug’s lipophilicity influences metabolic activity in addition to membrane permeability because lipophilic substances have a higher affinity for metabolic enzymes. As a result, the higher a drug’s lipophilicity is, the higher its permeability and metabolic clearance. AD is currently incurable, and the medicines available merely cure the symptoms or slow the illness’s progression. In the next 20 years, the World Health Organization (WHO) predicts that neurodegenerative illnesses affecting motor function will become the second-leading cause of mortality. The current article provides a brief overview of recent advances in brain drug delivery for AD therapy. Full article

Food deprivation and binge eating represent significant public health concerns. Previous studies have implicated that hypothalamic opioids are affected following food deprivation. However, the role of each opioid peptide is not fully understood. Therefore, we investigated the role of endogenous beta-endorphin in food deprivation-mediated increases in food intake and binge eating. Male mice lacking beta-endorphin and their respective controls were subjected to 24h food deprivation and then were randomly assigned to receive a regular diet (RD) or a high-fat diet (HFD). After four to five weeks, animals were re-exposed to an HFD to assess if previous exposure to HFD would enhance binge-eating behavior. We report that food deprivation significantly increases food intake; however, beta-endorphin may not be involved in this process. In addition, our findings suggest that prior exposure to an HFD promotes binge-eating behavior in wildtype mice, and that these effects were modestly decreased in beta-endorphin knockout mice. Overall, our results support that beta-endorphin may play a modest role in mediating palatability-driven feeding, but not hunger-associated feeding. A better understanding of neural mechanisms involved in binge eating and deprivation-induced increases in food intake may inspire new prevention or treatment options to decrease the burden of eating disorders. Full article

Anomalies of attentional selection have been repeatedly described in individuals with schizophrenia spectrum disorders. However, a precise analysis of their ability to inhibit irrelevant visual information during attentional selection is not documented. Recent behavioral as well as neurophysiological and computational evidence showed that attentional search among different competing stimuli elicits an area of suppression in the immediate surrounding of the attentional focus. In the present study, the strength and spatial extension of this surround suppression were tested in individuals with schizophrenia and neurotypical controls. Participants were asked to report the orientation of a visual “pop-out” target, which appeared in different positions within a peripheral array of non-target stimuli. In half of the trials, after the target appeared, a probe circle circumscribed a non-target stimulus at various target-to-probe distances; in this case, participants were asked to report the probe orientation instead. Results suggest that, as compared to neurotypical controls, individuals with schizophrenia showed stronger and spatially more extended filtering of visual information in the areas surrounding their attentional focus. This increased filtering of visual information outside the focus of attention might potentially hamper their ability to integrate different elements into coherent percepts and influence higher order behavioral, affective, and cognitive domains. Full article

Phonemic processing skills are impaired both in children and adults with dyslexia. Since phoneme representation development is based on articulatory gestures, it is likely that these gestures influence oral reading-related skills as assessed through phonemic awareness tasks. In our study, fifty-two young dyslexic adults, with and without motor impairment, and fifty-nine skilled readers performed reading, phonemic awareness, and articulatory tasks. The two dyslexic groups exhibited slower articulatory rates than skilled readers and the comorbid dyslexic group presenting with an additional difficulty in respiratory control (reduced speech proportion and increased pause duration). Two versions of the phoneme awareness task (PAT) with pseudoword strings were administered: a classical version under time pressure and a delayed version in which access to phonemic representations and articulatory programs was facilitated. The two groups with dyslexia were outperformed by the control group in both versions. Although the two groups with dyslexia performed equally well on the classical PAT, the comorbid group performed significantly less efficiently on the delayed PAT, suggesting an additional contribution of articulatory impairment in the task for this group. Overall, our results suggest that impaired phoneme representations in dyslexia may be explained, at least partially, by articulatory deficits affecting access to them. Full article

The introduction of intracerebroventricular (ICV) enzyme replacement therapy (ERT) for treatment of neuronal ceroid lipofuscinosis type 2 (CLN2) disease has produced dramatic improvements in disease management. However, assessments of therapeutic effect for ICV ERT are limited to clinical observational measures, namely the CLN2 Clinical Rating Scale, a subjective measure of motor and language performance. There is a need for an objective biomarker to enable assessments of disease progression and response to treatment. To address this, we investigated whether the proportion of cells with abnormal storage inclusions on electron microscopic examination of peripheral blood buffy coats could act as a biomarker of disease activity in CLN2 disease. We conducted a prospective longitudinal analysis of six patients receiving ICV ERT. We demonstrated a substantial and continuing reduction in the proportion of abnormal cells over the course of treatment, whereas symptomatic scores revealed little or no change over time. Here, we proposed the use of the proportion of cells with abnormal storage as a biomarker of response to therapy in CLN2. In the future, as more tissue-specific biomarkers are developed, the buffy coats may form part of a panel of biomarkers in order to give a more holistic view of a complex disease. Full article

Despite proving its usefulness for over a century, the concept of developmental dyslexia (DD) is currently in severe disarray because of the recent introduction of the phonological theory of its causation. Since mastering the phonological principle is essential for all reading, failure to do so cannot be used to distinguish DD from the many other causes of such failure. To overcome this problem, many new psychological, signal detection, and neurological theories have been introduced recently. All these new theories converge on the idea that DD is fundamentally caused by impaired signalling of the timing of the visual and auditory cues that are essential for reading. These are provided by large ‘magnocellular’ neurones which respond rapidly to sensory transients. The evidence for this conclusion is overwhelming. Especially convincing are intervention studies that have shown that improving magnocellular function improves dyslexic children’s reading, together with cohort studies that have demonstrated that the magnocellular timing deficit is present in infants who later become dyslexic, long before they begin learning to read. The converse of the magnocellular deficit in dyslexics may be that they gain parvocellular abundance. This may often impart the exceptional ‘holistic’ talents that have been ascribed to them and that society needs to nurture. Full article

It is controversial whether sarcasm processing should go through literal meaning processing. There is also a lack of eye movement evidence for Chinese sarcasm processing. In this study, we used eye movement experiments to explore the processing differences between sarcastic and literal meaning in Chinese text and whether this was regulated by sentence complexity. We manipulated the variables of complexity and literality. We recorded 33 participants’ eye movements when they were reading Chinese text and the results were analyzed by a linear mixed model. We found that, in the early stage of processing, there was no difference between the processing time of the sarcastic meaning and the literal meaning of simple remarks, whereas for complex remarks, the time needed to process the sarcastic meaning was longer than that needed to process the literal meaning. In the later stage of processing, regardless of complexity, the processing time of the sarcastic meaning was longer than that of the literal meaning. These results suggest that sarcastic speech processing in Chinese is influenced by literal meaning, and the effect of literal meaning on sarcastic remarks is regulated by complexity. Sarcastic meaning was expressed differently in different stages of processing. These results support the hierarchical salience hypothesis of the serial modular model. Full article

While borderline personality disorder (BPD) symptomatology has been studied extensively in clinical populations, the mechanisms underlying its manifestation in nonclinical populations remain largely understudied. One aspect of BPD symptomatology in nonclinical populations that has not been well studied is cognitive mechanisms, especially in relation to executive functions. To explore the cognitive mechanisms underlying BPD symptomatology in nonclinical populations, we analysed a large-scale dataset of 233 young adults that were administered with nine executive function tasks and BPD symptomatology assessments. Our structural equation modelling did not find any significant relations between latent factors of executive functions and the severity of BPD symptomatology. Contrary to our hypothesis, our result suggests that deficits in executive functions were not a risk factor for BPD symptomatology in the nonclinical young adult sample. Full article

A growing body of evidence suggests immune involvement in the pathology of multiple system atrophy (MSA). Research on detailed peripheral immune indices, however, is relatively sparse, and is one of the intriguing aspects of MSA yet to be elucidated. A total of 26 MSA patients and 56 age-and sex-matched healthy controls (HC) were enrolled in the current case-control study to delineate the peripheral immune traits of MSA patients. The ratio of CD4⁺/CD8⁺ T cells, natural killer cells, CD28 expression on both CD4⁺ T cells and CD8⁺ T cells increased in MSA patients compared to HC, but CD8⁺ T cells and active marker (HLA-DR) expression on total T cells decreased (p < 0.05). This study sheds light on the dysregulation of cellular immunity in MSA, pointing to future mechanistic research. Full article

Telepractice is increasingly finding its way into the care of people with dementia. Web-based delivery of speech and language therapy (SLT) is feasible and has the potential to improve communication in people with dementia-related speech disorders. Although experts are discussing the strengths and weaknesses of telepractice, a precise analysis of the differences between analogue and digital communication for this heterogeneous group of patients is still missing. The three current single cases investigated verbal and nonverbal aspects of communication in a face-to-face (F2F) and digital setting through a qualitative research design. Using the scenario-test (ST) in person and via big blue button (BBB; video conferencing system), several decisive factors were detected, influencing the effectiveness of communication in a F2F compared to a digital setting. The most important results of the qualitative content analysis are described for each case individually. Additionally, the influence of person-related factors, such as age, diagnosis, presence of depression, and level of education, is presented. Perceptual, executive, and affective disorders, as well as aids of relatives, are considered separately. The results indicate that executive functions, affects, and perceptual deficits need to be taken into account if telepractice is to be applied. Age, education, and distinct forms of dementia might be decisive for successful telepractice as well. Full article

Introduction: Feedback-related negativity (FRN) is electrical brain activity related to the function of monitoring behavior and its outcome. FRN is generated by negative feedback input, such as punishment or monetary loss, and its potential is distributed maximally over the frontal-central part of the skull. Our previous study demonstrated that FRN latency was delayed and that the amplitude was increased in patients with mild Alzheimer’s disease (AD). As mild cognitive impairment (MCI) is considered to be a prodromal stage of AD, we speculated that FRN would also be altered in MCI, as in AD. The aim of this study is to examine whether MCI patients showed changes in FRN during a gambling task. Methods: Thirteen MCI patients and thirteen age-matched healthy elderly individuals participated in a simple gambling task and underwent neuro-psychological assessments. The participants were asked to choose one out of two options and randomly received positive or negative feedback to their response. An EEG was recorded during the task, and FRN was obtained by subtracting the positive feedback-related activity from the negative feedback-related activity. Results: The reaction time to probe stimuli was comparable in the two groups. The group comparisons revealed that the FRN amplitude was significantly larger for the MCI group than for the healthy elderly (F(1,24) = 6.4, _p² = 0.22, p = 0.019), but there was no group difference in the FRN latency. The FRN amplitude at the frontocentral electrode positively correlated with the mini-mental state examination score (Spearman’s rho_partial = 0.41, p = 0.043). The finding of increased FRN amplitude in MCI was consistent with the previous finding in AD. Conclusion: Our findings indicate that monitoring dysfunction might also be involved in the prodromal stage of dementia. Full article