Amyotrophic Lateral Sclerosis (ALS) is characterized by the progressive degeneration of upper or lower motor neurons, leading to muscle wasting and paralysis, resulting in respiratory failure and death. The precise ALS aetiology is poorly understood, mainly due to clinical and genetic heterogeneity. Thus, the identification of reliable biomarkers of disease could be helpful in clinical practice. In this study, we investigated whether the levels of brain-derived neurotrophic factor (BDNF) and its precursor Pro-BDNF in serum and cerebrospinal fluid (CSF) may reflect the pathological changes related to ALS. We found higher BDNF and lower Pro-BDNF levels in ALS sera compared to healthy controls. BDNF/Pro-BDNF ratio turned out to be accurate in distinguishing ALS patients from controls. Then, the correlations of these markers with several ALS clinical variables were evaluated. This analysis revealed three statistically significant associations: (1) Patients carrying the C9orf72 expansion significantly differed from non-carrier patients and showed serum BDNF levels comparable to control subjects; (2) BDNF levels in CSF were significantly higher in ALS patients with faster disease progression; (3) lower serum levels of Pro-BDNF were associated with a shorter survival. Therefore, we suggest that BDNF and Pro-BDNF, alone or in combination, might be used as ALS prognostic biomarkers. Full article

Traumatic brain injury (TBI) remains a critical public health challenge. Although studies have found several prognostic factors for TBI, a useful early predictive tool for mortality has yet to be developed in the triage of the emergency room. This study aimed to use machine learning algorithms of artificial intelligence (AI) to develop predictive models for TBI patients in the emergency room triage. We retrospectively enrolled 18,249 adult TBI patients in the electronic medical records of three hospitals of Chi Mei Medical Group from January 2010 to December 2019, and undertook the 12 potentially predictive feature variables for predicting mortality during hospitalization. Six machine learning algorithms including logistical regression (LR) random forest (RF), support vector machines (SVM), LightGBM, XGBoost, and multilayer perceptron (MLP) were used to build the predictive model. The results showed that all six predictive models had high AUC from 0.851 to 0.925. Among these models, the LR-based model was the best model for mortality risk prediction with the highest AUC of 0.925; thus, we integrated the best model into the existed hospital information system for assisting clinical decision-making. These results revealed that the LR-based model was the best model to predict the mortality risk in patients with TBI in the emergency room. Since the developed prediction system can easily obtain the 12 feature variables during the initial triage, it can provide quick and early mortality prediction to clinicians for guiding deciding further treatment as well as helping explain the patient’s condition to family members. Full article

In this study, we examined the early value of automated quantitative pupillary examination, using the Neurological Pupil index (NPi), to predict the long-term outcome of acute brain injured (ABI) patients. We performed a single-centre retrospective study (October 2016–March 2019) in ABI patients who underwent NPi measurement during the first 3 days following brain insult. We examined the performance of NPi—alone or in combination with other baseline demographic (age) and radiologic (CT midline shift) predictors—to prognosticate unfavourable 6-month outcome (Glasgow Outcome Scale 1–3). A total of 145 severely brain-injured subjects (65 traumatic brain injury, TBI; 80 non-TBI) were studied. At each time point tested, NPi <3 was highly predictive of unfavourable outcome, with highest specificity (100% (90–100)) at day 3 (sensitivity 24% (15–35), negative predictive value 36% (34–39)). The addition of NPi, from day 1 following ABI to age and cerebral CT scan, provided the best prognostic performance (AUROC curve 0.85 vs. 0.78 without NPi, p = 0.008; DeLong test) for 6-month neurological outcome prediction. NPi, assessed at the early post-injury phase, has a superior ability to predict unfavourable long-term neurological outcomes in severely brain-injured patients. The added prognostic value of NPi was most significant when complemented with baseline demographic and radiologic information. Full article

Salivary Aβ40, Aβ42, t-tau, and p-tau 181 are commonly employed in Alzheimer’s disease (AD) investigations. However, the collection method of these biomarkers can affect their levels. To assess the impact of saliva collection methods on biomarkers in this study, 15 healthy people were employed in the morning with six saliva collection methods. The chosen methods were then applied in 30 AD patients and 30 non-AD controls. The levels of salivary biomarkers were calculated by a specific enzyme-linked immunosorbent assay. The receiver operating characteristic was utilized to assess salivary biomarkers in AD patients. The results demonstrated that the highest levels of salivary Aβ40, Aβ42, t-tau, and p-tau were in different saliva collection methods. The correlations between different saliva biomarkers in the same collection method were different. Salivary Aβ40, Aβ42, t-tau, and p-tau had no significant association. Salivary Aβ42 was higher in AD than in non-AD controls. However, p-tau/t-tau and Aβ42/Aβ40 had some relevance. The area under the curve for four biomarkers combined in AD diagnosis was 92.11%. An alternate saliva collection method (e.g., USS in Aβ40, UPS in Aβ42, t-tau, SSS in p-tau 181) was demonstrated in this study. Moreover, combining numerous biomarkers improves AD diagnosis. Full article

A growing body of research documents the persistence of physical and neuropsychiatric symptoms following the resolution of acute COVID-19 infection. To the best of our knowledge, no published study has examined the interaction between insomnia and mental health. Accordingly, we proposed to examine new diagnoses of insomnia, and referrals to pulmonary and sleep medicine clinics for treatment of sleep disorders, in patients presenting to one post-acute COVID-19 recovery clinic. Additionally, we aimed to examine the relationship between poor sleep quality, depression, anxiety, and post-traumatic stress. Patients presented to the clinic on average 2 months following COVID-19 infection; 51.9% (n = 41) were hospitalized, 11.4% (n = 9) were in the intensive care unit, 2.5% (n = 2) were on a mechanical ventilator, and 38.0% (n = 30) were discharged on oxygen. The most commonly reported symptom was fatigue (88%, n = 70), with worse sleep following a COVID-19 infection reported in 50.6% (n = 40). The mean PSQI score was 9.7 (82.3%, n = 65 with poor sleep quality). The mean GAD-7 score was 8.3 (22.8%, n = 14 with severe depression). The mean PHQ-9 was 10.1 (17.8%, n = 18 with severe anxiety). The mean IES-6 was 2.1 (54.4%, n = 43 with post-traumatic stress). Poor sleep quality was significantly associated with increased severity of depression, anxiety, and post-traumatic stress. Future work should follow patients longitudinally to examine if sleep, fatigue, and mental health symptoms improve over time. Full article

Growing evidence suggests that humans and other animals assign value to a stimulus based not only on its inherent rewarding properties, but also on the costs of the action required to obtain it, such as the cost of time. Here, we examined whether such cost also occurs for mentally simulated actions. Healthy volunteers indicated their subjective value for snack foods while the time to imagine performing the action to obtain the different stimuli was manipulated. In each trial, the picture of one food item and a home position connected through a path were displayed on a computer screen. The path could be either large or thin. Participants first rated the stimulus, and then imagined moving the mouse cursor along the path from the starting position to the food location. They reported the onset and offset of the imagined movements with a button press. Two main results emerged. First, imagery times were significantly longer for the thin than the large path. Second, participants liked significantly less the snack foods associated with the thin path (i.e., with longer imagery time), possibly because the passage of time strictly associated with action imagery discounts the value of the reward. Importantly, such effects were absent in a control group of participants who performed an identical valuation task, except that no action imagery was required. Our findings hint at the idea that imagined actions, like real actions, carry a cost that affects deeply how people assign value to the stimuli in their environment. Full article

Bilingualism and socio-economic status (SES) differentially affect linguistic and cognitive development. However, less evidence has been collected regarding their impact on literacy trajectories. The present longitudinal study evaluated the literacy development of language minority bilingual children (LMBC) and monolingual peers with different SES. A group of LMBC with low-SES (n = 18) and monolingual peers with low (n = 18) or high (n = 14) SES were followed from 2nd to 5th grade through a set of tasks assessing decoding (words, nonwords, passage), reading, and listening comprehension, and spelling skills. The results showed that all groups achieved better performances over time in all measures, except listening comprehension. However, low-SES LMBC underperformed in spelling tasks compared to the monolingual groups. In reading comprehension, there was a time*group interaction that showed how low-SES LMBC reached similar performances of low-SES monolinguals in fifth grade, but both groups underperformed compared to the high SES monolingual group. The discussion is focused on the need for research and educational settings to consider the differential impact of bilingualism and SES. Bilingualism seems to be associated with a longer time in developing adequate spelling skills, whereas SES was the primary underpinning of the reading comprehension gap over time. Full article

Background: Glioblastoma (GBM) is the most common primary brain tumor. The extent of resection (EOR) has been claimed as one of the most important prognostic factors. Fluorescent dyes aid surgeons in detecting a tumor’s borders. 5-aminolevulinic acid (5-ALA) and sodium fluorescein (SF) are the most used. Only a few studies have directly compared these two fluorophores. Methods: A single center retrospective analysis of patients treated for GBM in the period between January 2018 and January 2021 was built to find any differences in terms of EOR, Karnofsky Performance Status (KPS), and overall survival (OS) on the use of 5-ALA, SF, or both. Results: Overall, 99 patients affected by isocitrate dehydrogenase (IDH) wild-type Glioblastoma were included. 5-ALA was administered to 40 patients, SF to 44, and both to 15. No statistically significant associations were identified between the fluorophore and EOR (p = 0.783) or postoperative KPS (p = 0.270). Survival analyses did not show a selective advantage for the use of a given fluorophore (p = 0.184), although there appears to be an advantageous trend associated with the concomitant use of both dyes, particularly after stratification by MGMT (p = 0.071). Conclusions: 5-Ala and SF are equally useful in achieving gross total resection of the enhancing tumor volume. The combination of both fluorophores could lead to an OS advantage. Full article

Diabetic retinopathy (DR) is a visual obstacle caused by diabetic disease, which forms because of long-standing diabetes mellitus, which damages the retinal blood vessels. This disease is considered one of the principal causes of sightlessness and accounts for more than 158 million cases all over the world. Since early detection and classification could diminish the visual impairment, it is significant to develop an automated DR diagnosis method. Although deep learning models provide automatic feature extraction and classification, training such models from scratch requires a larger annotated dataset. The availability of annotated training datasets is considered a core issue for implementing deep learning in the classification of medical images. The models based on transfer learning are widely adopted by the researchers to overcome annotated data insufficiency problems and computational overhead. In the proposed study, features are extracted from fundus images using the pre-trained network VGGNet and combined with the concept of transfer learning to improve classification performance. To deal with data insufficiency and unbalancing problems, we employed various data augmentation operations differently on each grade of DR. The results of the experiment indicate that the proposed framework (which is evaluated on the benchmark dataset) outperformed advanced methods in terms of accurateness. Our technique, in combination with handcrafted features, could be used to improve classification accuracy. Full article

Olfactory dysfunction (OD) is a common symptom in coronavirus disease 2019 (COVID-19) patients. Moreover, many neurological manifestations have been reported in these patients, suggesting central nervous system involvement. The default mode network (DMN) is closely associated with olfactory processing. In this study, we investigated the internetwork and intranetwork connectivity of the DMN and the olfactory network (ON) in 13 healthy controls and 22 patients presenting with COVID-19-related OD using independent component analysis and region of interest functional magnetic resonance imaging (fMRI) analysis. There was a significant correlation between the butanol threshold test (BTT) and the intranetwork connectivity in ON. Meanwhile, the COVID-19 patients with OD showed significantly higher intranetwork connectivity in the DMN, as well as higher internetwork connectivity between ON and DMN. However, no significant difference was found between groups in the intranetwork connectivity within ON. We postulate that higher intranetwork functional connectivities compensate for the deficits in olfactory processing and general well-being in COVID-19 patients. Nevertheless, the compensation process in the ON may not be obvious at this stage. Our results suggest that resting-state fMRI is a potentially valuable tool to evaluate neurosensory dysfunction in COVID-19 patients. Full article

Trait empathy is an essential personality feature in the intricacy of typical social inclinations of individuals. Empathy is likely supported by multilevel neuronal network functioning, whereas local topological properties determine network integrity. In the present functional MRI study (N = 116), we aimed to trace empathic traits to the intrinsic brain network architecture. Empathy was conceived as composed of two dimensions within the concept of pre-reflective, intersubjective understanding. Vicarious experience consists of the tendency to resonate with the feelings of other individuals, whereas intuitive understanding refers to a natural awareness of others’ emotional states. Analyses of graph theoretical measures of centrality showed a relationship between the fronto-parietal network and psychometric measures of vicarious experience, whereas intuitive understanding was associated with sensorimotor and subcortical networks. Salience network regions could constitute hubs for information processing underlying both dimensions. The network properties related to empathy dimensions mainly concern inter-network information flow. Moreover, interaction effects implied several sex differences in the relationship between functional network organization and trait empathy. These results reveal that distinct intrinsic topological network features explain individual differences in separate dimensions of intersubjective understanding. The findings could help understand the impact of brain damage or stimulation through alterations of empathy-related network integrity. Full article

Background: Oligoclonal bands represent intrathecal immunoglobulin G (IgG) synthesis and play an important role in the diagnosis of multiple sclerosis (MS). Kappa free light chains (KFLC) are increasingly recognized as an additional biomarker for intrathecal Ig synthesis. However, there are limited data on KFLC in neurological diseases other than MS. Methods: This study, conducted at two centers, retrospectively enrolled 346 non-MS patients. A total of 182 patients were diagnosed with non-inflammatory and 84 with inflammatory neurological diseases other than MS. A further 80 patients were classified as symptomatic controls. Intrathecal KFLC production was determined using different approaches: KFLC index, Reiber’s diagram, Presslauer’s exponential curve, and Senel’s linear curve. Results: Matching results of oligoclonal bands and KFLC (Reiber’s diagram) were frequently observed (93%). The Reiber’s diagram for KFLC detected intrathecal KFLC synthesis in an additional 7% of the patient samples investigated (4% non-inflammatory; 3% inflammatory), which was not found by oligoclonal band detection. Conclusions: The determination of both biomarkers (KFLC and oligoclonal bands) is recommended for routine diagnosis and differentiation of non-inflammatory and inflammatory neurological diseases. Due to the high sensitivity and physiological considerations, the assessment of KFLC in the Reiber’s diagram should be preferred to other evaluation methods. Full article

Transcranial direct-current stimulation (tDCS) over the prefrontal cortex can improve signs of consciousness in patients in a minimally conscious state. Transcranial pulsed-current stimulation (tPCS) over the mastoids can modulate brain activity and connectivity in healthy controls. This study investigated the feasibility of tPCS as a therapeutic tool in patients with disorders of consciousness (DoC) and compared its neurophysiological and behavioral effects with prefrontal tDCS. This pilot study was a randomized, double-blind sham-controlled clinical trial with three sessions: bi-mastoid tPCS, prefrontal tDCS, and sham. Electroencephalography (EEG) and behavioral assessments were collected before and after each stimulation session. Post minus pre differences were compared using Kruskal–Wallis and Wilcoxon signed-rank tests. Twelve patients with DoC were included in the study (eight females, four traumatic brain injury, 50.3 ± 14 y.o., 8.8 ± 10.5 months post-injury). We did not observe any side-effects following tPCS, nor tDCS, and confirmed their feasibility and safety. We did not find a significant effect of the stimulation on EEG nor behavioral outcomes for tPCS. However, consistent with prior findings, our exploratory analyses suggest that tDCS induces behavioral improvements and an increase in theta frontal functional connectivity. Full article

The promotion of recovery in patients who have entered a disorder of consciousness (DOC; e.g., coma or vegetative states) following severe brain injury remains an enduring medical challenge despite an ever-growing scientific understanding of these conditions. Indeed, recent work has consistently implicated altered cortical modulation by deep brain structures (e.g., the thalamus and the basal ganglia) following brain damage in the arising of, and recovery from, DOCs. The (re)emergence of low-intensity focused ultrasound (LIFU) neuromodulation may provide a means to selectively modulate the activity of deep brain structures noninvasively for the study and treatment of DOCs. This technique is unique in its combination of relatively high spatial precision and noninvasive implementation. Given the consistent implication of the thalamus in DOCs and prior results inducing behavioral recovery through invasive thalamic stimulation, here we applied ultrasound to the central thalamus in 11 acute DOC patients, measured behavioral responsiveness before and after sonication, and applied functional MRI during sonication. With respect to behavioral responsiveness, we observed significant recovery in the week following thalamic LIFU compared with baseline. With respect to functional imaging, we found decreased BOLD signals in the frontal cortex and basal ganglia during LIFU compared with baseline. In addition, we also found a relationship between altered connectivity of the sonicated thalamus and the degree of recovery observed post-LIFU. Full article

Neurocognitive deficits have been consistently associated with a wide range of psychopathology and are proposed to not only be a consequence of the development of psychopathology but also directly involved in its aetiology. However, there is no clear understanding of what neurocognitive processes are particularly important to mental health. In this paper, we explored the association between neurocognitive abilities and the factors derived from structural models of psychopathology. Four hundred participants from a representative community sample completed measures of symptomology and substance use, as well as 8 neurocognitive tasks. We found a correlated-factors model, with internalising and externalising as the higher-order factors, and a single-factor model with only the p-factor, to be good fits for the data. Tasks that measured the speed of processing were significantly associated with internalising, externalising, and the p-factor, and accounted for significant amounts of unique variance in the factors after accounting for the common variance of the other tasks. Tasks that measured working memory, shifting, and inhibition were not significantly associated with psychopathology factors. Our findings suggest that neurocognitive abilities may not be differentially associated with psychopathology factors, but that speed of processing is a common correlate of the factors. We emphasise the importance of examining neurocognitive abilities and psychopathology on the individual level. Full article

Music’s deeply interpersonal nature suggests that music-derived neuroplasticity relates to interpersonal temporal dynamics, or synchrony. Interpersonal neural synchrony (INS) has been found to correlate with increased behavioral synchrony during social interactions and may represent mechanisms that support them. As social interactions often do not have clearly delineated boundaries, and many start and stop intermittently, we hypothesize that a neural signature of INS may be detectable following an interaction. The present study aimed to investigate this hypothesis using a pre-post paradigm, measuring interbrain phase coherence before and after a cooperative dyadic musical interaction. Ten dyads underwent synchronous electroencephalographic (EEG) recording during silent, non-interactive periods before and after a musical interaction in the form of a cooperative tapping game. Significant post-interaction increases in delta band INS were found in the post-condition and were positively correlated with the duration of the preceding interaction. These findings suggest a mechanism by which social interaction may be efficiently continued after interruption and hold the potential for measuring neuroplastic adaption in longitudinal studies. These findings also support the idea that INS during social interaction represents active mechanisms for maintaining synchrony rather than mere parallel processing of stimuli and motor activity. Full article

Despite extensive research on COVID-19’s impact on healthcare workers, few studies have targeted mental health workers (MHWs) and none have investigated previous traumatic events. We investigated psychological distress in MHWs after the first lockdown in Italy to understand which COVID-19, sociodemographic, and professional variables represented greater effects, and the role of previous trauma. The survey included sociodemographic and professional questions, COVID-19 variables, and the questionnaires Life Events Checklist for DSM-5 (LEC-5), Impact of Event Scale—Revised (IES-R), and Depression Anxiety Stress Scales 21 (DASS-21). On the 271 MHWs who completed the survey (73.1% female; mean age 45.37), we obtained significant effects for contagion fear, experience of patients’ death, increased workload, and worse team relationship during the first wave. Nurses were more affected and showed more post-traumatic stress symptoms, assessed by IES-R, and more depressive, anxiety, and stress symptoms, assessed by DASS-21. The strongest risk factors for distress were greater age, professional role, increased workload, worse team relationship, and separation from family members. Previous experience of severe human suffering and unwanted sexual experiences negatively impacted IES-R and DASS-21 scores. Being a psychiatrist or psychologist/psychotherapist and good team relationships were protective factors. Recent but also previous severe stressful events might represent relevant risk factors for distress, reducing resilience skills. Identifying vulnerable factors and professional categories may help in the development of dedicated measures to prevent emotional burden and support psychological health. Highlights: Psychological distress in mental health workers in the COVID-19 pandemic is more frequent in nurses, who experience more depression, anxiety, and post-traumatic stress symptoms. Previous and recent stressful events are risk factors for distress and should guide intervention strategies. Full article

Background: Both depressive disorders (DD) and post-traumatic stress disorders (PTSD) are caused by immune system dysfunction. Affected individuals show increased proinflammatory cytokine concentration levels. Also, it has been hypothesized that DD and PTSD might be associated with a generalized proinflammatory cytokine signature. The study assessed the concentration of IL-1β, IL-4, IL-8 and IL-10 in depression alone and with PTSD. Methods: The study involved 460 participants. Out of them, 420 subjects comprised a study group and 40 subjects comprised a control group. Each study group consisted of 60 patients with mild depression (MD), moderate depression (MOD), severe depression (SeD), MD and PTSD (MD + PTSD), MOD and PTSD (MOD + PTSD), SeD and PTSD (SeD + PTSD), and with PTSD alone. All patients had serum concentration of IL-1β, IL-4, IL-8 and IL-10 measured with ELISA. Results: DD and PTSD are reflected in IL-1β, IL-4, IL-8 and IL-10 concentration levels. It was reported that mean levels of IL-1β, IL-4, IL-8 increase as depression became more severe. A regular decrease in IL-10 concentration levels was noted with the onset and exacerbation of depressive symptoms. Conclusion: The findings might be useful when considering chronic inflammation as a potential target or biomarker in depression and PTSD treatment. Full article

Epilepsy is a common brain disorder characterized by a heterogenous etiology. Its main features are recurrent seizures. Despite many clinical studies, about 30% of cases are refractory to treatment. Recent studies suggested the important role of immune-system elements in its pathogenesis. It was suggested that a deregulated inflammatory process may lead to aberrant neural connectivity and the hyperexcitability of the neuronal network. The aim of our study was the analysis of the expression of inflammatory mediators in a mouse model of epilepsy and their impact on the neurodegeneration process located in the brain. We used the KA-induced model of epilepsy in SJL/J mice and performed the analysis of gene expression and protein levels. We observed the upregulation of IL1β and CXCL12 in the early phase of KA-induced epilepsy and elevated levels of CCL5 at a later time point, compared with control animals. The most important result obtained in our study is the elevation of CXCL2 expression at both studied time points and its correlation with the neurodegeneration observed in mouse brain. Increasing experimental and clinical data suggest the influence of peripheral inflammation on epileptogenesis. Thus, studies focused on the molecular markers of neuroinflammation are of great value and may help deepen our knowledge about epilepsy, leading to the discovery of new drugs. Full article

Patients with Parkinson’s disease (PD) can improve some non-motor symptoms (NMS) after starting treatment with opicapone. The aim of this study was to analyze the effectiveness of opicapone on global NMS burden in PD. OPEN-PD (Opicapone Effectiveness on Non-motor symptoms in Parkinson’s Disease) is a prospective open-label single-arm study conducted in 5 centers from Spain. The primary efficacy outcome was the change from baseline (V0) to the end of the observational period (6 months ± 30 days) (V2) in the Non-Motor Symptoms Scale (NMSS) total score. Different scales were used for analyzing the change in motor, NMS, quality of life (QoL), and disability. Thirty-three patients were included between JUL/2019 and JUN/2021 (age 63.3 ± 7.91; 60.6% males; 7.48 ± 4.22 years from symptoms onset). At 6 months, 30 patients completed the follow-up (90.9%). The NMSS total score was reduced by 27.3% (from 71.67 ± 37.12 at V0 to 52.1 ± 34.76 at V2; Cohen’s effect size = −0.97; p = 0.002). By domains, improvement was observed in sleep/fatigue (−40.1%; p < 0.0001), mood/apathy (−46.6%; p = 0.001), gastrointestinal symptoms (−20.7%; p = 0.029), and miscellaneous (−44.94%; p = 0.021). QoL also improved with a 18.4% reduction in the 39-item Parkinson’s Disease Quality of Life Questionnaire Summary Index (from 26.67 ± 17.61 at V0 to 21.75 ± 14.9 at V2; p = 0.001). A total of 13 adverse events in 11 patients (33.3%) were reported, 1 of which was severe (not related to opicapone). Dyskinesias and nausea were the most frequent (6.1%). Opicapone is well tolerated and improves global NMS burden and QoL in PD patients at 6 months. Full article

Obsessive-compulsive disorder is a mental disorder characterized by repetitive, unwanted thoughts and behavior due to abnormal neuronal corticostriatal-thalamocortical pathway and other neurochemical changes. Purmorphamine is a smoothened-sonic-hedgehog agonist that has a protective effect against many neurological diseases due to its role in maintaining functional connectivity during CNS development and its anti-inflammatory and antioxidant properties. As part of our current research, we investigated the neuroprotective effects of PUR against behavioral and neurochemical changes in 8-hydroxy-2-(di-n-propylamino)-tetralin-induced obsessive-compulsive disorder in rats. Additionally, the effect of PUR was compared with the standard drug for OCD, i.e., fluvoxamine. The intra-dorsal raphe-nucleus injection of 8-OH-DPAT in rats for seven days significantly showed OCD-like repetitive and compulsive behavior along with increased oxidative stress, inflammation, apoptosis, as well as neurotransmitter imbalance. These alterations were dose-dependently attenuated by long-term purmorphamine treatment at 5 mg/kg and 10 mg/kg i.p. In this study, we assessed the level of various neurochemical parameters in different biological samples, including brain homogenate, blood plasma, and CSF, to check the drug’s effect centrally and peripherally. These effects were comparable to the standard oral treatment withfluvoxamine at 10 mg/kg. However, when fluvoxamine was given in combination with purmorphamine, there was a more significant restoration of these alterations than the individualtreatmentswithfluvoxamine and purmorphamine. All the above findings demonstrate that the neuroprotective effect of purmorphamine in OCD can be strong evidence for developing a new therapeutic target for treating and managing OCD. Full article

Positive and negative moods tend to have differential effects on lexico-semantic processing in the native language (L1). Though accumulating evidence points to dampened sensitivity to affective stimuli in the non-native language (L2), little is known about the effects of positive and negative moods on L2 processing. Here, we show that lexico-semantic processing is differently affected by positive and negative moods only in L1. Unbalanced Polish–English bilinguals made meaningfulness judgments on L1 and L2 sentences during two EEG recording sessions featuring either positive- or negative-mood-inducing films. We observed a reduced N1 (lexical processing) for negative compared to positive mood in L2 only, a reduced N2 (lexico-semantic processing) in negative compared to positive mood in L1 only, a reduced N400 (lexico-semantic processing) for meaningless compared to meaningful L1 sentences in positive mood only, and an enhanced late positive complex (semantic integration and re-analysis) for L2 compared to L1 meaningful sentence in negative mood only. Altogether, these results suggest that positive and negative moods affect lexical, lexico-semantic, and semantic processing differently in L1 and L2. Our observations are consistent with previous accounts of mood-dependent processing and emotion down-regulation observed in bilinguals. Full article

Therapeutic interventions are greatly needed for age-related neurodegenerative diseases. Astrocytes regulate many aspects of neuronal function including bioenergetics and synaptic transmission. Reactive astrocytes are implicated in neurodegenerative diseases due to their pro-inflammatory phenotype close association with damaged neurons. Thus, strategies to reduce astrocyte reactivity may support brain health. Caloric restriction and a ketogenic diet limit energy production via glycolysis and promote oxidative phosphorylation, which has gained traction as a strategy to improve brain health. However, it is unknown how caloric restriction affects astrocyte reactivity in the context of neuroinflammation. We investigated how a caloric restriction mimetic and glycolysis inhibitor, 2-deoxyglucose (2-DG), affects interleukin 1β-induced inflammatory gene expression in human astrocytes. Human astrocyte cultures were exposed to 2-DG or vehicle for 24 h and then to recombinant IL-1β for 6 or 24 h to analyze mRNA and protein expression, respectively. Gene expression levels of proinflammatory genes (complement component 3, IL-1β, IL6, and TNFα) were analyzed by real-time PCR, immunoblot, and immunohistochemistry. As expected, IL-1β induced elevated levels of proinflammatory genes. 2-DG reversed this effect at the mRNA and protein levels without inducing cytotoxicity. Collectively, these data suggest that inhibiting glycolysis in human astrocytes reduces IL-1β-induced reactivity. This finding may lead to novel therapeutic strategies to limit inflammation and enhance bioenergetics toward the goal of preventing and treating neurodegenerative diseases. Full article

Driver’s stress affects decision-making and the probability of risk occurrence, and it is therefore a key factor in road safety. This suggests the need for continuous stress monitoring. This work aims at validating a stress neurophysiological measure—a Neurometric—for out-of-the-lab use obtained from lightweight EEG relying on two wet sensors, in real-time, and without calibration. The Neurometric was tested during a multitasking experiment and validated with a realistic driving simulator. Twenty subjects participated in the experiment, and the resulting stress Neurometric was compared with the Random Forest (RF) model, calibrated by using EEG features and both intra-subject and cross-task approaches. The Neurometric was also compared with a measure based on skin conductance level (SCL), representing one of the physiological parameters investigated in the literature mostly correlated with stress variations. We found that during both multitasking and realistic driving experiments, the Neurometric was able to discriminate between low and high levels of stress with an average Area Under Curve (AUC) value higher than 0.9. Furthermore, the stress Neurometric showed higher AUC and stability than both the SCL measure and the RF calibrated with a cross-task approach. In conclusion, the Neurometric proposed in this work proved to be suitable for out-of-the-lab monitoring of stress levels. Full article

Currently, there is little understanding of how interoceptive attentiveness (IA) affects brain responses during synchronized cognitive or motor tasks. This pilot study explored the effect of explicit IA manipulation on hemodynamic correlates of simple cognitive tasks implying linguistic or motor synchronization. Eighteen healthy participants completed two linguistic and motor synchronization tasks during explicit IA and control conditions while oxygenated (O2Hb) and deoxygenated (HHb) hemoglobin variations were recorded by functional Near-Infrared Spectroscopy (fNIRS). The findings suggested that the brain regions associated with sustained attention, such as the right prefrontal cortex (PFC), were more involved when an explicit focus on the breath was induced during the cognitive linguistic task requiring synchronization with a partner, as indicated by increased O2Hb. Interestingly, this effect was not significant for the motor task. In conclusion, for the first time, this pilot research found increased activity in neuroanatomical regions that promote sustained attention, attention reorientation, and synchronization when a joint task is carried out and the person is focusing on their physiological body reactions. Moreover, the results suggested that the benefits of conscious concentration on physiological interoceptive correlates while executing a task demanding synchronization, particularly verbal alignment, may be related to the right PFC. Full article

Objectives: (1) To determine which psychosocial aspects predict tinnitus-related distress in a large self-reported dataset of patients with chronic tinnitus, and (2) to identify underlying constructs by means of factor analysis. Methods: A cohort of 1958 patients of the Charité Tinnitus Center, Berlin completed a large questionnaire battery that comprised sociodemographic data, tinnitus-related distress, general psychological stress experience, emotional symptoms, and somatic complaints. To identify a construct of “tinnitus-related distress”, significant predictive items were grouped using factor analysis. Results: For the prediction of tinnitus-related distress (linear regression model with R² = 0.7), depressive fatigue symptoms (concentration, sleep, rumination, joy decreased), the experience of emotional strain, somatization tendencies (pain experience, doctor contacts), and age appeared to play a role. The factor analysis revealed five factors: “stress”, “pain experience”, “fatigue”, “autonomy”, and low “educational level”. Conclusions: Tinnitus-related distress is predicted by psychological and sociodemographic indices. Relevant factors seem to be depressive exhaustion with somatic expressions such as sleep and concentration problems, somatization, general psychological stress, and reduced activity, in addition to higher age. Full article

Dementia is a neurodegenerative disease that leads to the development of cognitive deficits, such as aphasia, apraxia, and agnosia. It is currently considered one of the most significant major medical problems worldwide, primarily affecting the elderly. This condition gradually impairs the patient’s cognition, eventually leading to the inability to perform everyday tasks without assistance. Since dementia is an incurable disease, early detection plays an important role in delaying its progression. Because of this, tools and methods have been developed to help accurately diagnose patients in their early stages. State-of-the-art methods have shown that the use of syntactic-type linguistic features provides a sensitive and noninvasive tool for detecting dementia in its early stages. However, these methods lack relevant semantic information. In this work, we propose a novel methodology, based on the semantic features approach, by using sentence embeddings computed by Siamese BERT networks (SBERT), along with support vector machine (SVM), K-nearest neighbors (KNN), random forest, and an artificial neural network (ANN) as classifiers. Our methodology extracted 17 features that provide demographic, lexical, syntactic, and semantic information from 550 oral production samples of elderly controls and people with Alzheimer’s disease, provided by the DementiaBank Pitt Corpus database. To quantify the relevance of the extracted features for the dementia classification task, we calculated the mutual information score, which demonstrates a dependence between our features and the MMSE score. The experimental classification performance metrics, such as the accuracy, precision, recall, and F1 score (77, 80, 80, and 80%, respectively), validate that our methodology performs better than syntax-based methods and the BERT approach when only the linguistic features are used. Full article

Background: We aimed to evaluate personality traits in patients with post-COVID syndrome, as well as the association with neuropsychiatric symptoms present in this disorder. Methods: The Big Five Structure Inventory was administered to 93 consecutive patients with a diagnosis of post-COVID syndrome as defined by the WHO and to demographically matched controls. We also performed a comprehensive evaluation of depression, anxiety, fatigue, sleep quality, cognitive function, and olfactory function. Results: Patients with post-COVID syndrome scored lower for emotional stability, equanimity, positive mood, and self-control. Extraversion, emotional stability, and openness correlated negatively with anxiety and depression levels. Conscientiousness correlated negatively with anxiety. No statistically significant correlations were observed between personality traits and cognitive function, sleep quality, olfactory function, or fatigue. Personality scores explained 36.3% and 41% of the variance in scores on the anxiety and depression scales, respectively. Two personality profiles with lower levels of emotional stability were associated with depression and anxiety. Conclusions: Our study shows higher levels of neuroticism in patients with post-COVID syndrome. Personality traits were predictive of the presence of depression and anxiety, but not cognitive function, sleep quality, or fatigue, in the context of post-COVID syndrome. These findings may have implications for the detection of patients at risk of depression and anxiety in post-COVID syndrome, and for the development of preventive and therapeutic interventions. Full article

Although 20% of the world’s suicides occur in India, suicide prevention efforts in India are lagging (Vijayakumar et al., 2021). Identification of risk factors for suicide in India, as well as the development of accessible interventions to treat these risk factors, could help reduce suicide in India. Interoceptive dysfunction—or an inability to recognize internal sensations in the body—has emerged as a robust correlate of suicidality among studies conducted in the United States. Additionally, a mindfulness-informed intervention designed to reduce interoceptive dysfunction, and thereby suicidality, has yielded promising initial effects in pilot testing (Smith et al., 2021). The current studies sought to replicate these findings in an Indian context. Study 1 (n = 276) found that specific aspects of interoceptive dysfunction were related to current, past, and future likelihood of suicidal ideation. Study 2 (n = 40) was a small, uncontrolled pre-post online pilot of the intervention, Reconnecting to Internal Sensations and Experiences (RISE). The intervention was rated as highly acceptable and demonstrated good retention. Additionally, the intervention was associated with improvements in certain aspects of interoceptive dysfunction and reductions in suicidal ideation and eating pathology. These preliminary results suggest further testing of the intervention among Indian samples is warranted. Full article

Difficulty sleeping in a novel environment is a common phenomenon that is often described as the first night effect (FNE). Previous works have found FNE on sleep architecture and sleep power spectra parameters, especially during non-rapid eye movement (NREM) sleep. However, the impact of FNE on sleep parameters, including local differences in electroencephalographic (EEG) activity across nights, has not been systematically assessed. Here, we performed high-density EEG sleep recordings on 27 healthy individuals on two nights and examined differences in sleep architecture, NREM (stages 2 and 3) EEG power spectra, and NREM power topography across nights. We found higher wakefulness after sleep onset (WASO), reduced sleep efficiency, and less deep NREM sleep (stage 3), along with increased high-frequency NREM EEG power during the first night of sleep, corresponding to small to medium effect sizes (Cohen’s d ≤ 0.5). Furthermore, study individuals showed significantly lower slow-wave activity in right frontal/prefrontal regions as well as higher sigma and beta activities in medial and left frontal/prefrontal areas, yielding medium to large effect sizes (Cohen’s d ≥ 0.5). Altogether, these findings suggest the FNE is characterized by less efficient, more fragmented, shallower sleep that tends to affect especially certain brain regions. The magnitude and specificity of these effects should be considered when designing sleep studies aiming to compare across night effects. Full article

Emerging studies have reported that functional brain networks change with increasing age. Graph theory is applied to understand the age-related differences in brain behavior and function, and functional connectivity between the regions is examined using electroencephalography (EEG). The effect of normal aging on functional networks and inter-regional synchronization during the working memory (WM) state is not well known. In this study, we applied graph theory to investigate the effect of aging on network topology in a resting state and during performing a visual WM task to classify aging EEG signals. We recorded EEGs from 20 healthy middle-aged and 20 healthy elderly subjects with their eyes open, eyes closed, and during a visual WM task. EEG signals were used to construct the functional network; nodes are represented by EEG electrodes; and edges denote the functional connectivity. Graph theory matrices including global efficiency, local efficiency, clustering coefficient, characteristic path length, node strength, node betweenness centrality, and assortativity were calculated to analyze the networks. We applied the three classifiers of K-nearest neighbor (KNN), a support vector machine (SVM), and random forest (RF) to classify both groups. The analyses showed the significantly reduced network topology features in the elderly group. Local efficiency, global efficiency, and clustering coefficient were significantly lower in the elderly group with the eyes-open, eyes-closed, and visual WM task states. KNN achieved its highest accuracy of 98.89% during the visual WM task and depicted better classification performance than other classifiers. Our analysis of functional network connectivity and topological characteristics can be used as an appropriate technique to explore normal age-related changes in the human brain. Full article

This pilot study aimed to investigate the initial effect of a remotely delivered performance-based client-centered intervention on activity performance and participation among adults in the chronic phase after acquired brain injury (ABI). Sixteen participants living at home with little to no assistance in basic daily activities were allocated into intervention or waitlist control groups. Assessments were conducted at the baseline, after the 3-month intervention/wait period, and at a 3-month follow-up. The primary outcomes were activity performance using the Canadian Occupational Performance Measure (COPM) and the Performance Quality Rating Scale (PQRS) and participation using the Mayo-Portland Adaptability Inventory-4 (MPAI-4). The intervention included weekly videoconferencing sessions using the Cognitive Orientation to Daily Occupational Performance approach (tele-CO-OP). The participants identified five functional goals, of which three were directly addressed. Wilcoxon signed-ranks test results showed no significant improvements in the control group at the end of the 3-month wait period. Pooled data from both groups showed significant improvements in COPM scores for trained and untrained goals following the intervention. Significant improvements were also found in the PQRS and MPAI-4 scores. Improvements were partially maintained at follow-up. Our preliminary results suggest that tele-CO-OP may positively impact the lives of adults after ABI who are coping with long-term disability. Full article

As the clinical trial landscape for patients with disorders of consciousness (DoC) expands, consideration of associated ethical challenges and opportunities is of ever-increasing importance. Responsible conduct of research in the vulnerable population of persons with DoC, including those with coma, vegetative state/unresponsive wakefulness syndrome (VS/UWS), minimally conscious state (MCS), covert cortical processing (CCP), and cognitive motor dissociation (CMD), demands proactive deliberation of unique ethical issues that may arise and the adoption of robust protections to safeguard patients, surrogates, and other key stakeholders. Here we identify and critically evaluate four central categories of ethical considerations in clinical trials involving participants with DoC: (1) autonomy, respect for persons and informed consent of individuals with liminal consciousness; (2) balancing unknown benefits and risks, especially considering the epistemological gap between behavior and consciousness that complicates ordinary ascription of subjective states; (3) disclosure to surrogates and clinical teams of investigational results pertaining to consciousness; and (4) justice considerations, including equitable access to clinical trial enrollment across communities and geographies. We outline guiding principles and research opportunities for clinicians, neuroethicists, and researchers engaged in DoC clinical trials to advance ethical study design and deployment in this complex yet crucial area of investigation. Full article

The effects of transcranial alternating current stimulation (tACS) frequency on brain oscillations and cortical excitability are still controversial. Therefore, this study investigated how different tACS frequencies differentially modulate cortical oscillation and inhibition. To do so, we first determined the optimal positioning of tACS electrodes through an electric field simulation constructed from magnetic resonance images. Seven electrode configurations were tested on the electric field of the precentral gyrus (hand motor area). We determined that the Cz-CP1 configuration was optimal, as it resulted in higher electric field values and minimized the intra-individual differences in the electric field. Therefore, tACS was delivered to the hand motor area through this arrangement at a fixed frequency of 10 Hz (alpha-tACS) or 20 Hz (beta-tACS) with a peak-to-peak amplitude of 0.6 mA for 20 min. We found that alpha- and beta-tACS resulted in larger alpha and beta oscillations, respectively, compared with the oscillations observed after sham-tACS. In addition, alpha- and beta-tACS decreased the amplitudes of conditioned motor evoked potentials and increased alpha and beta activity, respectively. Correspondingly, alpha- and beta-tACSs enhanced cortical inhibition. These results show that tACS frequency differentially affects motor cortex oscillation and inhibition. Full article

We aimed to search whether neurological symptoms or signs (NSS) and the MEWS (Modified Early Warning Score) score were associated with in-hospital mortality or oxygen requirement during the first 14 days of hospitalization in COVID-19 patients recruited at the University Hospital in Krakow, Poland. The detailed clinical questionnaires on twenty NSS were either filled out by patients prospectively or retrospectively assessed by neurologists based on daily medical records. NSS were considered high or low-risk if they were associated with increased or decreased mortality in the univariable analysis. This cohort study included 349 patients with COVID-19 (median age 64, interquartile range (51–77), women 54.72%). The presence of high-risk NSS (decreased level of consciousness, delirium, seizures, and symptoms of stroke or transient ischemic attack) or its combination with the absence of low-risk NSS (headache, dizziness, decreased mood, and fatigue) increased the risk of in-hospital mortality in SARS-CoV-2 infection 3.13 and 7.67-fold, respectively. The presence of low-risk NSS decreased the risk of in-hospital mortality in COVID-19 patients more than 6-fold. Death in patients with SARS-CoV-2 infection, apart from NSS, was predicted by older age, neoplasm, and higher MEWS scores on admission. High-risk NSS or their combination with the absence of low-risk NSS increased the risk of oxygen requirement during hospitalization in COVID-19 patients 4.48 and 1.86-fold, respectively. Independent predictors of oxygen therapy during hospitalization in patients with SARS-CoV-2 infection were also older age, male sex, neoplasm, and higher MEWS score on admission. Full article

Motor imagery (MI) refers to the mental rehearsal of movement in the absence of overt motor action, which can activate or inhibit cortical excitability. EEG mu/beta oscillations recorded over the human motor cortex have been shown to be consistently suppressed during both the imagination and performance of movements, although the specific effect on brain function remains to be confirmed. In this study, Granger causality (GC) was used to construct the brain functional network of subjects during motor imagery and resting state based on EEG in order to explore the effects of motor imagery on brain function. Parameters of the brain functional network were compared and analyzed, including degree, clustering coefficient, characteristic path length and global efficiency of EEG mu/beta rhythm in different states. The results showed that the clustering coefficient and efficiency of EEG mu/beta rhythm decreased significantly during motor imagery (p < 0.05), while degree distribution and characteristic path length increased significantly (p < 0.05), mainly concentrated in the frontal lobe and sensorimotor area. For the resting state after motor imagery, the changes of brain functional characteristics were roughly similar to those of the task state. Therefore, it is concluded that motor imagery plays an important role in activation of cortical excitability. Full article

Smell alteration and cognitive impairment are common features of the Long-COVID Syndrome. Mental clouding, often described as brain fog, might affect smell by altering recollection of odors or through a share mechanism of neuroinflammation. We investigated mental clouding, headache, and cognitive function in adult patients with persistent COVID-19 olfactory dysfunction. This multi-center cross-sectional study enrolled 152 adults with self-reported olfactory dysfunction from 3 tertiary centers specialized in COVID-19 olfactory disorders. Inclusion criteria were smell alterations after COVID-19 persisting over 6 months from infection, age >18 and < 65. Exclusion criteria included smell alterations, headache, or memory problems prior to COVID-19 infection. The patients were evaluated by olfactometry, nasal endoscopy, headache scale, cognitive assessment, Mini Mental State Examination (MMSE), and self-reported measures. Smell dysfunction was stratified and classified based on olfactory deficit severity and presence of olfactory distortion (parosmia, cacosmia). Data on smell disorder, mental clouding, MMSE, and headache were analyzed to assess correlations. Among the 152 patients studied, 50 (32.8%) presented with anosmia, 25 (16.4%) with hyposmia, 10 (6.6%) with parosmia/cacosmia, and 58 patients (38.2%) with a combination of hyposmia and parosmia; seven (4.6%) patients suffered from headache exclusively, and two (1.4%) had headache and mental clouding as their primary symptom. Headache was reported by 76 (50%) patients, and mental clouding by 71 (46.7%). The patients reporting headache, mental clouding, or both, had significantly increased risk of suffering from anosmia and/or hyposmia when compared with their counterparts without these neurological symptoms. No patients had reduced MMSE scores. In our cohort of adult patients with post-COVID-19, smell alterations persisting over 6 months, cognitive impairment and headache were associated with more severe olfactory loss, consistent with neuroinflammatory mechanisms mediating a variety of Long-COVID symptoms. Full article

The emergence of cognitive impairment and dementia in people with Lewy body spectrum disorders (LBS) significantly impacts the quality of life of the individual and their care partner. Coping well with the condition may depend, in part, on the degree of psychological resilience or capacity to ‘bounce back’ from adversity. We explored resilience in people with Parkinson’s disease mild cognitive disorder or dementia, or dementia with Lewy bodies, and their care partners, and its relation to outcomes related to their mental well-being and quality of life. This exploratory, cross-sectional study recruited 76 participant-dyads. Resilience, quality of life, depression, anxiety, and relationship satisfaction were evaluated in both members of the dyad. In care partners, care burden and stress were also assessed. Over 70% of both care partners and recipients reported high levels of resilience. Lower resilience in both members of the dyad was associated with higher anxiety and lower quality of life. Additionally, lower resilience in care partners was associated with lower well-being, relationship satisfaction, and higher burden and stress. Resilience in persons with LBS and their care partners is important to consider when assessing mental health, relationship, and care burden outcomes, acting as a focus of intervention to support positive outcomes. Full article

Introduction: The role of increased oxidative stress and alterations to the nitric oxide (NO) pathway have been implicated in major depressive disorder (MDD). The two pathways interact closely with each other but have not been studied simultaneously in MDD. This study aimed to assess and compare the levels of oxidative and nitrosative stress in the neutrophils (PMNs) of drug-naive MDD patients and their first-degree relatives. Methods: 29 drug-naive MDD patients and 27 healthy first-degree relatives and healthy controls aged 18–45 years were included in this study. An assessment of the levels of reactive oxygen species (ROS), nitrites, neuronal NO synthase (nNOS), and myeloperoxidase in PMNs, and cortisol in serum was carried out. Results: Compared to healthy controls, the generation of free radicals, myeloperoxidase activity, and nNOS mRNA expression in PMNs, and cortisol level in serum were significantly higher in drug-naive depression patients. Indeed, increased levels of myeloperoxidase and serum cortisol were also noted in first-degree relatives. The total nitrite content in the PMNs and plasma however was significantly lower in both patients and first-degree relatives. Interestingly, a positive correlation was established in the ROS levels in the PMNs, plasma and neutrophil nitrite, and the serum cortisol level between MDD patients and their first-degree relatives. Conclusion: The results of this study contribute towards a better understanding of the familial association of depressive disorder, and demonstrate for the first time that neutrophil ROS/RNS, plasma nitrite, and serum cortisol levels are positively correlated between MDD patients and their first-degree relatives. However, further studies in larger, more diverse samples are needed to extend these pathways as potential biomarkers to identify persons at high risk for psychopathology at an early stage. Full article

Due to phoenixin’s role in restraint stress and glucocorticoid stress, as well as its recently shown effects on the inflammasome, we aimed to investigate the effects of lipopolysaccharide (LPS)-induced inflammatory stress on the activity of brain nuclei-expressing phoenixin. Male Sprague Dawley rats (n = 6/group) were intraperitoneally injected with either LPS or control (saline). Brains were processed for c-Fos and phoenixin immunohistochemistry and the resulting slides were evaluated using ImageJ software. c-Fos was counted and phoenixin was evaluated using densitometry. LPS stress significantly increased c-Fos expression in the central amygdaloid nucleus (CeM, 7.2-fold), supraoptic nucleus (SON, 34.8 ± 17.3 vs. 0.0 ± 0.0), arcuate nucleus (Arc, 4.9-fold), raphe pallidus (RPa, 5.1-fold), bed nucleus of the stria terminalis (BSt, 5.9-fold), dorsal motor nucleus of the vagus nerve (DMN, 89-fold), and medial part of the nucleus of the solitary tract (mNTS, 121-fold) compared to the control-injected group (p < 0.05). Phoenixin expression also significantly increased in the CeM (1.2-fold), SON (1.5-fold), RPa (1.3-fold), DMN (1.3-fold), and mNTS (1.9-fold, p < 0.05), leading to a positive correlation between c-Fos and phoenixin in the RPa, BSt, and mNTS (p < 0.05). In conclusion, LPS stress induces a significant increase in activity in phoenixin immunoreactive brain nuclei that is distinctively different from restraint stress. Full article

Sensory processing differences are an established feature of both syndromic and non-syndromic Autism Spectrum Disorders (ASDs). Significant work has been carried out to characterize and classify specific sensory profiles in non-syndromic autism. However, it is not known if syndromic autism disorders, such as Phelan-McDermid Syndrome (PMD) or SYNGAP1-related Intellectual Disability (SYNGAP1-ID), have unique sensory phenotypes. Understanding the sensory features of these disorders is important for providing appropriate care and for understanding their underlying mechanisms. Our objective in this work was to determine the sensory processing abnormalities present in two syndromic ASDs: Phelan-McDermid Syndrome and SYNGAP1-related Intellectual Disability. Using a standardized instrument, the Short Sensory Profile-2, we characterized sensory features in 41 patients with PMD and 24 patients with SYNGAP1-ID, and sub-scores were then calculated for seeking, avoiding, sensitivity and registration, as well as overall sensory and behavior scores. We found both patient groups exhibited atypical sensory features, including high scores in the areas of avoiding and seeking. Thus, we discovered significant sensory processing abnormalities are common in these syndromic ASDs. Measurements of sensory processing could serve as useful clinical endpoints for trials of novel therapeutics for these populations. Full article

Background: Epilepsy surgery failure is not uncommon, with several explanations having been proposed. In this series, we detail cases of epilepsy surgery failure subsequently attributed to insular involvement. Methods: We retrospectively identified patients investigated at the epilepsy monitoring units of two Canadian tertiary care centers (2004–2020). Included patients were adults who had undergone epilepsy surgeries with recurrence of seizures post-operatively and who were subsequently determined to have an insular epileptogenic focus. Clinical, electrophysiological, neuroimaging, and surgical data were synthesized. Results: We present 14 patients who demonstrated insular epileptic activity post-surgery-failure as detected by intracranial EEG, MEG, or seizure improvement after insular resection. Seven patients had manifestations evoking possible insular involvement prior to their first surgery. Most patients (8/14) had initial surgeries targeting the temporal lobe. Seizure recurrence ranged from the immediate post-operative period to one year. The main modality used to determine insular involvement was MEG (8/14). Nine patients underwent re-operations that included insular resection; seven achieved a favorable post-operative outcome (Engel I or II). Conclusions: Our series suggests that lowering the threshold for suspecting insular epilepsy may be necessary to improve epilepsy surgery outcomes. Detecting insular epilepsy post-surgery-failure may allow for re-operations which may lead to good outcomes. Full article

The search for a biological marker predicting the future failure or success of electroconvulsive therapy (ECT) remains highly challenging for patients with treatment-resistant depression. Evidence suggests that Brain-Derived Neurotrophic Factor (BDNF), a protein known to be involved in brain plasticity mechanisms, can play a key role in both the clinical efficacy of ECT and the pathophysiology of depressive disorders. We hypothesized that mature BDNF (mBDNF), an isoform of BDNF involved in the neural plasticity and survival of neural networks, might be a good candidate for predicting the efficacy of ECT. Total BDNF (tBDNF) and mBDNF levels were measured in 23 patients with severe treatment-resistant depression before (baseline) they received a course of ECT. More precisely, tBDNF and mBDNF measured before ECT were compared between patients who achieved the criteria of remission after the ECT course (remitters, n = 7) and those who did not (non-remitters, n = 16). We found that at baseline, future remitters displayed significantly higher mBDNF levels than future non-remitters (p = 0.04). No differences were observed regarding tBDNF levels at baseline. The multiple logistic regression model controlled for age and sex revealed that having a higher baseline mBDNF level was significantly associated with future remission after ECT sessions (odd ratio = 1.38; 95% confidence interval = 1.07–2.02, p = 0.04). Despite the limitations of the study, current findings provide additional elements regarding the major role of BDNF and especially the mBDNF isoform in the clinical response to ECT in major depression. Full article

Research has shown that dyslexia and attention deficit (hyperactivity) disorder (AD(H)D) are characterized by specific neuroanatomical and neurofunctional differences in the auditory cortex. These neurofunctional characteristics in children with ADHD, ADD and dyslexia are linked to distinct differences in music perception. Group-specific differences in the musical performance of patients with ADHD, ADD and dyslexia have not been investigated in detail so far. We investigated the musical performance and neurophysiological correlates of 21 adolescents with dyslexia, 19 with ADHD, 28 with ADD and 28 age-matched, unaffected controls using a music performance assessment scale and magnetoencephalography (MEG). Musical experts independently assessed pitch and rhythmic accuracy, intonation, improvisation skills and musical expression. Compared to dyslexic adolescents, controls as well as adolescents with ADHD and ADD performed better in rhythmic reproduction, rhythmic improvisation and musical expression. Controls were significantly better in rhythmic reproduction than adolescents with ADD and scored higher in rhythmic and pitch improvisation than adolescents with ADHD. Adolescents with ADD and controls scored better in pitch reproduction than dyslexic adolescents. In pitch improvisation, the ADD group performed better than the ADHD group, and controls scored better than dyslexic adolescents. Discriminant analysis revealed that rhythmic improvisation and musical expression discriminate the dyslexic group from controls and adolescents with ADHD and ADD. A second discriminant analysis based on MEG variables showed that absolute P1 latency asynchrony |R-L| distinguishes the control group from the disorder groups best, while P1 and N1 latencies averaged across hemispheres separate the control, ADD and ADHD groups from the dyslexic group. Furthermore, rhythmic improvisation was negatively correlated with auditory-evoked P1 and N1 latencies, pointing in the following direction: the earlier the P1 and N1 latencies (mean), the better the rhythmic improvisation. These findings provide novel insight into the differences between music processing and performance in adolescents with and without neurodevelopmental disorders. A better understanding of these differences may help to develop tailored preventions or therapeutic interventions. Full article

The olfactory bulb (OB) plays a key role in the processing of olfactory information. A large body of research has shown that OB volumes correlate with olfactory function, which provides diagnostic and prognostic information in olfactory dysfunction. Still, the potential value of the OB shape remains unclear. Based on our clinical experience we hypothesized that the shape of the OB predicts olfactory function, and that it is linked to olfactory loss, age, and gender. The aim of this study was to produce a classification of OB shape in the human brain, scalable to clinical and research applications. Results from patients with the five most frequent causes of olfactory dysfunction (n = 192) as well as age/gender-matched healthy controls (n = 77) were included. Olfactory function was examined in great detail using the extended “Sniffin’ Sticks” test. A high-resolution structural T2-weighted MRI scan was obtained for all. The planimetric contours (surface in mm²) of OB were delineated manually, and then all surfaces were added and multiplied to obtain the OB volume in mm³. OB shapes were outlined manually and characterized on a selected slice through the posterior coronal plane tangential to the eyeballs. We looked at OB shapes in terms of convexity and defined two patterns/seven categories based on OB contours: convex (olive, circle, and plano-convex) and non-convex (banana, irregular, plane, and scattered). Categorization of OB shapes is possible with a substantial inter-rater agreement (Cohen’s Kappa = 0.73). Our results suggested that non-convex OB patterns were significantly more often observed in patients than in controls. OB shapes were correlated with olfactory function in the whole group, independent of age, gender, and OB volume. OB shapes seemed to change with age in healthy subjects. Importantly, the results indicated that OB shapes were associated with certain causes of olfactory disorders, i.e., an irregular OB shape was significantly more often observed in post-traumatic olfactory loss. Our study provides evidence that the shape of the OB can be used as a biomarker for olfactory dysfunction. Full article

Parkinson’s disease (PD) is a chronic, progressive, neurodegenerative disease involving both motor and non-motor symptoms (NMS). In the late stage of the disease, Hoehn and Yahr (HY) stages IV-V, the symptomatology is often severe and patients become increasingly dependent on help in their daily life, resulting in an increased burden for the informal caregivers. To assess the implications of the caregiver burden, caregiver quality of life (QoL) was assessed in 74 informal caregivers to patients in late stage PD, by the Alzheimer’s Patient Partners Life Impact Questionnaire (APPLIQue), which has been found useful also in PD. The majority of caregivers were the spouse/partner. Individual items provided information on which aspects of caregiver burden were the most common, i.e., items: “feel guilty if not there” (71% affirmed), “situation wears me down” (65% affirmed) and “always on my mind” (61% affirmed). In simple linear regression analyses, female patient gender (p = 0.007), better cognition (p = 0.004), lower NMS burden (p = 0.012) and not being the partner (p = 0.022) were associated with better caregiver QoL. Multivariable linear regression analyses identified better cognition (p = 0.004) and female patient gender (p = 0.035) as independently associated with better informal caregiver QoL. Identifying and treating NMS as well as recognizing and alleviating caregiver burden seem essential to enhance QoL for both patients and caregivers in late stage PD. Full article

Due to their similar imaging features, high-grade gliomas (HGGs) and solitary brain metastases (BMs) can be easily misclassified. The peritumoral zone (PZ) of HGGs develops neoplastic cell infiltration, while in BMs the PZ contains pure vasogenic edema. As the two PZs cannot be differentiated macroscopically, this study investigated whether computed tomography (CT)-based texture analysis (TA) of the PZ can reflect the histological difference between the two entities. Thirty-six patients with solitary brain tumors (HGGs, n = 17; BMs, n = 19) that underwent CT examinations were retrospectively included in this pilot study. TA of the PZ was analyzed using dedicated software (MaZda version 5). Univariate, multivariate, and receiver operating characteristics analyses were used to identify the best-suited parameters for distinguishing between the two groups. Seven texture parameters were able to differentiate between HGGs and BMs with variable sensitivity (56.67–96.67%) and specificity (69.23–100%) rates. Their combined ability successfully identified HGGs with 77.9–99.2% sensitivity and 75.3–100% specificity. In conclusion, the CT-based TA can be a useful tool for differentiating between primary and secondary malignancies. The TA features indicate a more heterogenous content of the HGGs’ PZ, possibly due to the local infiltration of neoplastic cells. Full article

Current literature supports the notion that the recognition of objects, when visually presented, is sub-served by neural structures different from those responsible for the semantic processing of their nouns. However, embodiment foresees that processing observed objects and their verbal labels should share similar neural mechanisms. In a combined behavioral and MEG study, we compared the modulation of motor responses and cortical rhythms during the processing of graspable natural objects and tools, either verbally or pictorially presented. Our findings demonstrate that conveying meaning to an observed object or processing its noun similarly modulates both motor responses and cortical rhythms; being natural graspable objects and tools differently represented in the brain, they affect in a different manner both behavioral and MEG findings, independent of presentation modality. These results provide experimental evidence that neural substrates responsible for conveying meaning to objects overlap with those where the object is represented, thus supporting an embodied view of semantic processing. Full article

Autism spectrum disorder (ASD) is a complicated neurological developmental disorder that manifests itself in a variety of ways. The child diagnosed with ASD and their parents’ daily lives can be dramatically improved with early diagnosis and appropriate medical intervention. The applicability of static features extracted from autistic children’s face photographs as a biomarker to distinguish them from typically developing children is investigated in this study paper. We used five pre-trained CNN models: MobileNet, Xception, EfficientNetB0, EfficientNetB1, and EfficientNetB2 as feature extractors and a DNN model as a binary classifier to identify autism in children accurately. We used a publicly available dataset to train the suggested models, which consisted of face pictures of children diagnosed with autism and controls classed as autistic and non-autistic. The Xception model outperformed the others, with an AUC of 96.63%, a sensitivity of 88.46%, and an NPV of 88%. EfficientNetB0 produced a consistent prediction score of 59% for autistic and non-autistic groups with a 95% confidence level. Full article

Parkinson’s disease (PD) is a progressive neurodegenerative disorder resulting in reduced health-related quality of life (HR-QoL) of people with PD (PwP) and their caregivers. Furthermore, there is an accumulating burden on caregivers of patients in advanced stages of the disease. In previous studies, motor- and non-motor-symptoms of PwP have been identified to contribute to reduced HR-QoL and an increased caregiver burden. This cross-sectional observational study aimed to study the influence of neuropsychiatric symptoms measured with the Scale for Evaluation of Neuropsychiatric Disorders in Parkinson’s Disease (SEND-PD) questionnaire on the HR-QoL of PwP, as well as the caregiver burden. Analyses revealed a significant association between SEND-PD subscale mood/apathy and reduced HR-QoL in PwP, measured by the Parkinson’s disease quality of life questionnaire (PDQ-8) (p < 0.001). Furthermore, mood/apathy was significantly correlated with caregiver burden (p = 0.001) in the multiple linear regression analysis. Hence, neuropsychiatric symptoms were found to have a profound impact on the HR-QoL of PwP, as well as on caregiver burden. Since neuropsychiatric symptoms were one of the main predictors for caregiver burden, physicians of PwP should treat these symptoms to stabilize caregiver burden, as well as HR-QoL in PwP and their caregivers. Full article