Editor’s Choice Articles

The roles of perinatal development, intracellular calcium [Ca²⁺]i, and synaptogenesis disruption are not novel in the autism/ASD literature. The focus on six mechanisms controlling synaptogenesis, each regulated by [Ca²⁺]i, and each aberrant in ASDs is novel. The model presented here predicts that autism epidemic causation involves central roles of both electromagnetic fields (EMFs) and chemicals. EMFs act via voltage-gated calcium channel (VGCC) activation and [Ca²⁺]i elevation. A total of 15 autism-implicated chemical classes each act to produce [Ca²⁺]i elevation, 12 acting via NMDA receptor activation, and three acting via other mechanisms. The chronic nature of ASDs is explained via NO/ONOO(-) vicious cycle elevation and MeCP2 epigenetic dysfunction. Genetic causation often also involves [Ca²⁺]i elevation or other impacts on synaptogenesis. The literature examining each of these steps is systematically examined and found to be consistent with predictions. Approaches that may be sed for ASD prevention or treatment are discussed in connection with this special issue: The current situation and prospects for children with ASDs. Such approaches include EMF, chemical avoidance, and using nutrients and other agents to raise the levels of Nrf2. An enriched environment, vitamin D, magnesium, and omega-3s in fish oil may also be helpful. Full article

The acquisition of skills, such as learning to play a musical instrument, involves various phases that make specific demands on the learner. Knowledge of the cognitive and motor contributions during learning phases can be helpful in developing effective and targeted interventions for healthy aging. Eighty-six healthy older participants underwent an extensive cognitive, motoric, and musical test battery. Within one session, one piano-related and one music-independent movement sequence were both learned. We tested the associations between skill performance and cognito-motor abilities with Bayesian mixed models accounting for individual learning rates. Results showed that performance was positively associated with all cognito-motor abilities. Learning a piano-related task was characterized by relatively strong initial associations between performance and abilities. These associations then weakened considerably before increasing exponentially from the second trial onwards, approaching a plateau. Similar performance–ability relationships were detected in the course of learning a music-unrelated motor task. Positive performance–ability associations emphasize the potential of learning new skills to produce positive cognitive and motor transfer effects. Consistent high-performance tasks that demand maximum effort from the participants could be very effective. However, interventions should be sufficiently long so that the transfer potential can be fully exploited. Full article

Background: Autism spectrum disorder (ASD) and obsessive compulsive disorder (OCD) are two common and impairing neurodevelopmental conditions with partial symptomatic overlap. The aim of this study is to systematically and meta-analytically examine the following: (i) the prevalence of an OCD diagnosis among young people with ASD, (ii) the prevalence of an ASD diagnosis among young people with OCD, and (iii) the clinical and therapeutic implications of such comorbidity. Method: A multistep literature search was performed from database inception until 17 November 2023. This PRISMA/MOOSE-compliant systematic review, registered in PROSPERO (CRD42023480543), identified studies reporting on the prevalence, sociodemographic, psychopathologic, prognostic, and therapeutic correlates of OCD and ASD concurrence in children and adolescents. A quantitative meta-analysis with random effects was conducted to analyse the pooled prevalence of OCD among samples with a mean age of < 18 years old with ASD and the prevalence of ASD among individuals under 18 with OCD. Sensitivity analyses were performed to investigate the effect of diagnostic criteria and different continents. Meta-regression analyses were conducted to examine the effect of gender, age, IQ, and OCD severity scores. A narrative review of the clinical and therapeutical implications of the comorbidity was provided. Results: 42 studies were selected for the systematic review (SR), and 31 of them were also included in one of the meta-analyses. The pooled prevalence of OCD among ASD youth samples (n = 8916, mean age = 10.6 ± 1.6; 16.4% female) was 11.6% (95% confidence intervals [CI] = 6.9%; 18.8%), and the pooled prevalence of ASD among OCD children and adolescent samples (n = 6209, mean age = 14.1 ± 1.4; 45.7% female) was 9.5% (95% CI = 6.0%; 14.7%). Meta-regressions found a statistically higher prevalence of ASD among samples with a lower prevalence of females (β = −4.7; 95%CI = −8.6; −0.8). Children with both OCD and ASD present higher rates of functional impairment, psychopathology, and other comorbidities, compared to youth with either of the disorders alone. Conclusions: OCD and ASD are highly concurrent conditions in youth, with symptomatic, prognostic, severity, and therapeutic implications. Future research should focus on conducting longitudinal cohort studies prospectively to determine development trajectories, along with randomized controlled trials to assess the efficacy of specific therapeutic interventions. Full article

Transcranial direct current stimulation (tDCS) is a non-invasive and painless technique of brain neuromodulation that applies a low-intensity galvanic current to the scalp with the aim of stimulating specific areas of the brain. Preliminary investigations have indicated the potential therapeutic efficacy of multisession tDCS applied to the auditory cortex (AC) in the treatment of chronic tinnitus. The aim of this study was to explore the therapeutic effects of repeated sessions of bilateral tDCS targeting the AC on chronic tinnitus. A double-blinded randomized placebo-controlled trial was conducted on patients (n = 48) with chronic intractable tinnitus (>2 years duration). Participants were randomly allocated to two groups: one receiving tDCS (n = 26), with the anode/cathode placed over the left/right AC, and the other receiving a placebo treatment (n = 22). A 20 min daily session of 2 mA current was administered for five consecutive days per week over two consecutive weeks, employing 35 cm² electrodes. Tinnitus handicap inventory (THI) scores, tinnitus loudness, and tinnitus distress were measured using a visual analogue scale (VAS), and were assessed before intervention, immediately after, and at one-month follow-up. Anodal tDCS significantly reduced THI from 72.93 ± 10.11 score to 46.40 ± 15.36 after the last session and 49.68 ± 14.49 at one-month follow-up in 18 out of 25 participants (p < 0.001). The risk ratio (RR) of presenting an improvement of ≥20 points in the THI after the last session was 10.8 in patients treated with tDCS. Statistically significant reductions were observed in distress VAS and loudness VAS (p < 0.001). No statistically significant differences in the control group were observed. Variables such as age, gender, duration of tinnitus, laterality of tinnitus, baseline THI scores, and baseline distress and loudness VAS scores did not demonstrate significant correlations with treatment response. Repeated sessions of bilateral AC tDCS may potentially serve as a therapeutic modality for chronic tinnitus. Full article

Background: Cluster headache (CH) is a debilitating condition, but current therapies leave CH patients in pain. The extent of this problem in Sweden is unknown. Methods: An anonymized questionnaire was sent to 479 Swedish CH patients to investigate patterns and perceived effects of treatments. Results: Three hundred fourteen answers were analyzed. The population was representative regarding age of onset and sex. Less than half (46%) were satisfied with their abortive treatments, 19% terminated functioning abortive treatments due to side effects. Additionally, 17% of chronic CH patients had not tried the first-line preventive drug verapamil. A small subset had tried illicit substances to treat their CH (0–8% depending on substance). Notably, psilocybin was reported effective as an abortive treatment by 100% (n = 8), and with some level of effect as a preventive treatment by 92% (n = 12). For verapamil, some level of preventive effect was reported among 68% (n = 85). Conclusions: Our descriptive data illustrate that many Swedish CH patients are undertreated, lack functional therapies, and experience side effects. Further studies are warranted to search for new treatment strategies as well as a revision of current treatment guidelines with the aim of reducing patient disease burden to the greatest extent possible. Full article

Syndromic autism refers to autism spectrum disorder diagnosed in the context of a known genetic syndrome. The specific manifestations of any one of these syndromic autisms are related to a clinically defined genetic syndrome that can be traced to certain genes and variants, genetic deletions, or duplications at the chromosome level. The genetic mutations or defects in single genes associated with these genetic disorders result in a significant elevation of risk for developing autism relative to the general population and are related to recurrence with inheritance patterns. Additionally, these syndromes are associated with typical behavioral characteristics or phenotypes as well as an increased risk for specific behavioral or psychiatric disorders and clinical findings. Knowledge of these associations helps guide clinicians in identifying potentially treatable conditions that can help to improve the lives of affected patients and their families. Full article

Alcohol use disorder (AUD) is a significant contributor to morbidity and mortality in the United States. It contributes to over 140,000 annual deaths, to over 200 related diseases and health conditions globally, and accounts for 5.1% of the global disease burden. Despite its substantial impact, AUD remains undertreated, marked by a scarcity of approved medications. This paper explores the current treatment landscape and novel strategies for both alcohol withdrawal syndrome and AUD. Promising results, including the use of psychedelics alongside psychotherapy, noninvasive neural-circuit-based interventions, phosphodiesterase-4 inhibitors, and GLP-1 receptor agonists, have emerged from recent studies. While these advancements show potential, further research is crucial for a comprehensive understanding of their effectiveness. The clear shortage of approved medications and other treatment modalities underscores the pressing need for ongoing research. Full article

Quantifying saccadic eye movements can assist in identifying dysfunctional brain networks in both healthy and diseased people. Infrared Oculography is a simple and non-invasive approach to capturing and quantifying saccades, providing information that might aid in diagnosis and outcome assessments. The effect of spinal manipulation on quantified saccadic performance parameters has not been fully studied despite known post-manipulative effects on the brain and brainstem regions controlling them. This case study investigates spinal manipulation’s immediate and long-term effects on saccadic eye movements by quantifying the saccades of a male patient diagnosed with post-concussion syndrome. The patient performed horizontal saccades that were quantified before and immediately following cervical spinal manipulation both at the case study’s start and following a 2-week interim, during which the subject received six manipulative treatments. Immediate and long-term post-manipulative effects were observed, and the results revealed various post-manipulative effects across all quantified parameters in addition to between right and leftward saccades. The immediate post-manipulative effect was greatest at the case study’s onset, while the long-term right and leftward saccadic symmetry were most affected. The observations in this case study demonstrate that cervical spinal manipulation influences saccadic eye movements, providing new insights into its central neurological effects and therapeutic applications beyond its most commonly known use in pain management. More importantly, it encourages scientists to undertake further clinical investigations on wider scales. Full article

Background: Speech-sound disorders (SSD) have been linked to auditory processing difficulties, and auditory processing disorders (APD) have been related to phonological awareness and literacy development. To this date, there has not been a systematic literature review investigating the results of psychophysiology and language assessments related to SSD and APD in children. Methods: The literature search was conducted in PubMed, Medline EBSCO, and Scopus to identify studies with children diagnosed/suspected of having APDs and SSDs. The quality of methodology in the selected articles was evaluated with the Newcastle Ottawa Scale. Results: Seven out of 378 relevant studies met the selection criteria. The findings were summarized for children with SSD and APD based on (a) metalinguistic and literacy skills, (b) cognitive abilities, and (c) temporal processing abilities. Three articles indicated that children with APD and SSD exhibit lower temporal task accuracy and reaction time. In two studies, children with SSD exhibited lower scores in discrimination, sequencing, and recall of brief stimuli in rapid succession. Conclusions: This review revealed associations between SSD severity and APD that may underline low performance in metalinguistic skills. Diagnostic assessments have been proposed based on the review to adequately identify children with SSD and APD and provide useful information for more suitable intervention. Full article

Sensory processing is a fundamental aspect of the nervous system that plays a pivotal role in the cognitive decline observed in older individuals with dementia. The “sensory diet”, derived from sensory integration theory, may provide a tailored approach to modulating sensory experiences and triggering neuroplastic changes in the brain in individuals with dementia. Therefore, this review aimed to investigate the current knowledge regarding the sensory diet and its potential application to dementia. This review encompassed an extensive search across multiple databases, including PubMed, Google Scholar, covering articles published from 2010 to 2023. Keywords such as “sensory integration”, “sensory modulation”, “healthy aging”, and “dementia” were utilized to identify relevant studies. The types of materials retrieved included peer-reviewed articles, systematic reviews, and meta-analyses, ensuring a comprehensive overview of the current research landscape. This article offers a comprehensive exploration of the effectiveness of sensory diets such as tactile stimulation, auditory therapies, and visual interventions, which have demonstrated noteworthy efficacy in addressing challenges linked to aging and dementia. Research findings consistently report positive outcomes, such as improved cognitive function, elevated emotional well-being, and enhanced overall quality of life in older individuals. Furthermore, we found that the integration of sensory diets with the metaverse, augmented reality, and virtual reality opens up personalized experiences, fostering cognitive stimulation and emotional well-being for individuals during aging. Therefore, we conclude that customized sensory diets, based on interdisciplinary cooperation and leveraging technological advancements, are effective in optimizing sensory processing and improve the overall well-being of older individuals contending with sensory modulation challenges and dementia. Full article

Objective: To explore the association between the apolipoprotein E (APOE) genotype and objectively assessed cognitive function. Methods: In this cross-sectional study, 537 participants underwent a neuropsychological assessment for cognitive function and blood testing for APOE genotype. Based on cognitive test results, participants were stratified into two cohorts: Cognitively Unimpaired participants (CU) and Cognitively Impaired participants (CI). The CI group was further divided into Mild Cognitive Impairment (MCI) and Alzheimer’s Disease (AD). Furthermore, we conducted age stratification, categorizing participants into three age groups: age 1: <65 years, age 2: 65–75 years, and age 3: >75 years. We assessed the disparities in cognitive function associated with ε4 carrier status across different age brackets. Plasma amyloid-β levels were measured in a cohort of 294 participants to investigate potential interactions involving ε4 carrier status, diagnosis, sex, or plasma markers. Results: The APOE genotypic distribution among the 537 participants was characterized as follows: ε2/ε2 (5 participants), ε2/ε3 (67), ε2/ε4 (13), ε3/ε3 (330), ε3/ε4 (113), and ε4/ε4 (9). Allele frequencies were: ε3 at 78.21%, ε4 at 13.41%, and ε2 at 8.38%. Notably, the ε4 carrier frequency was markedly elevated in the AD group at 81.8% when compared to MCI at 32.8% and CU at 21.3% (p < 0.05). Within the Cognitively Unimpaired (CU) cohort, the sole discernible contrast between ε4+ and ε4− emerged in STT-B (p < 0.05). Within the CI group, ε4 carriers showed statistically poorer scores as compared to non-ε4 carriers in several cognitive tests (p < 0.05). Age stratification result revealed that, among ε4 carriers, cognitive function scores within the age 3 group were significantly inferior to those of age 1 and age 2 groups (p < 0.05). Plasma amyloid-β detection was applied to the 294 participants. We tested plasma amyloid-β (Aβ42) and plasma amyloid-β (Aβ40) levels and calculated the Aβ42/Aβ40 ratio. We found that among female ε4 carriers, both Aβ42 and the Aβ42/Aβ40 ratio were notably lower than their male counterparts (p < 0.05). Conclusions: The ε3/ε3 was the most prevalent among participants, succeeded by ε3/ε4 and ε2/ε3. The least prevalent were ε2/ε4, ε4/ε4, and ε2/ε2 genotypes. The ε3 was predominant, followed by the ε4 and ε2. Individuals with the ε4 allele exhibited significant cognitive impairment, with an especially high prevalence in AD group at 81.8%. The study unveils a pronounced correlation between the ε4 allele and cognitive deficits, implying its potential role in the advancement and severity of cognitive disorders, notably Alzheimer’s disease. Cognitive function declines with age in individuals carrying the ε4, and women are more affected by ε4. Full article

About one-third of stroke survivors present unilateral spatial neglect (USN) that negatively impacts the rehabilitation outcome. We reported the study protocol and usability results of an eye-tracking (ET) biofeedback immersive virtual reality (iVR) protocol. Healthy controls and stroke patients with and without USN underwent a single session of the three iVR tasks. The system usability scale (SUS), adverse events (AEs), and ET data were collected and analyzed via parametric analysis. Twelve healthy controls (six young adults and six older adults) and seven patients with a diagnosis of single ischemic stroke (four without USN and three with confirmed diagnosis of USN) completed the usability investigation. SUS results showed good acceptability of the system for healthy controls and stroke patients without USN. ET results showed a lower performance for patients with USN concerning healthy controls and stroke patients without USN, in particular in the exploration of the left visual field. The results showed that the proposed iVR-ET biofeedback protocol is a safe and well-tolerated technique in patients with USN. The real-time feedback can induce a performance response supporting its investigation such as a treatment approach. Full article

Mild cognitive impairment (MCI) is a transitional or prodromal stage of dementia in which autonomies are largely preserved (autonomies are not particularly affected). However, this condition may entail a depletion of decision-making (DM) abilities likely due to a gradual deterioration of the prefrontal cortex and subcortical brain areas underlying cognitive–emotional processing. Given the clinical implications of a decline in self-determination observed in some MCI sufferers, the present systematic review was aimed at investigating the literature addressing DM processes in patients with MCI, consistent with PRISMA guidelines. The six online databases inquired yielded 1689 research articles that were screened and then assessed based on eligibility and quality criteria. As a result, 41 studies were included and classified following the PICOS framework. Overall, patients with MCI who underwent neuropsychological assessment were found to be slightly or moderately impaired in DM abilities related to financial management, medical adherence, specific cognitive performances, risky conditions, and especially uncertain life circumstances. Comparative cross-sectional studies indicated not only mid-stage cognitive functioning in MCI but also borderline or deficit DM patterns evaluated through different tasks and procedures. Further research addressing MCI profiles suggested an association between explicit memory, executive functions, and DM performance. These findings highlight the diversity of MCI manifestations, in addition to the critical importance of DM features and correlates in patients’ daily functioning. Due to a lack of consensus on both MCI and DM, this review paper sought to shed light on assessment and intervention strategies accounting for the interplay between emotion, motivation, and learning to foster DM in cognitively impaired individuals. Full article

Objectives: The temporal and spatial information of electroencephalogram (EEG) signals is crucial for recognizing features in emotion classification models, but it excessively relies on manual feature extraction. The transformer model has the capability of performing automatic feature extraction; however, its potential has not been fully explored in the classification of emotion-related EEG signals. To address these challenges, the present study proposes a novel model based on transformer and convolutional neural networks (TCNN) for EEG spatial–temporal (EEG ST) feature learning to automatic emotion classification. Methods: The proposed EEG ST-TCNN model utilizes position encoding (PE) and multi-head attention to perceive channel positions and timing information in EEG signals. Two parallel transformer encoders in the model are used to extract spatial and temporal features from emotion-related EEG signals, and a CNN is used to aggregate the EEG’s spatial and temporal features, which are subsequently classified using Softmax. Results: The proposed EEG ST-TCNN model achieved an accuracy of 96.67% on the SEED dataset and accuracies of 95.73%, 96.95%, and 96.34% for the arousal–valence, arousal, and valence dimensions, respectively, for the DEAP dataset. Conclusions: The results demonstrate the effectiveness of the proposed ST-TCNN model, with superior performance in emotion classification compared to recent relevant studies. Significance: The proposed EEG ST-TCNN model has the potential to be used for EEG-based automatic emotion recognition. Full article

Hypnosis, a time-honored therapeutic approach, has gained widespread recognition for its effectiveness in addressing a range of psychological and somatic disorders. While its primary effects are mediated by central top–down mechanisms, hypnosis also exerts peripheral influence by modulating the autonomic nervous system (ANS). Psychophysiological measures, such as heart rate (HR) and its variability (HRV), electrodermal activity (EDA), respiratory rate (RR), and the analgesia nociceptive index (ANI), serve as reliable indicators of ANS activity. Studies have consistently demonstrated hypnosis’ ability to significantly impact ANS functions, lowering sympathetic activity and enhancing parasympathetic tone. This effect is particularly pronounced during relaxation procedures and is influenced by mediating factors like hypnotizability and task conditions. Despite methodological limitations, this review highlights the potential of enhanced ANS modulation through hypnosis, including its connections to the central nervous system (CNS), to optimize therapeutic outcomes in patients with psychosomatic disorders associated with ANS dysfunction. Full article

Objective: This study aims to provide an overview of pharmacological trials that examine the neurocognitive effects of psychedelics among healthy individuals and patients with post-traumatic stress disorder (PTSD) or major depressive disorder (MDD). Methods: The Preferred Reporting Items for Systematic Reviews (PRISMA) was used as a guide to structure and report the findings for this review. A literature search included the MEDLINE database up until December 2022. We included randomized or open-label human studies of MDMA, psilocybin, mescaline, LSD, DMT, or cannabis reporting non-emotionally charged neurocognitive outcomes (“cold cognition”) measured through validated neuropsychological tests. Results: A total of 43 full-text papers on MDMA (15), cannabis (12), LSD (6), psilocybin (9), DMT/ayahuasca (1), and mescaline (0) were included, mostly on healthy subjects. A single article on MDMA’s effects on cognition in subjects with PTSD was included; there were no studies on psychedelics and neurocognition in MDD. Most of the studies on healthy subjects reported detrimental or neutral effects on cognition during the peak effect of psychedelics with a few exceptions (e.g., MDMA improved psychomotor function). Performance on the type of neurocognitive dimension (e.g., attention, memory, executive function, psychomotor) varies by type of psychedelic, dosage, and cognitive testing. Conclusions: Small samples and a lack of uniformed methods across studies preclude unequivocal conclusions on whether psychedelics enhance, decrease, or have no significant effect on cognitive performance. It is foreseen that psychedelics will soon become an available treatment for various psychiatric disorders. The acute and long-term effects on cognition caused by psychedelics should be assessed in future studies. Full article

While cognitive abilities in people with multiple sclerosis (PwMS) have been studied in detail, little is known about linguistic abilities in PwMS and their relation to cognitive impairment. In this cross-sectional explorative study, we aim to investigate the morphosyntactic abilities of PwMS alongside their cognitive performance. Furthermore, we explore the effect of clinical factors, namely, the disease duration and MS type, on the linguistic and cognitive performance of PwMS. By so doing, we aim to shed light on neurocognitive and clinical correlates of linguistic performance in PwMS. We included 78 patients and 78 age-, sex- and education-matched healthy individuals. All participants were additionally administered the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) battery, a verbal short-term memory task (non-word repetition) and questionnaires about mood, fatigue and quality of life. In addition, they underwent examinations with morphology and syntax tasks. PwMS were found to be impaired in morphology (past tense) and selectively impaired in syntax alongside cognitive impairments. Disease duration had the main impact on cognitive abilities. The MS type selectively impacted linguistic abilities, as shown by the remarkably deficient performance of the MS individuals with the progressive disease subtype. Linguistic impairments were predicted by only one measure of the BICAM test, namely, the Symbol Digit Modalities Test (SDMT), a measure of cognitive processing speed. Overall, this study contributes to the better understanding of the linguistic profile of PwMS by reporting selective deficits in their morphological and syntactical abilities. Furthermore, it provides insights into the clinical and cognitive correlates of linguistic performance. By so doing, it suggests clinical implications for the development of intervention programs for PwMS. Full article

Cannabis use disorder (CUD) is a growing public health concern, with rising prevalence and significant impact on individuals across age groups. This systematic review examines 24 studies investigating pharmacological and non-pharmacological interventions for CUD among adolescents (up to 17), young adults (18–24), and older adults (25–65). Database searches were conducted for randomized controlled trials of CUD interventions reporting outcomes such as cannabis use, abstinence, withdrawal symptoms, and treatment retention. For adolescents, interventions such as contingent rewards and family engagement have shown promise, while young adults benefit from technology-based platforms and peer support. In older adults, pharmacological adjuncts combined with counseling have shown promise in enhancing treatment outcomes. However, optimal treatment combinations remain uncertain, highlighting the need for further research. Addressing CUD requires tailored interventions that acknowledge developmental stages and challenges across the lifespan. Although promising interventions exist, further comparative effectiveness research is needed to delineate the most efficacious approaches. Full article

PIEZO1 is a mechanosensitive ion channel expressed in various organs, including but not limited to the brain, heart, lungs, kidneys, bone, and skin. PIEZO1 has been implicated in astrocyte, microglia, capillary, and oligodendrocyte signaling in the mammalian cortex. Using murine embryonic frontal cortex tissue, we examined the protein expression and functionality of PIEZO1 channels in cultured networks leveraging substrate-integrated microelectrode arrays (MEAs) with additional quantitative results from calcium imaging and whole-cell patch-clamp electrophysiology. MEA data show that the PIEZO1 agonist Yoda1 transiently enhances the mean firing rate (MFR) of single units, while the PIEZO1 antagonist GsMTx4 inhibits both spontaneous activity and Yoda1-induced increase in MFR in cortical networks. Furthermore, calcium imaging experiments revealed that Yoda1 significantly increased the frequency of calcium transients in cortical cells. Additionally, in voltage clamp experiments, Yoda1 exposure shifted the cellular reversal potential towards depolarized potentials consistent with the behavior of PIEZO1 as a non-specific cation-permeable channel. Our work demonstrates that murine frontal cortical neurons express functional PIEZO1 channels and quantifies the electrophysiological effects of channel activation in vitro. By quantifying the electrophysiological effects of PIEZO1 activation in vitro, our study establishes a foundation for future investigations into the role of PIEZO1 in neurological processes and potential therapeutic applications targeting mechanosensitive channels in various physiological contexts. Full article

The development of noninvasive and cost-effective methods of detecting Alzheimer’s disease (AD) is essential for its early prevention and mitigation. We optimize the detection of AD using natural language processing (NLP) of spontaneous speech through the use of audio enhancement techniques and novel transcription methodologies. Specifically, we utilized Boll Spectral Subtraction to improve audio fidelity and created transcriptions using state-of-the-art AI services—locally-based Wav2Vec and Whisper, alongside cloud-based IBM Cloud and Rev AI—evaluating their performance against traditional manual transcription methods. Support Vector Machine (SVM) classifiers were then trained and tested using GPT-based embeddings of transcriptions. Our findings revealed that AI-based transcriptions largely outperformed traditional manual ones, with Wav2Vec (enhanced audio) achieving the best accuracy and F-1 score (0.99 for both metrics) for locally-based systems and Rev AI (standard audio) performing the best for cloud-based systems (0.96 for both metrics). Furthermore, this study revealed the detrimental effects of interviewer speech on model performance in addition to the minimal effect of audio enhancement. Based on our findings, current AI transcription and NLP technologies are highly effective at accurately detecting AD with available data but struggle to classify probable AD and mild cognitive impairment (MCI), a prodromal stage of AD, due to a lack of training data, laying the groundwork for the future implementation of an automatic AD detection system. Full article

First-line treatments for post-traumatic stress disorder (PTSD) encompass a wide range of pharmacotherapies and psychotherapies. However, many patients fail to respond to such interventions, highlighting the need for novel approaches. Due to its ability to modulate cortical activity, non-invasive brain stimulation (NIBS) could represent a valuable therapeutic tool. Therefore, the aim of this systematic review is to summarize and discuss the existing evidence on the ameliorative effects of NIBS on PTSD and comorbid anxiety and depressive symptoms. Our goal is also to debate the effectiveness of an integrated approach characterized by the combination of NIBS and psychotherapy. This search was conducted following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines in the PubMed, PsycINFO, PsycARTICLES, PSYINDEX, MEDLINE, and ERIC databases. Overall, 31 studies met the eligibility criteria, yielding a total of 26 clinical trials employing transcranial magnetic stimulation (TMS) and 5 making use of transcranial direct-current stimulation (tDCS). From these studies, it emerged that NIBS consistently reduced overall PTSD symptoms’ severity as well as comorbid anxiety and depressive symptoms. Moreover, we speculate that combining NIBS with prolonged exposure or cognitive processing therapy might represent a promising therapeutic approach for consistently ameliorating subjects’ clinical conditions. Full article

The gut–brain axis (GBA) plays a significant role in various neurodegenerative disorders, such as Alzheimer’s disease (AD), and the gut microbiome (GM) can bidirectionally communicate with the brain through the GBA. Thus, recent evidence indicates that the GM may affect the pathological features and the progression of AD in humans. The aim of our study was to elucidate the impact of probiotics on the pathological features of AD in a 5xFAD model. Probiotics (Bifidobacterium lactis, Levilactobacillus brevis, and Limosilactobacillus fermentum) were orally administered in 5xFAD mice to modify the GM composition. Additionally, freeze-dried food containing phosphatidylserine was used as the positive control. Behavioral pathogenesis was assessed through the cross maze and Morris water maze tests. Our findings revealed that probiotic administration resulted in significant improvements in spatial and recognition memories. Furthermore, the neuroprotective effects of probiotics were substantiated by a reduction in amyloid-β accumulation in critical brain regions. Microglial activation in 5xFAD mice was also attenuated by probiotics in the hippocampus and cerebral cortex. Moreover, elevated tau phosphorylation in 5xFAD mice was ameliorated in the probiotics-treated group. The results highlight the potential use of probiotics as a neuroprotective intervention in AD. Full article

Quick decision making is a vital factor for a successful pass in soccer games. Many previous studies of decision making in soccer focused on motor execution, but inhibitory processing has remained unclear. This study aimed to clarify the differences in motor execution and inhibitory among Japanese collegiate soccer players with different skill levels. We evaluated the behavioral data and event-related potentials in the high-skilled, low-skilled, and novice groups during the Go/No-go and pass choice reaction tasks. The reaction time (RT) was significantly shorter in the high group than in the novice group, and RT variability was small in the high group. The amplitude of the N2 component was significantly larger in the high group than in the low and novice groups, and the latency of the P3 component was significantly shorter in the high and low groups than in the novice group during the pass choice reaction task. The subtracted No-go N2 amplitude was also significantly larger in the high and low groups than in the novice group, and correlations existed between the RT, RT variability, and the subtracted No-go N2 amplitude during these tasks. These data indicate that soccer players’ behavioral responses and inhibition processing decision-making activities are associated with skill levels. Full article

Eating disorders are a group of psychiatric conditions that involve pathological relationships between patients and food. The most prolific of these disorders are anorexia nervosa, bulimia nervosa, and binge eating disorder. The current standard of care involves psychotherapy, pharmacotherapy, and the management of comorbid conditions, with nutritional rehabilitation reserved for severe cases of anorexia nervosa. Unfortunately, many patients often fail to respond, leaving a concerning treatment gap between the current and requisite treatments for eating disorders. To better understand the neurobiology underlying these eating disorders, investigations have been undertaken to characterize the activity of various neural networks, primarily those activated during tasks of executive inhibition, reward processing, and self-reference. Various neuromodulatory techniques have been proposed to stimulate these networks with the goal of improving patients’ BMI and mental health. The aim of this review is to compile a comprehensive summarization of the current literature regarding the underlying neural connectivity of anorexia nervosa, bulimia nervosa, and binge eating disorder as well as the numerous neuromodulatory modalities that have been investigated. Importantly, we aimed to summarize the most significant clinical trials to date as well as to provide an updated assessment of the role of deep brain stimulation, summarizing numerous recently published clinical studies that have greatly contributed to the literature. In this review, we found therapeutic evidence for transcranial magnetic stimulation and transcranial direct current stimulation in treating individuals suffering from anorexia nervosa, bulimia nervosa, and binge eating disorder. We also found significant evidence for the role of deep brain stimulation, particularly as an escalatory therapy option for the those who failed standard therapy. Finally, we hope to provide promising directions for future clinical investigations. Full article

Introduction: Exercise therapy may increase brain-derived neurotrophic factor (BDNF) levels and improve clinical outcomes in people living with Parkinson’s disease (PD). This systematic review was performed to investigate the effect of exercise therapy on BDNF levels and clinical outcomes in human PD and to discuss mechanisms proposed by authors. Method: A search on the literature was performed on PubMed up to December 2023 using the following key words: Parkinson’s disease AND exercise, exercise therapy, neurological rehabilitation AND brain-derived neurotrophic factor, brain-derived neurotrophic factor/blood, brain-derived neurotrophic factor/cerebrospinal fluid AND randomized clinical trial, intervention study. Only randomized clinical trials comparing an exercise intervention to treatment as usual, usual care (UC), sham intervention, or no intervention were included. Results: A meta-analysis of BDNF outcomes with pooled data from five trials (N = 216 participants) resulted in a significant standardized mean difference (SMD) of 1.20 [95% CI 0.53 to 1.87; Z = 3.52, p = 0.0004, I² = 77%], favoring exercise using motorized treadmill, Speedflex machine, rowing machine, and non-specified exercise. Significant improvements were found in Unified Parkinson’s Disease Rating Scale (UPDRS), UPDRS-III, 6 Minute Walk Test (6MWT), and Berg Balance Scale (BBS). Methodological quality of trials was categorized as “good” in three trials, “fair” in one trial, and “poor” in one trial. Conclusion: Key results of this systematic review are that exercise therapy is effective in raising serum BDNF levels and seems effective in alleviating PD motor symptoms. Exercise therapy confers neuroplastic effects on Parkinson brain, mediated, in part, by BDNF. Full article

Brain-Computer Interfaces (BCIs) aim to establish a pathway between the brain and an external device without the involvement of the motor system, relying exclusively on neural signals. Such systems have the potential to provide a means of communication for patients who have lost the ability to speak due to a neurological disorder. Traditional methodologies for decoding imagined speech directly from brain signals often deploy static classifiers, that is, decoders that are computed once at the beginning of the experiment and remain unchanged throughout the BCI use. However, this approach might be inadequate to effectively handle the non-stationary nature of electroencephalography (EEG) signals and the learning that accompanies BCI use, as parameters are expected to change, and all the more in a real-time setting. To address this limitation, we developed an adaptive classifier that updates its parameters based on the incoming data in real time. We first identified optimal parameters (the update coefficient, UC) to be used in an adaptive Linear Discriminant Analysis (LDA) classifier, using a previously recorded EEG dataset, acquired while healthy participants controlled a binary BCI based on imagined syllable decoding. We subsequently tested the effectiveness of this optimization in a real-time BCI control setting. Twenty healthy participants performed two BCI control sessions based on the imagery of two syllables, using a static LDA and an adaptive LDA classifier, in randomized order. As hypothesized, the adaptive classifier led to better performances than the static one in this real-time BCI control task. Furthermore, the optimal parameters for the adaptive classifier were closely aligned in both datasets, acquired using the same syllable imagery task. These findings highlight the effectiveness and reliability of adaptive LDA classifiers for real-time imagined speech decoding. Such an improvement can shorten the training time and favor the development of multi-class BCIs, representing a clear interest for non-invasive systems notably characterized by low decoding accuracies. Full article

Background: Vestibular migraine (VM) is common migraine that occurs in patients with dizziness. Vestibular rehabilitation for managing VM generally remains unclear. Recently, it has been reported that transcranial direct current stimulation (tDCS) has positive effects in alleviating dizziness. This study investigated the effects of tDCS on dizziness and cortical activation in a patient with VM. Methods: We recruited a male patient aged 31 years with no dizziness. The patient watched a video to induce dizziness using a virtual reality device. The study applied the intervention using tDCS for 4 weeks and measured 4 assessments: functional near-infrared spectroscopy (fNIRS), quantitative electroencephalography (qEEG), dizziness handicap inventory, and visual vertigo analog scale. Results: We showed the activation in the middle temporal gyrus and inferior temporal gyrus (ITG) of the left hemisphere and in the superior temporal gyrus and ITG of the right hemisphere in the pre-intervention. After the intervention, the activation of these areas decreased. In the results of qEEG, excessive activation of C3, P3, and T5 in the left hemisphere and C4 in the right hemisphere before intervention disappeared after the intervention. Conclusions: This study indicated that tDCS-based intervention could be considered a viable approach to treating patients with vestibular dysfunction and dizziness caused by VM. Full article

Amyotrophic lateral sclerosis (ALS) involves the degeneration of motor neurons and debilitating and possibly fatal symptoms. The COVID-19 pandemic directly affected the quality of life of this group, and the SARS-CoV-2 infection accelerated the present neuroinflammatory process. Furthermore, studies indicate that the infection may have led to the development of the pathology. Thus, the scenario after this pandemic presents “long-lasting COVID” as a disease that affects people who have been infected. From this perspective, studying the pathophysiology behind ALS associated with SARS-CoV-2 infection and possible supporting therapies becomes necessary when we understand the impact on the quality of life of these patients. Thus, the purinergic system was trained to demonstrate how its modulation can add to the treatment, reduce disease progression, and result in better prognoses. From our studies, we highlight the P2X7, P2X4, and A2AR receptors and how their activity can directly influence the ALS pathway. Full article

Recently, a recurrent de novo dominant mutation in UBTF (c.628G>A, p.Glu210Lys; UBTF E210K) was identified as the cause of a neurological disorder which has been named UBTF Neuroregression Syndrome (UNS), or Childhood-Onset Neurodegeneration with Brain Atrophy (CONDBA). To date, only 17 cases have been reported worldwide. The molecular etiology is a pathogenic variant, E210K, within the HMG-box 2 of Upstream Binding Transcription Factor (UBTF). UBTF, a nucleolar protein, plays an important role in ribosomal RNA (rRNA) synthesis, nucleolar integrity, and cell survival. This variant causes unstable preinitiation complexes to form, resulting in altered rDNA chromatin structures, rRNA dysregulation, DNA damage, and ultimately, neurodegeneration. Defining clinical characteristics of the disorder include but are not limited to developmental regression beginning at approximately three years of age, progressive motor dysfunction, declining cognition, ambulatory loss, and behavioral problems. Histological and neuroimaging abnormalities include cortical atrophy, white matter deficits, and enlarged ventricles. Herein, we present a detailed overview of all published cases as well as the functional roles of UBTF to better understand the pathophysiology. Bringing undiagnosed cases to the attention of clinicians and researchers by making them aware of the clinical features will improve research and support the development of therapeutic interventions. Full article

Complex motor skills can be acquired while observing a model without physical practice. Transcranial direct-current stimulation (tDCS) applied to the primary motor cortex (M1) also facilitates motor learning. However, the effectiveness of observational practice for bimanual coordination skills is debated. We compared the behavioural and brain causal connectivity patterns following three interventions: primary motor cortex stimulation (M1-tDCS), action-observation (AO) and a combined group (AO+M1-tDCS) when acquiring a bimanual, two-ball juggling skill. Thirty healthy young adults with no juggling experience were randomly assigned to either video observation of a skilled juggler, anodal M1-tDCS or video observation combined with M1-tDCS. Thirty trials of juggling were performed and scored after the intervention. Resting-state EEG data were collected before and after the intervention. Information flow rate was applied to EEG source data to measure causal connectivity. The two observation groups were more accurate than the tDCS alone group. In the AO condition, there was strong information exchange from (L) parietal to (R) parietal regions, strong bidirectional information exchange between (R) parietal and (R) occipital regions and an extensive network of activity that was (L) lateralized. The M1-tDCS condition was characterized by bilateral long-range connections with the strongest information exchange from the (R) occipital region to the (R) temporal and (L) occipital regions. AO+M1-tDCS induced strong bidirectional information exchange in occipital and temporal regions in both hemispheres. Uniquely, it was the only condition that was characterized by information exchange between the (R) frontal and central regions. This study provides new results about the distinct network dynamics of stimulating the brain for skill acquisition, providing insights for motor rehabilitation. Full article

Drug-resistant epilepsy (DRE) is often treated with surgery or neuromodulation. Specifically, responsive neurostimulation (RNS) is a widely used therapy that is programmed to detect abnormal brain activity and intervene with tailored stimulation. Despite the success of RNS, some patients require further interventions. However, having an RNS device in situ is a hindrance to the performance of neuroimaging techniques. Magnetoencephalography (MEG), a non-invasive neurophysiologic and functional imaging technique, aids epilepsy assessment and surgery planning. MEG performed post-RNS is complicated by signal distortions. This study proposes an independent component analysis (ICA)-based approach to enhance MEG signal quality, facilitating improved assessment for epilepsy patients with implanted RNS devices. Three epilepsy patients, two with RNS implants and one without, underwent MEG scans. Preprocessing included temporal signal space separation (tSSS) and an automated ICA-based approach with MNE-Python. Power spectral density (PSD) and signal-to-noise ratio (SNR) were analyzed, and MEG dipole analysis was conducted using single equivalent current dipole (SECD) modeling. The ICA-based noise removal preprocessing method substantially improved the signal-to-noise ratio (SNR) for MEG data from epilepsy patients with implanted RNS devices. Qualitative assessment confirmed enhanced signal readability and improved MEG dipole analysis. ICA-based processing markedly enhanced MEG data quality in RNS patients, emphasizing its clinical relevance. Full article

Social communication skills, especially eye contact and joint attention, are frequently impaired in autism spectrum disorder (ASD) and predict functional outcomes. Applied behavior analysis is one of the most common evidence-based treatments for ASD, but it is not accessible to most families in low- and middle-income countries (LMICs) as it is an expensive and intensive treatment and needs to be delivered by highly specialized professionals. Parental training has emerged as an effective alternative. This is an exploratory study to assess a parental intervention group via video modeling to acquire eye contact and joint attention. Four graded measures of eye contact and joint attention (full physical prompt, partial physical prompt, gestural prompt, and independent) were assessed in 34 children with ASD and intellectual disability (ID). There was a progressive reduction in the level of prompting required over time to acquire eye contact and joint attention, as well as a positive correlation between the time of exposure to the intervention and the acquisition of abilities. This kind of parent training using video modeling to teach eye contact and joint attention skills to children with ASD and ID is a low-cost intervention that can be applied in low-resource settings. Full article

Crowding occurs when an easily identified isolated stimulus is surrounded by stimuli with similar properties, making it very difficult to identify. Crowding is suggested as a mechanism that creates a bottleneck in object recognition and awareness. Recently, we showed that brief presentation times at the fovea resulted in a significant crowding effect on target identification, impaired the target’s color awareness, and resulted in a slower reaction time. However, when tagging the target with a red letter, the crowding effect is abolished. Crowding is widely considered a grouping; hence, it is pre-attentive. An event-related potential (ERP) study that investigated the spatial–temporal properties of crowding suggested the involvement of higher-level visual processing. Here, we investigated whether ERP’s components may be affected by crowding and tagging, and whether the temporal advantage of ERP can be utilized to gain further information about the crowding mechanism. The participants reported target identification using our standard foveal crowing paradigm. It is assumed that crowding occurs due to a suppressive effect; thus, it can be probed by changes in perceptual (N1, ~160 ms) and attentive (P3 ~300–400 ms) components. We found a suppression effect (less negative ERP magnitude) in N1 under foveal crowding, which was recovered under tagging conditions. ERP’s amplitude components (N1 and P3) and the behavioral proportion correct are highly correlated. These findings suggest that crowding is an early grouping mechanism that may be combined with later processing involving the segmentation mechanism. Full article

Human language and social cognition are two key disciplines that have traditionally been studied as separate domains. Nonetheless, an emerging view suggests an alternative perspective. Drawing on the theoretical underpinnings of the social brain hypothesis (thesis of the evolution of brain size and intelligence), the social complexity hypothesis (thesis of the evolution of communication), and empirical research from comparative animal behavior, human social behavior, language acquisition in children, social cognitive neuroscience, and the cognitive neuroscience of language, it is argued that social cognition and language are two significantly interconnected capacities of the human species. Here, evidence in support of this view reviews (1) recent developmental studies on language learning in infants and young children, pointing to the important crucial benefits associated with social stimulation for youngsters, including the quality and quantity of incoming linguistic information, dyadic infant/child-to-parent non-verbal and verbal interactions, and other important social cues integral for facilitating language learning and social bonding; (2) studies of the adult human brain, suggesting a high degree of specialization for sociolinguistic information processing, memory retrieval, and comprehension, suggesting that the function of these neural areas may connect social cognition with language and social bonding; (3) developmental deficits in language and social cognition, including autism spectrum disorder (ASD), illustrating a unique developmental profile, further linking language, social cognition, and social bonding; and (4) neural biomarkers that may help to identify early developmental disorders of language and social cognition. In effect, the social brain and social complexity hypotheses may jointly help to describe how neurotypical children and adults acquire language, why autistic children and adults exhibit simultaneous deficits in language and social cognition, and why nonhuman primates and other organisms with significant computational capacities cannot learn language. But perhaps most critically, the following article argues that this and related research will allow scientists to generate a holistic profile and deeper understanding of the healthy adult social brain while developing more innovative and effective diagnoses, prognoses, and treatments for maladies and deficits also associated with the social brain. Full article

Astrocytes displaying reactive phenotypes are characterized by their ability to remodel morphologically, molecularly, and functionally in response to pathological stimuli. This process results in the loss of their typical astrocyte functions and the acquisition of neurotoxic or neuroprotective roles. A growing body of research indicates that these reactive astrocytes play a pivotal role in the pathogenesis of amyotrophic lateral sclerosis (ALS), involving calcium homeostasis imbalance, mitochondrial dysfunction, abnormal lipid and lactate metabolism, glutamate excitotoxicity, etc. This review summarizes the characteristics of reactive astrocytes, their role in the pathogenesis of ALS, and recent advancements in astrocyte-targeting strategies. Full article

Despite recent efforts to search for biomarkers for the pre-symptomatic diagnosis of Parkinson’s disease (PD), the presence of risk factors, prodromal signs, and family history still support the classification of individuals at risk for this disease. Human epidemiological studies are useful in this search but fail to provide causality. The study of well-known risk factors for PD in animal models can help elucidate mechanisms related to the disease’s etiology and contribute to future prevention or treatment approaches. This narrative review aims to discuss animal studies that investigated four of the main risk factors and/or prodromal signs related to PD: advanced age, male sex, sleep alterations, and depression. Different databases were used to search the studies, which were included based on their relevance to the topic. Although still in a reduced number, such studies are of great relevance in the search for evidence that leads to a possible early diagnosis and improvements in methods of prevention and treatment. Full article

Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) have been related to an increased risk for behavioral addictions including online gaming. However, the relationship between these two conditions and Internet gaming disorder (IGD) is still debated. The aim of this study is to address this topic by exploring the prevalence of IGD in a consecutive sample of ASD youth and ADHD youth, compared with a normal control group, and by assessing selected psychopathological and neuropsychological features in ASD and ADHD patients with and without IGD. This study included 77 ASD patients (67 males, mean age 13.58 ± 2.75 years), 94 ADHD patients (79 males, mean age 11.46 ± 2.47 years), and 147 normal controls (NC) (mean age 13.9 ± 3.0 years, 114 males) that received structured measures for IGD (IAT, IGDS9-SF, and UADI). In the ADHD group, 72.34% of the sample were above the IGD cut-off, compared with 45.45% in the ASD group and 9.5% in the NC group. ASD patients with IGD presented with greater severity and more severe attention problems, with no difference in the ASD core symptoms between patients with and without IGD. In the comparison between the ASD and ADHD groups according to the presence of IGD, ASD patients with IGD were the most severe group according to the CGI (Clinical Global Impression) scale. The follow-up, conducted on 45 patients affected by ASD, showed an improvement in CGI and CGAS (Children’s Global Assessment Scale) scores, but not in the IGD symptoms. These findings could place the diagnosis of ASD as a negative prognostic factor in the follow-up of aspects of video game addiction compared with ADHD. Full article

Animal models have been used to gain pathophysiologic insights into Parkinson’s disease (PD) and aid in the translational efforts of interventions with therapeutic potential in human clinical trials. However, no disease-modifying therapy for PD has successfully emerged from model predictions. These translational disappointments warrant a reappraisal of the types of preclinical questions asked of animal models. Besides the limitations of experimental designs, the one-size convergence and oversimplification yielded by a model cannot recapitulate the molecular diversity within and between PD patients. Here, we compare the strengths and pitfalls of different models, review the discrepancies between animal and human data on similar pathologic and molecular mechanisms, assess the potential of organoids as novel modeling tools, and evaluate the types of questions for which models can guide and misguide. We propose that animal models may be of greatest utility in the evaluation of molecular mechanisms, neural pathways, drug toxicity, and safety but can be unreliable or misleading when used to generate pathophysiologic hypotheses or predict therapeutic efficacy for compounds with potential neuroprotective effects in humans. To enhance the translational disease-modification potential, the modeling must reflect the biology not of a diseased population but of subtypes of diseased humans to distinguish What data are relevant and to Whom. Full article

While the term task load (TL) refers to external task demands, the amount of work, or the number of tasks to be performed, mental workload (MWL) refers to the individual’s effort, mental capacity, or cognitive resources utilized while performing a task. MWL in multitasking scenarios is often closely linked with the quantity of tasks a person is handling within a given timeframe. In this study, we challenge this hypothesis from the perspective of electroencephalography (EEG) using a deep learning approach. We conducted an EEG experiment with 50 participants performing NASA Multi-Attribute Task Battery II (MATB-II) under 4 different task load levels. We designed a convolutional neural network (CNN) to help with two distinct classification tasks. In one setting, the CNN was used to classify EEG segments based on their task load level. In another setting, the same CNN architecture was trained again to detect the presence of individual MATB-II subtasks. Results show that, while the model successfully learns to detect whether a particular subtask is active in a given segment (i.e., to differentiate between different subtasks-related EEG patterns), it struggles to differentiate between the two highest levels of task load (i.e., to distinguish MWL-related EEG patterns). We speculate that the challenge comes from two factors: first, the experiment was designed in a way that these two highest levels differed only in the quantity of work within a given timeframe; and second, the participants’ effective adaptation to increased task demands, as evidenced by low error rates. Consequently, this indicates that under such conditions in multitasking, EEG may not reflect distinct enough patterns to differentiate higher levels of task load. Full article

While extensive research has documented the cognitive changes associated with Parkinson’s disease (PD), a relatively small portion of the empirical literature investigated the language abilities of individuals with PD. Recently, artificial intelligence applied to linguistic data has shown promising results in predicting the clinical diagnosis of neurodegenerative disorders, but a deeper investigation of the current literature available on PD is lacking. This systematic review investigates the nature of language disorders in PD by assessing the contribution of machine learning (ML) to the classification of patients with PD. A total of 10 studies published between 2016 and 2023 were included in this review. Tasks used to elicit language were mainly structured or unstructured narrative discourse. Transcriptions were mostly analyzed using Natural Language Processing (NLP) techniques. The classification accuracy (%) ranged from 43 to 94, sensitivity (%) ranged from 8 to 95, specificity (%) ranged from 3 to 100, AUC (%) ranged from 32 to 97. The most frequent optimal linguistic measures were lexico-semantic (40%), followed by NLP-extracted features (26%) and morphological consistency features (20%). Artificial intelligence applied to linguistic markers provides valuable insights into PD. However, analyzing measures derived from narrative discourse can be time-consuming, and utilizing ML requires specialized expertise. Moving forward, it is important to focus on facilitating the integration of both narrative discourse analysis and artificial intelligence into clinical practice. Full article

Brain spaces around (perivascular spaces) and alongside (paravascular or Virchow–Robin spaces) vessels have gained significant attention in recent years due to the advancements of in vivo imaging tools and to their crucial role in maintaining brain health, contributing to the anatomic foundation of the glymphatic system. In fact, it is widely accepted that peri- and para-vascular spaces function as waste clearance pathways for the brain for materials such as ß-amyloid by allowing exchange between cerebrospinal fluid and interstitial fluid. Visible brain spaces on magnetic resonance imaging are often a normal finding, but they have also been associated with a wide range of neurological and systemic conditions, suggesting their potential as early indicators of intracranial pressure and neurofluid imbalance. Nonetheless, several aspects of these spaces are still controversial. This article offers an overview of the current knowledge and magnetic resonance imaging characteristics of peri- and para-vascular spaces, which can help in daily clinical practice image description and interpretation. This paper is organized into different sections, including the microscopic anatomy of peri- and para-vascular spaces, their associations with pathological and physiological events, and their differential diagnosis. Full article

Developmental dyslexia (DD) is a learning disorder. Although risk genes have been identified, environmental factors, and particularly stress arising from constant difficulties, have been associated with the occurrence of DD by affecting brain plasticity and function, especially during critical neurodevelopmental stages. In this work, electroencephalogram (EEG) findings were coupled with the genetic and epigenetic molecular signatures of individuals with DD and matched controls. Specifically, we investigated the genetic and epigenetic correlates of key stress-associated genes (NR3C1, NR3C2, FKBP5, GILZ, SLC6A4) with psychological characteristics (depression, anxiety, and stress) often included in DD diagnostic criteria, as well as with brain EEG findings. We paired the observed brain rhythms with the expression levels of stress-related genes, investigated the epigenetic profile of the stress regulator glucocorticoid receptor (GR) and correlated such indices with demographic findings. This study presents a new interdisciplinary approach and findings that support the idea that stress, attributed to the demands of the school environment, may act as a contributing factor in the occurrence of the DD phenotype. Full article

Spinal cord injury (SCI) consists of damage to any segment of the spinal cord extending to potential harm to nerves in the cauda equina. Rehabilitative efforts for SCI can involve conventional physiotherapy, innovative technologies, as well as cognitive treatment and psychological support. The aim of this study is to evaluate the feasibility of a dedicated, multidisciplinary, and integrated intervention path for SCI, encompassing both conventional and technological interventions, while observing their impact on cognitive, motor, and behavioral outcomes and the overall quality of life for individuals with SCI. Forty-two patients with SCI were included in the analysis utilizing electronic recovery system data. The treatment regimen included multidisciplinary rehabilitation approaches, such as traditional physiotherapy sessions, speech therapy, psychological support, robotic devices, advanced cognitive rehabilitation, and other interventions. Pre–post comparisons showed a significant improvement in lower limb function (Fugl Meyer Assessment-FMA < 0.001), global cognitive functioning (Montreal Cognitive Assessment-MoCA p < 0.001), and perceived quality of life at both a physical and mental level (Short Form-12-SF-12 p < 0.001). Furthermore, we found a significant reduction in depressive state (Beck Depression Inventory-BDI p < 0.001). In addition, we assessed patient satisfaction using the Short Form of the Patient Satisfaction Questionnaire (PSQ), offering insights into the subjective evaluation of the intervention. In conclusion, this retrospective study provides positive results in terms of improvements in motor function, cognitive functions, and quality of life, highlighting the importance of exploring multidisciplinary approaches. Full article

Introduction: Down syndrome (DS) stands out as one of the most prevalent genetic disorders, imposing a significant burden on both society and the healthcare system. Scientists are making efforts to understand the neural mechanisms behind the pathophysiology of this disorder. Among the valuable methods for studying these mechanisms is electroencephalography (EEG), a non-invasive technique that measures the brain’s electrical activity, characterised by its excellent temporal resolution. This review aims to consolidate studies examining EEG usage in individuals with DS. The objective was to identify shared elements of disrupted EEG activity and, crucially, to elucidate the neural mechanisms underpinning these deviations. Searches were conducted on Pubmed/Medline, Research Gate, and Cochrane databases. Results: The literature search yielded 17 relevant articles. Despite the significant time span, small sample size, and overall heterogeneity of the included studies, three common features of aberrant EEG activity in people with DS were found. Potential mechanisms for this altered activity were delineated. Conclusions: The studies included in this review show altered EEG activity in people with DS compared to the control group. To bolster these current findings, future investigations with larger sample sizes are imperative. Full article

Irrational beliefs of Demandingness, Catastrophizing, Low Frustration Tolerance, and Depreciation have demonstrated prevalence in disparate areas of life, including psychopathology, the military, politics, religion, and education. Individuals with mental health concerns, such as Post-Traumatic Stress Disorder (PTSD), endorse elevations in such thoughts compared to the general population. This commentary describes the rationale for focusing on irrational beliefs in efforts to address PTSD and presents the Rational Emotive Behavior Therapy (REBT)-Informed Group for PTSD as a potential novel application of a well-established intervention. In support of these suggestions, we present a narrative review of the published work on irrational beliefs and REBT tenets as relevant for PTSD. We then introduce and describe the REBT-Informed Group intervention, summarize the prior preliminary research conducted by our group, and present some novel data from a re-analysis of this prior work. We end with commentary related to future directions of REBT approaches for PTSD to address limitations and expand the impact of the treatment to military and other Veteran or civilian populations. Full article

Explored through EEG/MEG, auditory stimuli function as a suitable research probe to reveal various neural activities, including event-related potentials, brain oscillations and functional connectivity. Accumulating evidence in this field stems from studies investigating neuroplasticity induced by long-term auditory training, specifically cross-sectional studies comparing musicians and non-musicians as well as longitudinal studies with musicians. In contrast, studies that address the neural effects of short-term interventions whose duration lasts from minutes to hours are only beginning to be featured. Over the past decade, an increasing body of evidence has shown that short-term auditory interventions evoke rapid changes in neural activities, and oscillatory fluctuations can be observed even in the prestimulus period. In this scoping review, we divided the extracted neurophysiological studies into three groups to discuss neural activities with short-term auditory interventions: the pre-stimulus period, during stimulation, and a comparison of before and after stimulation. We show that oscillatory activities vary depending on the context of the stimuli and are greatly affected by the interplay of bottom-up and top-down modulational mechanisms, including attention. We conclude that the observed rapid changes in neural activitiesin the auditory cortex and the higher-order cognitive part of the brain are causally attributed to short-term auditory interventions. Full article

Children with developmental dyslexia (DD) often struggle with executive function difficulties which can continue into adulthood if not addressed. This double-blinded randomized clinical trial study evaluated the short-term effects of the Verbal Working Memory-Balance (VWM-B) program on reading-related executive functions, reading skills, and reading comprehension in Persian children with DD. The active control group [12 children with DD with a mean age of 9 years (SD = 0.90)] received training using the single-task VWM program, while the experiment group [15 children with DD with a mean age of 8 years (SD = 0.74)] received training with the dual-task VWM-B program. Both groups received fifteen training sessions, and assessments were conducted before and after the intervention. The groups were homogenized for possible confounders of age, gender, IQ level, and attention level. The study employed separate mixed ANOVA analyses to estimate the impact of training programs on various measured functions. Significant improvements were observed in the outcome measures of backward digit span, text comprehension, verbal fluency, Stroop color–word test and interference, and the reading subtests. Additionally, significant correlations were found between reading skills and backward digit span, text comprehension, verbal fluency, and Stroop variables. In conclusion, the dual-task VWM-B program was found to be more effective than the single-task VWM program in improving selective attention, cognitive inhibition, verbal working memory capacity, information processing speed, naming ability, and lexical access speed. These enhanced executive functions were associated with improved reading skills in children with DD. Full article

People with obsessive compulsive disorder (OCD) are at increased risk of developing psychotic disorders; yet little is known about specific clinical features which might hint at this vulnerability. The present study was aimed at elucidating the pathophysiological mechanism linking OCD to psychosis through the investigation of childhood trauma experiences in adolescents and adults with OCD. One hundred outpatients, aged between 12 and 65 years old, were administered the Yale–Brown Obsessive Compulsive Scale (Y-BOCS) and its Child version (CY-BOCS), as well as the Childhood Trauma Questionnaire (CTQ); Cognitive–Perceptual basic symptoms (COPER) and high-risk criterion Cognitive Disturbances (COGDIS) were assessed in the study sample. Greater childhood trauma experiences were found to predict psychotic vulnerability (p = 0.018), as well as more severe OCD symptoms (p = 0.010) and an earlier age of OCD onset (p = 0.050). Participants with psychotic vulnerability reported higher scores on childhood trauma experiences (p = 0.02), specifically in the emotional neglect domain (p = 0.01). In turn, emotional neglect and psychotic vulnerability were found higher in the pediatric group than in the adult group (p = 0.01). Our findings suggest that childhood trauma in people with OCD may represent an indicator of psychotic vulnerability, especially in those with an earlier OCD onset. Research on the pathogenic pathways linking trauma, OCD, and psychosis is needed. Full article

This comprehensive review delves into the cognitive neuroscience of hypnosis and variations in hypnotizability by examining research employing functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and electroencephalography (EEG) methods. Key focus areas include functional brain imaging correlations in hypnosis, EEG band oscillations as indicators of hypnotic states, alterations in EEG functional connectivity during hypnosis and wakefulness, drawing critical conclusions, and suggesting future research directions. The reviewed functional connectivity findings support the notion that disruptions in the available integration between different components of the executive control network during hypnosis may correspond to altered subjective appraisals of the agency during the hypnotic response, as per dissociated and cold control theories of hypnosis. A promising exploration avenue involves investigating how frontal lobes’ neurochemical and aperiodic components of the EEG activity at waking-rest are linked to individual differences in hypnotizability. Future studies investigating the effects of hypnosis on brain function should prioritize examining distinctive activation patterns across various neural networks. Full article