Brain Sci., Volume 13, Issue 12 (December 2023) – 121 articles

Emotional dysregulation (ED) has recently been conceptualized as a transnosographic entity in major mental disorders, and increasing evidence has suggested association between ED and post-traumatic stress symptoms (PTSS), though the nature of this association is unclear. The aim of the present review was to examine the possible interplay between ED and trauma exposure in the literature, as well as a possible role for the comorbidity of PTSD or PTSS in adolescents and young adults. In particular, we explored whether ED may represent a risk factor for PTSD or, conversely, a consequence of traumatic exposure. This systematic review was conducted according to PRISMA 2020 guidelines in three databases (PubMed, Scopus, and Embase). The 34 studies included showed a wide heterogeneity in terms of the populations selected and outcomes examined. Most studies used the Difficulties in Emotion Regulation Scale (DERS) and examined the relationship between ED, trauma, and psychopathological manifestations after the occurrence of trauma, with a focus on child abuse. Although current data in the literature are heterogeneous and inconclusive, this research highlights the role of ED as a mechanism that may mediate vulnerability to PTSD, but also as a predictor of severity and maintenance of typical, atypical, or associated PTSD symptoms, suggesting prevention programs for PTSD and other mental disorders should support the development of emotion regulation strategies. Full article

Intervention parameters such as the challenge, amount, and dosage (challenge × amount) have the potential to alter the efficacy of rehabilitation interventions after stroke. This systematic review investigated the effect of intervention parameters of challenge, amount, and dosage on improvements in walking outcomes following treadmill training (TT) and comparison interventions in people with stroke. Randomized controlled trials were included if they: (i) investigated interventions of TT or bodyweight-supported TT (BWSTT); (ii) made comparisons with other physiotherapy interventions, other types of TT, or no intervention; (iii) studied people with stroke; (iv) reported sufficient data on challenge and amount parameters; and (v) measured walking speed or endurance. Completeness of reporting was evaluated using the TIDieR-Rehab checklist and risk of bias was assessed using the revised Cochrane risk-of-bias tool. The review included 26 studies; 15 studies compared TT or BWSTT with other physiotherapy interventions and 11 studies compared different types of TT. Meta-analyses provided evidence with low to moderate certainty that greater differences in challenge and dosage between treadmill and comparison physiotherapy interventions produced greater effects on walking endurance (p < 0.01). However, challenge and dosage did not influence walking speed outcomes. The analysis of intervention amount was limited by the lack of studies that manipulated the amount of intervention. Overall, the findings indicate that, after stroke, some of the efficacy of TT on walking endurance can be explained by the challenge level during training. This supports the implementation of TT at higher challenge levels in stroke rehabilitation practice. Full article

Objective: This was an open-label pilot study to test the feasibility and preliminary efficacy of a wearable digital intervention developed to improve on-task behavior. This was an exploratory study to test for specificity of response on parent- and teacher-reported symptom outcomes in attention and hyperactive/impulsive symptoms, as well as domains of functional impairment, including school behavior and learning and executive function. Method:Participants included 38 children aged 8–12 years with a parent-reported past diagnosis of ADHD. Following baseline ratings from parents (N = 38) and teachers (N = 26), participants wore the device to school for four weeks. Parent and teacher ratings of ADHD symptoms, executive function, and functional impairment were repeated at the end of the four-week intervention period. Results:Statistically significant improvement was seen in the total scores for all parent and nearly all teacher outcomes, with moderate effect size improvements in attention, organization and planning, self-monitoring, school functioning, and teacher-reported academic performance. Conclusions: Preliminary evidence from this open-label pilot study suggests that having a child interact with a wearable device to self-monitor attention is feasible. This exploratory, open-label pilot study found real-world improvement in functional domains, including academic performance. Future research will require a blinded, randomized, controlled trial using an appropriate sham comparator to confirm these findings. Full article

Background: Glioblastoma (GBM) is categorized as a grade IV astrocytoma by the World Health Organization (WHO), representing the most aggressive and prevalent form of glioma. It presents a significant clinical challenge, with limited treatment options and poor prognosis. This systematic review evaluates the efficacy and safety of various nanotherapy approaches for GBM and explores future directions in tumor management. Nanomedicine, which involves nanoparticles in the 1–100 nm range, shows promise in improving drug delivery and targeting tumor cells. Methods: Following PRISMA guidelines, a systematic search of databases including Google Scholar, NCBI PubMed, Cochrane Library, and ClinicalTrials.gov was conducted to identify clinical trials on GBM and nanomedicine. The primary outcome measures were median overall survival, progression-free survival, and quality of life assessed through Karnofsky performance scores. The safety profile was assessed by adverse events. Results: The analysis included 225 GBM patients, divided into primary and recurrent sub-populations. Primary GBM patients had a median overall survival of 6.75 months, while recurrent GBM patients had a median overall survival of 9.7 months. The mean PFS period was 2.3 months and 3.92 months in primary GBM and recurrent GBM patients, respectively. Nanotherapy showed an improvement in quality of life, with KPS scores increasing after treatment in recurrent GBM patients. Adverse events were observed in 14.2% of patients. Notably, Bevacizumab therapy exhibited better survival outcomes but with a higher incidence of adverse events. Conclusions: Nanotherapy offers a modest increase in survival with fewer severe side effects. It shows promise in improving the quality of life, especially in recurrent GBM patients. However, it falls short in terms of overall survival compared to Bevacizumab. The heterogeneous nature of treatment protocols and reporting methods highlights the need for standardized multicenter trials to further evaluate the potential of nanomedicine in GBM management. Full article

Intermittent fasting (IF) and physical exercise (PE) have beneficial psychological and physiological effects, improving memory and anxiety-like behavior. However, the impact of this combination on brain electrophysiological patterns is unknown. We aimed to evaluate the behavior and parameters of a brain excitability-related phenomenon named cortical spreading depression (CSD) in young rats (31–87 days of life) submitted to IF and treadmill PE for eight weeks. Sixty-four male and female Wistar rats aged 24 days were randomized into control, IF, PE, and IF+PE groups. Behavioral tests (open field (OF), object recognition, and elevated plus maze (EPM)) were performed, and the CSD propagation features were recorded. IF caused behavioral responses indicative of anxiety (lower number of entries and time spent in the OF center and EPM open arms). IF also reduced the discrimination index for object recognition memory tests and increased the propagation velocity of CSD. PE rats displayed more entries into the OF center and lowered CSD propagation speed. Data suggest that IF worsens anxiety-like behavior and memory and accelerates CSD in young rats. In contrast, PE reverted the unfavorable effects of IF. The brain effects of IF and PE at younger ages are recommended for study. Full article

Introduction: Outcome measures using telerehabilitation (TR) in the context of post-stroke rehabilitation are an area of emerging research. The current review assesses the literature related to TR for patients requiring post-stroke rehabilitation. The purpose of this study is to survey the outcome measures used in TR studies and to define which parts of the International Organization of Functioning are measured in trials. Methods: TR studies were searched in Cochrane Central Register of Controlled Trials, PubMed, Embase, Scopus, Google Scholar, and Web of Science, The Cochrane Central Register of Controlled Trials (Cochrane Library), the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and the Physiotherapy Evidence Database (PEDro) from 2016 to June 2023. Two reviewers individually assessed the full text. Discrepancies regarding inclusion or exclusion were resolved by an additional reviewer. Results: A total of 24 studies were included in the current review. The findings were synthesized and presented taking into account their implications within clinical practice, areas of investigation, and strategic implementation. Conclusions: The scoping review has recognized a broad range of outcome measures utilized in TR studies, shedding light on gaps in the current literature. Furthermore, this review serves as a valuable resource for researchers and end users (such as clinicians and policymakers), providing insights into the most appropriate outcome measures for TR. There is a lack of studies examining the required follow-up after TR, emphasizing the need for future research in this area. Full article

Counterfactual conditionals posit hypothetical scenarios in which antecedent events contradict reality. This study examined whether and how the processing difficulty of Chinese counterfactual conditionals (yaobushi, equivalent to if it had not been for in English) can be affected by the length of temporal shifts of the events across clauses and the likelihood of the antecedent occurrence. Participants read Chinese counterfactuals that contained either long (e.g., qunian-xianzai [last year-right now]) or short temporal shifts (e.g., zuotian-xianzai [yesterday-right now]) within highly likely (e.g., sign up for school activity) or less likely contexts (e.g., sign up for Arctic scientific research). ERP results revealed a significant N400 interaction between the temporal shift length and antecedent likelihood on the temporal indicators in the consequent and the sentence-ending verbs. Specifically, the less likely events elicited larger negativity than highly likely events with short temporal shifts on the temporal indicator. On the sentence-ending word, the long temporal shift elicited enlarged negativity than the short temporal shift when the antecedent was highly likely. These findings have two key implications regarding the interplay of implied causality and falsity constraints during counterfactual comprehension. First, salient falsity constraints can override effects of causal coherence on processing. Second, greater negativity for unlikely antecedents suggests that counterfactual markers concurrently activate factual and hypothetical representations. Full article

Clinical prediction models for spine surgery applications are on the rise, with an increasing reliance on machine learning (ML) and deep learning (DL). Many of the predicted outcomes are uncommon; therefore, to ensure the models’ effectiveness in clinical practice it is crucial to properly evaluate them. This systematic review aims to identify and evaluate current research-based ML and DL models applied for spine surgery, specifically those predicting binary outcomes with a focus on their evaluation metrics. Overall, 60 papers were included, and the findings were reported according to the PRISMA guidelines. A total of 13 papers focused on lengths of stay (LOS), 12 on readmissions, 12 on non-home discharge, 6 on mortality, and 5 on reoperations. The target outcomes exhibited data imbalances ranging from 0.44% to 42.4%. A total of 59 papers reported the model’s area under the receiver operating characteristic (AUROC), 28 mentioned accuracies, 33 provided sensitivity, 29 discussed specificity, 28 addressed positive predictive value (PPV), 24 included the negative predictive value (NPV), 25 indicated the Brier score with 10 providing a null model Brier, and 8 detailed the F1 score. Additionally, data visualization varied among the included papers. This review discusses the use of appropriate evaluation schemes in ML and identifies several common errors and potential bias sources in the literature. Embracing these recommendations as the field advances may facilitate the integration of reliable and effective ML models in clinical settings. Full article

This meta-analysis investigates auditory steady-state responses (ASSRs) as potential biomarkers of schizophrenia, focusing on previously unexplored clinical populations, frequencies, and variables. We examined 37 studies, encompassing a diverse cohort of 1788 patients with schizophrenia, including 208 patients with first-episode psychosis, 281 at-risk individuals, and 1603 healthy controls. The results indicate moderate reductions in 40 Hz ASSRs in schizophrenia patients, with significantly greater reductions in first-episode psychosis patients and minimal changes in at-risk individuals. These results call into question the expected progression of ASSR alterations across all stages of schizophrenia. The analysis also revealed the sensitivity of ASSR alterations at 40 Hz to various factors, including stimulus type, level of analysis, and attentional focus. In conclusion, our research highlights ASSRs, particularly at 40 Hz, as potential biomarkers of schizophrenia, revealing varied implications across different stages of the disorder. This study enriches our understanding of ASSRs in schizophrenia, highlighting their potential diagnostic and therapeutic relevance, particularly in the early stages of the disease. Full article

Previous research has documented brain plasticity after an anterior cruciate ligament (ACL) tear and suggests that these neural adaptations contribute to poorer motor control. Since both brain hemispheres show adaptations, we hypothesized that reduced dynamic stability occurs not only in the injured, but also the contralateral, uninjured leg. Further, given brain hemispheric specialization’s impact on motor coordination, we hypothesized the need to consider the injury side. A total of 41 female athletes and 18 controls performed single-leg jump-landings. Dynamic postural stability was measured as time-to-stabilization (TTS). We found reduced medio-lateral dynamic stability for the ACL injured leg (p = 0.006) with a similar trend for the contralateral leg (p = 0.050) compared to the control group. However, when distinguishing between injuries to the dominant and non-dominant legs, we found increased medio-lateral TTS only if the injury had occurred on the dominant side where landings on injured (p = 0.006) and contralateral (p = 0.036) legs required increased TTS. Assessments of dynamic stability, e.g., in the context of return-to-sport, should consider the injury side and compare results not only between the injured and the contralateral leg, but also to uninjured controls. Future research should not pool data from the dominant-leg ACL with non-dominant-leg ACL injuries when assessing post-injury motor performance. Full article

Background: The Italian National Institute of Health (Istituto Superiore di Sanità) funded a 30-month project (July 2021–January 2024) to conduct a twin study of the relationships between Positive Mental Health (PMH) and cellular longevity. Only a few previous studies have focused on the biomarkers of aging in relation to psychological well-being, and none of them exploited the potential of the twin design. Method: In this project, following the standard procedures of the Italian Twin Registry (ITR), we aim to recruit 200 adult twin pairs enrolled in the ITR. They are requested to complete a self-report questionnaire battery on PMH and to undergo a blood withdrawal for the assessment of aging biomarkers, i.e., telomere length and mitochondrial DNA functionality. The association between psychological and aging biomarker measures will be assessed, controlling for genetic and familial confounding effects using the twin study design. Results and conclusions: Biomarker assays are underway. Once data are available for the total study sample, statistical analyses will be performed. The project’s results may shed light on new mechanisms underlying the mind–body connection and may prove helpful to promote psychological well-being in conjunction with biological functioning. Full article

Alzheimer’s disease is prevalent in persons with Down syndrome (DS) as early as their 30s and presents as decreased social interaction, coordination, and physical activity. Therefore, changing attitudes and beliefs about exercise is key to increasing motivation for physical activity especially in middle-age adults with DS. The aim of this study was to examine the effects of Assisted Cycle Therapy (ACT) on self-efficacy and exercise perception in middle-age adults with Down syndrome (DS) following an exercise intervention three times a week for 8 weeks. Twelve participants were in the ACT group in which a motor assisted their cycling to be performed at least 30% faster than voluntary cycling (VC), 10 participants were in the voluntary cycling group, and two participants were in the no cycling (NC) group. The results showed that both exercise groups (i.e., ACT and VC) improved in their self-efficacy after the 8-week intervention. In addition, exercise perception improved following ACT, but not VC or NC. Our results are discussed with respect to their future implications for exercise in the DS population. The results can be attributed to differences in effort required by each intervention group as well as the neurotrophic factors that occur when muscle contractions create synaptic connections resulting in improvement in cognition and feelings of satisfaction. Full article

Headache is a leading cause of disability and suffering. One major challenge in developing device treatments is demonstrating their efficacy given devices’ often-high placebo rate. This paper reviews the importance of validating sham devices as part of finalizing the design for larger-scale prospective randomized controlled trials in patients with chronic headache as well as the results of a prospective, single-blind trial to validate two potential sham noninvasive thermal nerve block devices. Study participants were trained to self-administer thermal nerve block treatment using sham devices in an office visit. Two different sham systems with different temperature profiles were assessed. Devices were offered for patients to use daily at-home for one week to assess the durability of sham placebo effects before participants were given active treatment in a second office visit followed by another optional week of self-administered active treatment at-home use. Sham treatments reduced pain scores by an average of 31% from 6.0 ± 2.3 to 4.3 ± 3.3, including two participants who fell asleep during the in-office treatment and woke up with no pain, but whose pain recurred after returning home during at-home use of the sham system. In-office active treatments reduced pain scores by 52% from 6.7 ± 2.1 to 3.3 ± 2.9 with sustained pain relief during optional at-home use. Successful blinding for the study was confirmed with an ideal Bang’s Blinding Index of 0 and an ideal James’ Blinding Index of 1. Both the sham and active treatments were viewed by participants as highly credible, and credibility increased from the beginning to end of sham treatments on average. Full article

Paraquat (PQ), rotenone (RO), and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) are neurotoxicants that can damage human health. Exposure to these neurotoxicants has been linked to neurodegeneration, particularly Parkinson’s disease. However, their mechanisms of action have not been fully elucidated, nor has the relative vulnerability of neuronal subtypes to their exposures. To address this, the current study investigated the cytotoxic effects of PQ, RO, and MPTP and their relative effects on cellular bioenergetics and oxidative stress on undifferentiated human neuroblastoma (SH-SY5Y) cells and those differentiated to dopaminergic (DA) or cholinergic (CH) phenotypes. The tested neurotoxicants were all cytotoxic to the three cell phenotypes that correlated with both concentration and exposure duration. At half-maximal effective concentrations (EC₅₀s), there were significant reductions in cellular ATP levels and reduced activity of the mitochondrial complexes I and III, with a parallel increase in lactate production. PQ at 10 µM significantly decreased ATP production and mitochondrial complex III activity only in DA cells. RO was the most potent inhibitor of mitochondrial complex 1 and did not inhibit mitochondrial complex III even at concentrations that induced a 50% loss of cell viability. MPTP was the most potent toxicant in undifferentiated cells. All neurotoxicants significantly increased reactive oxygen species, lipid peroxidation, and nuclear expression of Nrf2, with a corresponding inhibition of the antioxidant enzymes catalase and superoxide dismutase. At a 10 µM exposure to PQ or RO, oxidative stress biomarkers were significant in DA cells. Collectively, this study underscores the importance of mitochondrial dysfunction and oxidative stress in PQ, RO, and MPTP-induced cytotoxicity and that neuronal phenotypes display differential vulnerability to these neurotoxicants. Full article

It has been observed that in some people in the acute phase of ischemic stroke (IS) there is a tendency to shift the body weight towards the side more affected by the disease and a tendency to spontaneous movements of the upper and/or lower limbs (not covered by the neurological syndrome). The purposes of this study were: to define the kind of behavior observed, and to select symptoms which can predict its occurrence. Participants (n = 222) hospitalized due to first-time IS were assigned to three groups. A: 78 patients with no lateralization of the neurological syndrome (lateralization of the neurological syndrome—LoNS); B: 109 patients with LoNS; O+ group: 35 patients, who at the beginning of hospitalization presented, apart from LoNS, characteristic motor symptoms performed by the less affected side. Patients underwent therapy depending on the neurological symptoms. If the patient showed potential symptoms of a new phenomenon, overactivity of the less affected side (OLAS), a trial therapy (focused on this behavior) was used to confirm it. The predictive symptoms, selected among these from the index day, for the occurrence of OLAS in sitting were distinguished: asymmetry in supine posture and simple, repetitive movements of the nonparetic upper extremity. Full article

Exposure to metal mixtures is recognized as a real-life scenario, needing novel studies that can assess their complex effects on brain development. There is still a significant public health concern associated with chronic low levels of metal exposure. In contrast to other metals, these three metals (As, Pb, and Mn) are commonly found in various environmental and industrial contexts. In addition to additive or synergistic interactions, concurrent exposure to this metal mixture may also have neurotoxic effects that differ from those caused by exposure to single components. The NMDA receptor and several important signaling proteins are involved in learning, memory, and synaptic plasticity in the hippocampus, including CaMKII, postsynaptic density protein-95 (PSD-95), synaptic Ras GTPase activating protein (SynGAP), a negative regulator of Ras-MAPK activity, and CREB. We hypothesized that alterations in the above molecular players may contribute to metal mixture developmental neurotoxicity. Thus, the aim of this study was to investigate the effect of these metals and their mixture at low doses (As 4 mg, Pb 4 mg, and Mn 10 mg/kg bw/p.o) on NMDA receptors and their postsynaptic signaling proteins during developing periods (GD6 to PD59) of the rat brain. Rats exposed to As, Pb, and Mn individually or at the same doses in a triple-metal mixture (MM) showed impairments in learning and memory functions in comparison to the control group rats. Declined protein expressions of NR2A, PSD-95, p- CaMKII, and pCREB were observed in the metal mix-exposed rats, while the expression of SynGAP was found to be enhanced in the hippocampus as compared to the controls on PD60. Thereby, our data suggest that alterations in the NMDA receptor complex and postsynaptic signaling proteins could explain the cognitive dysfunctions caused by metal-mixture-induced developmental neurotoxicity in rats. These outcomes indicate that incessant metal mixture exposure may have detrimental consequences on brain development. Full article

When therapists provide teletherapy they can choose between teletherapy via phone and teletherapy via videoconferencing, however, little is known about differences between using these two teletherapy formats. We aimed to compare therapists’ attitudes, level of professional self-doubt, and experience of the therapeutic relationship in sessions conducted via phone versus via videoconferencing. We administered an online survey to 117 therapists who had experience with sessions both via phone and videoconferencing. The results suggested that therapists’ attitudes and perceptions of the therapeutic relationship were similar. However, therapists’ level of professional self-doubt was higher in sessions conducted via videoconferencing. Therapists with previous experience of conducting teletherapy via phone perceived phone sessions more positively. Thus, familiarity with videoconferencing technology might be more important in shaping therapists’ attitudes and confidence than the type of technology per se. This highlights the importance of practicing with new technologies. Full article

Stroke is one of the leading causes of disability around the world, presenting unique challenges in motor development during the rehabilitation process. Based on studies in movement and sports science, thorough knowledge has accumulated on the development of movement skills. Through the works of Nikolai Bernstein, it has been established that when learning new skills, people tend to first simplify coordination by ‘freezing’ their degrees of freedom, after which they start building efficiency by ‘releasing’ specific degrees of freedom. If a similar pattern of development can be established post-stroke, it would imply that lessons learned in sports skill acquisition can also be implemented to optimize stroke rehabilitation. The current scoping review aims to assess whether the Bernsteinian freezing-to-releasing stages of learning also apply to developing whole-body movement skills after stroke. To this end, we systematically screened the existing literature for studies involving a longitudinal measure of whole-body coordination after a stroke. Only five articles met the criteria for inclusion, indicating a gap in research on this topic. Based on the observations within these articles, we could neither confirm nor reject whether the freezing-to-releasing process can apply after a stroke. We could, however, hypothesize a detailed description of the freezing-to-releasing process, which can be assessed in future works. Full article

This paper investigates the influence of gestures on foreign language (FL) vocabulary learning. In this work, we first address the state of the art in the field and then delve into the research conducted in our lab (three experiments already published) in order to finally offer a unified theoretical interpretation of the role of gestures in FL vocabulary learning. In Experiments 1 and 2, we examined the impact of gestures on noun and verb learning. The results revealed that participants exhibited better learning outcomes when FL words were accompanied by congruent gestures compared to those from the no-gesture condition. Conversely, when meaningless or incongruent gestures were presented alongside new FL words, gestures had a detrimental effect on the learning process. Secondly, we addressed the question of whether or not individuals need to physically perform the gestures themselves to observe the effects of gestures on vocabulary learning (Experiment 3). Results indicated that congruent gestures improved FL word recall when learners only observed the instructor’s gestures (“see” group) and when they mimicked them (“do” group). Importantly, the adverse effect associated with incongruent gestures was reduced in the “do” compared to that in the “see” experimental group. These findings suggest that iconic gestures can serve as an effective tool for learning vocabulary in an FL, particularly when the gestures align with the meaning of the words. Furthermore, the active performance of gestures helps counteract the negative effects associated with inconsistencies between gestures and word meanings. Consequently, if a choice must be made, an FL learning strategy in which learners acquire words while making gestures congruent with their meaning would be highly desirable. Full article

Flumazenil is an allosteric modulator of the γ-aminobutyric acid-A receptor (GABA_AR) benzodiazepine binding site that could normalize neuronal signaling and improve motor impairments in Parkinson’s disease (PD). Little is known about how regional GABA_AR availability affects motor symptoms. We investigated the relationship between regional availability of GABA_AR benzodiazepine binding sites and motor impairments in PD. Methods: A total of 11 Patients with PD (males; mean age 69.0 ± 4.6 years; Hoehn and Yahr stages 2–3) underwent [¹¹C]flumazenil GABA_AR benzodiazepine binding site and [¹¹C]dihydrotetrabenazine vesicular monoamine transporter type-2 (VMAT2) PET imaging and clinical assessment. Stepwise regression analysis was used to predict regional cerebral correlates of the four cardinal UPDRS motor scores using cortical, striatal, thalamic, and cerebellar flumazenil binding estimates. Thalamic GABA_AR availability was selectively associated with axial motor scores (R² = 0.55, F = 11.0, β = −6.4, p = 0.0009). Multi-ligand analysis demonstrated significant axial motor predictor effects by both thalamic GABA_AR availability (R² = 0.47, β = −5.2, F = 7.2, p = 0.028) and striatal VMAT2 binding (R² = 0.30, β = −3.9, F = 9.1, p = 0.019; total model: R² = 0.77, F = 11.9, p = 0.0056). Post hoc analysis demonstrated that thalamic [¹¹C]methyl-4-piperidinyl propionate cholinesterase PET and K₁ flow delivery findings were not significant confounders. Findings suggest that reduced thalamic GABA_AR availability correlates with worsened axial motor impairments in PD, independent of nigrostriatal degeneration. These findings may augur novel non-dopaminergic approaches to treating axial motor impairments in PD. Full article

Traumatic brain injury (TBI) is an important health issue for the worldwide population, as it causes long-term pathological consequences for a diverse group of individuals. We are yet to fully elucidate the significance of TBI polypathologies, such as neuroinflammation and tau hyperphosphorylation, and their contribution to the development of chronic traumatic encephalopathy (CTE) and other neurological conditions. To advance our understanding of TBI, it is necessary to replicate TBI in preclinical models. Commonly used animal models include the weight drop model; these methods model human TBI in various ways and in different animal species. However, animal models have not demonstrated their clinical utility for identifying therapeutic interventions. Many interventions that were successful in improving outcomes for animal models did not translate into clinical benefit for patients. It is important to review current animal models and discuss their strengths and limitations within a TBI context. Modelling human TBI in animals encounters numerous challenges, yet despite these barriers, the TBI research community is working to overcome these difficulties. Developments include advances in biomarkers, standardising, and refining existing models. This progress will improve our ability to model TBI in animals and, therefore, enhance our understanding of TBI and, potentially, how to treat it. Full article

The Special Issue “The Body in Neurosciences: Representation, Perception and Space Processing” deals with the understanding of body processing in terms of the multisensorial perception of bodily related information, interoception, and mental representation, as well as its relationship with the peripersonal, interpersonal, and extrapersonal spaces, integrating findings from normal and pathological functioning [...] Full article

Zaleplon is a positive allosteric modulator of the γ-aminobutyric acid (GABA)_A receptor approved for the short-term treatment of insomnia. Previous publications on zaleplon have not addressed the proteins involved in its mechanism of action but have mostly referred to behavioral or pharmacological studies. Since both GABAergic and glutamatergic signaling have been shown to regulate wakefulness and sleep, we examined the effects of prolonged zaleplon treatment (0.625 mg/kg for 5 days) on these systems in the hippocampus of male Wistar rats. Western blot and immunohistochemical analyses showed that the upregulated components of GABAergic signaling (glutamate decarboxylase, vesicular GABA transporter, GABA, and α1 subunit of the GABA_A receptor) were accompanied by increased protein levels in the glutamatergic system (vesicular glutamate transporter 1 and NR1, NR2A, and NR2B subunits of N-methyl-d-aspartate receptor). Our results, showing that zaleplon enhances GABA neurotransmission in the hippocampus, were not surprising. However, we found that treatment also increased glutamatergic signaling. This could be the result of the downregulation of adenosine A1 receptors, important modulators of the glutamatergic system. Further studies are needed to investigate the effects of the zaleplon-induced increase in hippocampal glutamatergic neurotransmission and the possible involvement of the adenosine system in zaleplon’s mechanism of action. Full article

The study aimed to differentiate experts from novices in laparoscopic surgery tasks using electroencephalogram (EEG) topographic features. A microstate-based common spatial pattern (CSP) analysis with linear discriminant analysis (LDA) was compared to a topography-preserving convolutional neural network (CNN) approach. Expert surgeons (N = 10) and novice medical residents (N = 13) performed laparoscopic suturing tasks, and EEG data from 8 experts and 13 novices were analysed. Microstate-based CSP with LDA revealed distinct spatial patterns in the frontal and parietal cortices for experts, while novices showed frontal cortex involvement. The 3D CNN model (ESNet) demonstrated a superior classification performance (accuracy > 98%, sensitivity 99.30%, specificity 99.70%, F1 score 98.51%, MCC 97.56%) compared to the microstate based CSP analysis with LDA (accuracy ~90%). Combining spatial and temporal information in the 3D CNN model enhanced classifier accuracy and highlighted the importance of the parietal–temporal–occipital association region in differentiating experts and novices. Full article

It is well known that exercise promotes health and wellness, both mentally and physiologically. It has been shown to play a protective role in many diseases, including cardiovascular, neurological, and psychiatric diseases. The present study examined the effects of aerobic exercise on brain glucose metabolic activity in response to chronic cocaine exposure in female Lewis rats. Rats were divided into exercise and sedentary groups. Exercised rats underwent treadmill running for six weeks and were compared to the sedentary rats. Using positron emission tomography (PET) and [18F]-Fluorodeoxyglucose (FDG), metabolic changes in distinct brain regions were observed when comparing cocaine-exposed exercised rats to cocaine-exposed sedentary rats. This included activation of the secondary visual cortex and inhibition in the cerebellum, stria terminalis, thalamus, caudate putamen, and primary somatosensory cortex. The functional network of this brain circuit is involved in sensory processing, fear and stress responses, reward/addiction, and movement. These results show that chronic exercise can alter the brain metabolic response to cocaine treatment in regions associated with emotion, behavior, and the brain reward cascade. This supports previous findings of the potential for aerobic exercise to alter the brain’s response to drugs of abuse, providing targets for future investigation. These results can provide insights into the fields of exercise neuroscience, psychiatry, and addiction research. Full article

Recent research emphasizes the significance of studying the quality of life of schizophrenia patients, considering the complex nature of the illness. Identifying neuronal markers for early diagnosis and treatment is crucial. Reelin (RELN) stands out among these markers, with genetic studies highlighting its role in mental health. Suppression of RELN expression may contribute to cognitive deficits by limiting dendritic proliferation, affecting neurogenesis, and leading to improper neuronal circuits. Although the physiological function of reelin is not fully understood, it plays a vital role in hippocampal cell stratification and neuroglia formation. This analysis explores reelin’s importance in the nervous system, shedding light on its impact on mental disorders such as schizophrenia, paving the way for innovative therapeutic approaches, and at the same time, raises the following conclusions: increased methylation levels of the RELN gene in patients with a diagnosis of schizophrenia results in a multiple decrease in the expression of reelin, and monitoring of this indicator, i.e., methylation levels, can be used to monitor the severity of symptoms in the course of schizophrenia. Full article

Naming decline is one of the most common symptoms of primary progressive aphasia (PPA). Most studies on anomia in PPA are performed without taking into account PPA variants, especially for action naming. Only limited data are available for the neuroanatomical basis of anomia considering differences in the pathogenesis of PPAs. The aim of our study is to investigate the associations between anomia severity for both noun and verb naming and gray matter (GM) atrophy, as well as accompanying functional connectivity (FC) changes in three PPA variants. A total of 17 patients with non-fluent (nfvPPA), 11 with semantic (svPPA), and 9 with logopenic (lvPPA) PPA variants were included in the study and underwent cognitive/naming assessments and brain MRIs. Voxel-based morphometry was performed to evaluate GM volume. A resting-state functional MRI was applied to investigate FC changes in the identified GM areas. The study shows that different brain regions are involved in naming decline in each PPA variant with a predominantly temporal lobe involvement in svPPA, parietal lobe involvement in lvPPA, and frontal lobe involvement in nfvPPA. Separate data for object and action naming in PPA variants are provided. The obtained results mainly correspond to the current understanding of language processing and indicate that the evaluation of language impairments is preferable for each PPA variant separately. A further analysis of larger cohorts of patients is necessary to confirm these preliminary results. Full article

Light and noise are important factors affecting shooting performance, and shooters can exhibit physiological processes that differ from normal shooting when they are subjected to disturbed visual and auditory conditions. The purpose of this study was to explore the neural mechanism of shooting preparation in skilled shooters with visual and auditory limitations. We designed an experiment and recorded the electroencephalograph (EEG) and shooting performance indexes of 40 individuals skilled in marksmanship during the shooting preparation stage under three conditions: low light, noise interference, and a normal environment. EEG relative band power features and event-related desynchronization/synchronization (ERD/ERS) features were extracted and analyzed. The results showed that (1) the average score of the shooters was 8.55 under normal conditions, 7.71 under visually restricted conditions, and 8.50 under auditorily restricted conditions; (2) the relative EEG band power in the frontal lobe (Fp1, Fp2), frontal lobe (F4, F8), left temporal region (T7), central lobe (CP2), and parietal lobe (P3, PO3) in the theta band was significantly lower than in the other two environments (p < 0.05), and there was no significant difference between the power intensity of the shooter in the noisy environment and that in the normal environment; and (3) in the low-light environment, a significant negative correlation was found between the central region, the left and right temporal regions, and the parietal lobe (p < 0.05). These findings provide a basis for further understanding neural mechanisms in the brain during the shooting preparation phase under visually and auditorily restricted conditions. Full article