Editor’s Choice Articles

Transcranial direct current stimulation (tDCS) i a non-invasive brain stimulation which is considered to have the potential to improve cognitive impairment in patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD). However, previous studies have been controversial on the therapeutic effect of tDCS. This meta-analysis aimed to evaluate the effects of tDCS on cognitive impairment in patients with MCI and mild-to-moderate AD. Five databases, namely PubMed, EMBASE, MEDLINE, Web of Science and The Cochrane Library, were searched with relative terms to extract the cognitive function changes measured by an objective cognitive scale in the included studies. The meta-analysis results showed that, compared with sham tDCS treatment, the overall cognitive function of patients with AD and MCI was significantly improved (weighted mean difference = 0.99; 95% confidence interval, 0.32 to 1.66; p = 0.004) after tDCS treatment, but the behavioral symptoms, recognition memory function, attention and executive function were not significantly improved. The subgroup analysis showed that the treatment would be more efficacious if the temporal-lobe-related brain areas were stimulated, the number of stimulations was greater than or equal to 10 and the current density was 2.5 mA/cm². Among them, AD patients benefited more than MCI patients. No cognitive improvement was observed in patients with MCI or AD at different follow-up times after treatment. Our meta-analysis provided important evidence for the cognitive enhancement of tDCS in patients with MCI and mild-to-moderate AD and discussed its underlying mechanisms. Full article

Due to its safety, portability, and cheapness, transcranial direct current stimulation (tDCS) use largely increased in research and clinical settings. Despite tDCS’s wide application, previous works pointed out inconsistent and low replicable results, sometimes leading to extreme conclusions about tDCS’s ineffectiveness in modulating behavioral performance across cognitive domains. Traditionally, this variability has been linked to significant differences in the stimulation protocols across studies, including stimulation parameters, target regions, and electrodes montage. Here, we reviewed and discussed evidence of heterogeneity emerging at the intra-study level, namely inter-individual differences that may influence the response to tDCS within each study. This source of variability has been largely neglected by literature, being results mainly analyzed at the group level. Previous research, however, highlighted that only a half—or less—of studies’ participants could be classified as responders, being affected by tDCS in the expected direction. Stable and variable inter-individual differences, such as morphological and genetic features vs. hormonal/exogenous substance consumption, partially account for this heterogeneity. Moreover, variability comes from experiments’ contextual elements, such as participants’ engagement/baseline capacity and individual task difficulty. We concluded that increasing knowledge on inter-dividual differences rather than undermining tDCS effectiveness could enhance protocols’ efficiency and reproducibility. Full article

Background. Loss of olfaction is a well-established early feature of Parkinson’s disease (PD). Although olfactory dysfunction has been widely described as a prodromal feature of PD in the literature, whether it can be considered a biomarker of PD progression is still a matter of debate. Objective. The aim of this work is to define the possible relationship between the progression of olfactory dysfunction and other putative clinical hallmarks of PD over time, through a systematic review of the current literature. Methods. We conducted a systematic review of the literature on PubMed from inception to March 2022. We included only longitudinal studies conducted on patients with diagnosis of idiopathic PD who underwent olfactory function testing at baseline and repeated it at least once during follow-up. Results. Among 5740 records identified through database searching, nine longitudinal studies met full criteria and underwent data extraction. Conclusions. Olfaction seemed to decrease over time, albeit with a degree of fluctuation. Moreover, smell detection ability seems to deteriorate more rapidly in the early phase of disease, indicating a possible association with disease progression. More studies are needed to better understand the role of olfaction as a biomarker of PD progression over time. Full article

A major malignant trait of gliomas is their remarkable infiltration capacity. When glioma develops, the tumor cells have already reached the distant part. Therefore, complete removal of the glioma is impossible. Recently, research on the involvement of the tumor microenvironment in glioma invasion has advanced. Local hypoxia triggers cell migration as an environmental factor. The transcription factor hypoxia-inducible factor (HIF) -1α, produced in tumor cells under hypoxia, promotes the transcription of various invasion related molecules. The extracellular matrix surrounding tumors is degraded by proteases secreted by tumor cells and simultaneously replaced by an extracellular matrix that promotes infiltration. Astrocytes and microglia become tumor-associated astrocytes and glioma-associated macrophages/microglia, respectively, in relation to tumor cells. These cells also promote glioma invasion. Interactions between glioma cells actively promote infiltration of each other. Surgery, chemotherapy, and radiation therapy transform the microenvironment, allowing glioma cells to invade. These findings indicate that the tumor microenvironment may be a target for glioma invasion. On the other hand, because the living body actively promotes tumor infiltration in response to the tumor, it is necessary to reconsider whether the invasion itself is friend or foe to the brain. Full article

Diffuse low-grade gliomas (DLGGs) are heterogeneous and poorly circumscribed neoplasms with isolated tumor cells that extend beyond the margins of the lesion depicted on MRI. Efforts to demarcate the glioma core from the surrounding healthy brain led us to define an intermediate region, the so-called peritumoral zone (PTZ). Although most studies about PTZ have been conducted on high-grade gliomas, the purpose here is to review the cellular, metabolic, and radiological characteristics of PTZ in the specific context of DLGG. A better delineation of PTZ, in which glioma cells and neural tissue strongly interact, may open new therapeutic avenues to optimize both functional and oncological results. First, a connectome-based “supratotal” surgical resection (i.e., with the removal of PTZ in addition to the tumor core) resulted in prolonged survival by limiting the risk of malignant transformation, while improving the quality of life, thanks to a better control of seizures. Second, the timing and order of (neo)adjuvant medical treatments can be modulated according to the pattern of peritumoral infiltration. Third, the development of new drugs specifically targeting the PTZ could be considered from an oncological (such as immunotherapy) and epileptological perspective. Further multimodal investigations of PTZ are needed to maximize long-term outcomes in DLGG patients. Full article

Dopamine is a neurotransmitter that plays a crucial role in adaptive behavior. A wealth of studies suggests obesity-related alterations in the central dopamine system. The most direct evidence for such differences in humans comes from molecular neuroimaging studies using positron emission tomography (PET) and single-photon emission computed tomography (SPECT). The aim of the current review is to give a comprehensive overview of molecular neuroimaging studies that investigated the relation between BMI or weight status and any dopamine target in the striatal and midbrain regions of the human brain. A structured literature search was performed and a summary of the extracted findings are presented for each of the four available domains: (1) D2/D3 receptors, (2) dopamine release, (3) dopamine synthesis, and (4) dopamine transporters. Recent proposals of a nonlinear relationship between severity of obesity and dopamine imbalances are described while integrating findings within and across domains, after which limitations of the review are discussed. We conclude that despite many observed associations between obesity and substrates of the dopamine system in humans, it is unlikely that obesity can be traced back to a single dopaminergic cause or consequence. For effective personalized prevention and treatment of obesity, it will be crucial to identify possible dopamine (and non-dopamine) profiles and their functional characteristics. Full article

Since the outbreak of the SARS-CoV-2 pandemic, olfactory disorders have been reported as a frequent symptom of COVID-19; however, its pathogenesis is still debated. The aim of this review is to summarize the current understanding of the pathogenesis of smell impairment in the course of COVID-19 and to highlight potential avenues for future research on this issue. Several theories have been proposed to explain the pathogenesis of COVID-19-related anosmia, including nasal obstruction and rhinorrhea, oedema of the olfactory cleft mucosa, olfactory epithelial damage either within the olfactory receptor cells or the supporting non-neural cells (either direct or immune-mediated), damage to the olfactory bulb, and impairment of the central olfactory pathways. Although the pathogenesis of COVID-19-related anosmia is still not fully elucidated, it appears to be mainly due to sensorineural damage, with infection of the olfactory epithelium support cells via the ACE1 receptor and disruption of the OE caused by immense inflammatory reaction, and possibly with direct olfactory sensory neurons infection mediated by the NRP-1 receptor. Involvement of the higher olfactory pathways and a conductive component of olfactory disorders, as well as genetic factors, may also be considered. Full article

Food intake regulation in humans is a complex process controlled by the dynamic interaction of homeostatic and hedonic systems. Homeostatic regulation is controlled by appetitive signals from the gut, adipose tissue, and the vagus nerve, while conscious and unconscious reward processes orchestrate hedonic regulation. On the one hand, sight, smell, taste, and texture perception deliver potent food-related feedback to the central nervous system (CNS) and influence brain areas related to food reward. On the other hand, macronutrient composition stimulates the release of appetite signals from the gut, which are translated in the CNS into unconscious reward processes. This multi-level regulation process of food intake shapes and regulates human ingestive behavior. Identifying the interface between hormones, neurotransmitters, and brain areas is critical to advance our understanding of conditions like obesity and develop better therapeutical interventions. Neuroimaging studies allow us to take a glance into the central nervous system (CNS) while these processes take place. This review focuses on the available neuroimaging evidence to describe this interaction between the homeostatic and hedonic components in human food intake regulation. Full article

The main neurotransmitter in the brain responsible for the inhibition of neuronal activity is γ-aminobutyric acid (GABA). It plays a crucial role in circuit formation during development, both via its primary effects as a neurotransmitter and also as a trophic factor. The GABA_B receptors (GABA_BRs) are G protein-coupled metabotropic receptors; on one hand, they can influence proliferation and migration; and, on the other, they can inhibit cells by modulating the function of K⁺ and Ca²⁺ channels, doing so on a slower time scale and with a longer-lasting effect compared to ionotropic GABA_A receptors. GABA_BRs are expressed pre- and post-synaptically, at both glutamatergic and GABAergic terminals, thus being able to shape neuronal activity, plasticity, and the balance between excitatory and inhibitory synaptic transmission in response to varying levels of extracellular GABA concentration. Furthermore, given their subunit composition and their ability to form complexes with several associated proteins, GABA_BRs display heterogeneity with regard to their function, which makes them a promising target for pharmacological interventions. This review will describe (i) the latest results concerning GABA_BRs/GABA_BR-complex structures, their function, and the developmental time course of their appearance and functional integration in the brain, (ii) their involvement in manifestation of various pathophysiological conditions, and (iii) the current status of preclinical and clinical studies involving GABA_BR-targeting drugs. Full article

In recent years, applications of the network science to electrophysiological data have increased as electrophysiological techniques are not only relatively low cost, largely available on the territory and non-invasive, but also potential tools for large population screening. One of the emergent methods for the study of functional connectivity in electrophysiological recordings is graph theory: it allows to describe the brain through a mathematic model, the graph, and provides a simple representation of a complex system. As Alzheimer’s and Parkinson’s disease are associated with synaptic disruptions and changes in the strength of functional connectivity, they can be well described by functional connectivity analysis computed via graph theory. The aim of the present review is to provide an overview of the most recent applications of the graph theory to electrophysiological data in the two by far most frequent neurodegenerative disorders, Alzheimer’s and Parkinson’s diseases. Full article

Background: With 10 vaccines approved by the WHO and nearly 48% of people fully vaccinated worldwide, we have observed several individual case studies of neurological manifestations post-COVID-19 vaccination. Through this systematic review, we aim to discern these CNS and PNS manifestations following the COVID-19 vaccine to help produce methods to mitigate them. Methods: We conducted a thorough literature search of Google Scholar and PubMed from 1 December 2020 until 10 October 2021 and included all the case studies of COVID-19 vaccine-associated neurological side effects. The literature search and data analysis were performed by two independent reviewers according to prespecified inclusion and exclusion criteria using PRISMA. Results: The most common CNS manifestation was CVST (14.47%), found in females (64%) younger than 50 years (71%) after the first AstraZeneca dose (93%). Others included CNS demyelinating disorders (TM, ADEM, MS, NMOSD) (9.30%), encephalopathy/encephalitis (3.10%), and others (4.13%). The most common PNS manifestation was GBS (14.67%) found in males (71%) older than 50 years (79%), followed by Bell’s palsy (5.24%) and others (2.10%). Most occurred with the AstraZeneca (28.55%), Pfizer-BioNTech (9.18%), and Moderna (8.16%) vaccines. Nine (64%) out of the 14 patients with CVST died. However, most cases overall (42 out of 51) were non-fatal (82%). Conclusion: Several CNS and PNS adverse events have occurred post-COVID-19 vaccination, including CVST, GBS, and TM. High vigilance with early identification and treatment leads to better outcomes. Further studies with non-vaccinated controls might help in understanding the pathophysiologic mechanisms of these neurological manifestations following COVID-19 vaccination. Full article

Background: patients with a subarachnoid hemorrhage (SAH) might need a flow diverter (FD) placement for complex acutely ruptured intracranial aneurysms (IAs). We conducted a meta-analysis and developed a prediction model to estimate the favorable clinical outcome after the FD treatment in acutely ruptured IAs. Methods: a systematic literature search was performed from 2010 to January 2021 in PubMed and Embase databases. Studies with more than five patients treated with FDs within fifteen days were included. In total, 1157 studies were identified. The primary outcome measure was the favorable clinical outcome (mRS 0–2). Secondary outcome measures were complete occlusion rates, aneurysm rebleeding, permanent neurologic deficit caused by procedure-related complications, and all-cause mortality. A prediction model was constructed using individual patient-level data. Results: 26 retrospective studies with 357 patients and 368 aneurysms were included. The pooled rates of the favorable clinical outcome, mortality, and complete aneurysm occlusion were 73.7% (95% CI 64.7–81.0), 17.1% (95% CI 13.3–21.8), and 85.6% (95% CI 80.4–89.6), respectively. Rebleeding occurred in 3% of aneurysms (11/368). The c-statistic of the final model was 0.83 (95% CI 0.76–0.89). All the studies provided a very low quality of evidence. Conclusions: FD treatment can be considered for complex ruptured IAs. Despite high complication rates, the pooled clinical outcomes seem favorable. The prediction model needs to be validated by larger prospective studies before clinical application. Full article

Eating disorders (EDs) are serious, life-threatening psychiatric conditions associated with physical and psychosocial impairment, as well as high morbidity and mortality. Given the chronic refractory nature of EDs and the paucity of evidence-based treatments, there is a pressing need to identify novel approaches for this population. The noncompetitive N-methyl-D-aspartate receptor (NMDAr) antagonist, ketamine, has recently been approved for treatment-resistant depression, exerting rapid and robust antidepressant effects. It is now being investigated for several new indications, including obsessive–compulsive, post-traumatic, and substance use disorder, and shows transdiagnostic potential for EDs, particularly among clinical nonresponders. Hence, the aim of this review is to examine contemporary findings on the treatment of EDs with ketamine, whether used as a primary, adjunctive, or combination psychopharmacotherapy. Avenues for future research are also discussed. Overall, results are encouraging and point to therapeutic value; however, are limited to case series and reports on anorexia nervosa. Further empirical research is thus needed to explore ketamine efficacy across ED subgroups, establish safety profiles and optimize dosing, and develop theory-driven, targeted treatment strategies at the individual patient level. Full article

Metals—especially iron, copper and manganese—are important elements of brain functions and development. Metal-dysregulation homeostasis is associated with brain-structure damage to the motor, cognitive and emotional systems, and leads to neurodegenerative processes. There is more and more evidence that specialized cognitive and motor exercises can enhance brain function and attenuate neurodegeneration in mechanisms, such as improving neuroplasticity by altering the synaptic structure and function in many brain regions. Psychological and physical methods of rehabilitation are now becoming increasingly important, as pharmacological treatments for movement, cognitive and emotional symptoms are limited. The present study describes physical and cognitive rehabilitation methods of patients associated with metal-induced neurotoxicity such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, Huntington’s disease and Wilson’s disease. In our review, we describe physical (e.g., virtual-reality environments, robotic-assists training) and psychological (cognitive training, cognitive stimulation, neuropsychological rehabilitation and cognitive-behavioral and mindfulness-based therapies) methods, significantly improving the quality of life and independence of patients associated with storage diseases. Storage diseases are a diverse group of hereditary metabolic defects characterized by the abnormal cumulation of storage material in cells. This topic is being addressed due to the fact that rehabilitation plays a vital role in the treatment of neurodegenerative diseases. Unfortunately so far there are no specific guidelines concerning physiotherapy in neurodegenerative disorders, especially in regards to duration of exercise, type of exercise and intensity, as well as frequency of exercise. This is in part due to the variety of symptoms of these diseases and the various levels of disease progression. This further proves the need for more research to be carried out on the role of exercise in neurodegenerative disorder treatment. Full article

Physical activity leads to well-established health benefits. Current efforts to enhance physical activity have targeted mainly socioeconomic factors. However, despite these efforts, only a small number of adults engage in regular physical activity to the point of meeting current recommendations. Evidence collected in rodent models and humans establish a strong central nervous system component that regulates physical activity behavior. In particular, dopaminergic pathways in the central nervous system are among the best-characterized biological mechanisms to date with respect to regulating reward, motivation, and habit formation, which are critical for establishing regular physical activity. Herein, we discuss evidence for a role of brain dopamine in the regulation of voluntary physical activity behavior based on selective breeding and pharmacological studies in rodents, as well as genetic studies in both rodents and humans. While these studies establish a role of dopamine and associated mechanisms in the brain in the regulation of voluntary physical activity behavior, there is clearly need for more research on the underlying biology involved in motivation for physical activity and the formation of a physical activity habit. Such knowledge at the basic science level may ultimately be translated into better strategies to enhance physical activity levels within the society. Full article

Pain and suffering in persons with disorders of consciousness (DoC) remain poorly understood, frequently unaddressed or inadequately addressed, and controversial on numerous levels. This narrative literature review will address a number of critical issues germane to pain and suffering in this challenging group of patients, providing an introductory overview of the topic, perspectives on current knowledge regarding pain pathoanatomy and pathophysiology, and a review of common pain generators and factors that can lead to the chronifcation of pain. Caveats on bedside pain assessment challenges, as well as electrophysiologic and neuroimaging findings in these patients, will also be explored. Pain management techniques, including non-pharmacological and pharmacological, will be reviewed. Ethical considerations in the context of pain and suffering in persons with disorders of consciousness will round out the review prior to our concluding comments. Full article

Mathematical performance implies a series of numerical and mathematical skills (both innate and derived from formal training) as well as certain general cognitive abilities that, if inadequate, can have a cascading effect on mathematics learning. These latter skills were the focus of the present systematic review. Method: The reviewing process was conducted according to the PRISMA statement. We included 46 studies comparing school-aged children’s performance with and without math difficulties in the following cognitive domains: processing speed, phonological awareness, short- and long-term memory, executive functions, and attention. Results: The results showed that some general cognitive domains were compromised in children with mathematical difficulties (i.e., executive functions, attention, and processing speed). Conclusions: These cognitive functions should be evaluated during the diagnostic process in order to better understand the child’s profile and propose individually tailored interventions. However, further studies should investigate the role of skills that have been poorly investigated to date (e.g., long-term memory and phonological awareness). Full article

Tics can be associated with neurological disorders and are thought to be the result of dysfunctional basal ganglia pathways. In Tourette Syndrome (TS), excess dopamine in the striatum is thought to excite the thalamo-cortical circuits, producing tics. When external stressors activate the hypothalamic-pituitary-adrenal (HPA) axis, more dopamine is produced, furthering the excitation of tic-producing pathways. Emotional processing structures in the limbic are also activated during tics, providing further evidence of a possible emotional component in motor ticking behaviors. The purpose of this review is to better understand the relationship between emotional states and ticking behavior. We found support for the notion that premonitory sensory phenomena (PSP), sensory stimulation, and other environmental stressors that impact the HPA axis can influence tics through dopaminergic neurotransmission. Dopamine plays a vital role in cognition and motor control and is an important neurotransmitter in the pathophysiology of other disorders such as obsessive–compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD), which tend to be comorbid with ticking disorders and are thought to use similar pathways. It is concluded that there is an emotional component to ticking behaviors. Emotions primarily involving anxiety, tension, stress, and frustration have been associated with exacerbated tics, with PSP contributing to these feelings. Full article

Aggressive behaviour is at the basis of many harms in society, such as violent crime. The efforts to explain, study, and possibly reduce aggression span various disciplines, including neuroscience. The specific brain networks which are involved in the modulation of aggressive behaviour include cortical asymmetry and brain areas such as the dorsolateral prefrontal cortex (DLPFC), the ventrolateral prefrontal cortex (VLPFC), and the ventromedial prefrontal cortex (VMPFC). Recent non-invasive brain stimulation (NIBS) research suggests that both transcranial direct current stimulation (tDCS) and continuous theta burst stimulation (cTBS) can play a role in the modulation of aggressive behaviour by directly changing brain activity. In this review, we systematically explore and discuss 11 experimental studies that aimed to modulate aggressive behaviour or self-reported aggression using NIBS. Out of these 11 studies, nine significantly up- or downregulated aggression by using tDCS or cTBS targeting the DLPFC, VLPFC or VMPFC. The potential applications of these findings span both the clinical and the forensic psychological domains. However, the results are limited by the methodological heterogeneity in the aggression measures used across the studies, and by their generally small sample sizes. Future research should consider improving the localization and specificity of NIBS by employing neuro-navigational instruments and standardized scoring methods. Full article

Ever since it was first reported in Wuhan, China, the coronavirus-induced disease of 2019 (COVID-19) has become an enigma of sorts with ever expanding reports of direct and indirect effects of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on almost all the vital organ systems. Along with inciting acute pulmonary complications, the virus attacks the cardiac, renal, hepatic, and gastrointestinal systems as well as the central nervous system (CNS). The person-to-person variability in susceptibility of individuals to disease severity still remains a puzzle, although the comorbidities and the age/gender of a person are believed to play a key role. SARS-CoV-2 needs angiotensin-converting enzyme 2 (ACE2) receptor for its infectivity, and the association between SARS-CoV-2 and ACE2 leads to a decline in ACE2 activity and its neuroprotective effects. Acute respiratory distress may also induce hypoxia, leading to increased oxidative stress and neurodegeneration. Infection of the neurons along with peripheral leukocytes’ activation results in proinflammatory cytokine release, rendering the brain more susceptible to neurodegenerative changes. Due to the advancement in molecular biology techniques and vaccine development programs, the world now has hope to relatively quickly study and combat the deadly virus. On the other side, however, the virus seems to be still evolving with new variants being discovered periodically. In keeping up with the pace of this virus, there has been an avalanche of studies. This review provides an update on the recent progress in adjudicating the CNS-related mechanisms of SARS-CoV-2 infection and its potential to incite or accelerate neurodegeneration in surviving patients. Current as well as emerging therapeutic opportunities and biomarker development are highlighted. Full article

Nervous system involvement in patients with SLE, termed neuropsychiatric SLE (NPSLE), constitutes a diagnostic challenge, and its management is still poorly optimised. This review summarises recent insights over the past decade in laboratory biomarkers of diagnosis, monitoring, and prognosis of NPSLE. An initial systematic search in the Medline and Web of Science was conducted to guide the selection of articles. Emerging diagnostic biomarkers in NPSLE that displayed satisfactory ability to discriminate between NPSLE and controls include serum interleukin (IL)-6, microRNA (miR)-23a, miR-155, and cerebrospinal fluid (CSF) α-Klotho. CSF lipocalin-2, macrophage colony-stimulating factor (M-CSF), and immunoglobulin (Ig)M also displayed such ability in two ethnically diverse cohorts. Serum interferon (IFN)-α and neuron specific enolase (NSE) were recently reported to moderately correlate with disease activity in patients with active NPSLE. CSF IL-8, IL-13, and granulocyte colony-stimulating factor (G-CSF) exhibited excellent sensitivity, yet poorer specificity, as predictors of response to therapy in patients with NPSLE. The overall lack of validation studies across multiple and diverse cohorts necessitates further and well-concerted investigations. Nevertheless, we propound CSF lipocalin 2 among molecules that hold promise as reliable diagnostic biomarkers in NPSLE. Full article

Parkinson’s disease (PD) is the second most common neurodegenerative disorder with an unclear etiology and no disease-modifying treatment to date. PD is considered a multifactorial disease, since both genetic and environmental factors contribute to its pathogenesis, although the molecular mechanisms linking these two key disease modifiers remain obscure. In this context, epigenetic mechanisms that alter gene expression without affecting the DNA sequence through DNA methylation, histone post-transcriptional modifications, and non-coding RNAs may represent the key mediators of the genetic–environmental interactions underlying PD pathogenesis. Environmental exposures may cause chemical alterations in several cellular functions, including gene expression. Emerging evidence has highlighted that smoking, coffee consumption, pesticide exposure, and heavy metals (manganese, arsenic, lead, etc.) may potentially affect the risk of PD development at least partially via epigenetic modifications. Herein, we discuss recent accumulating pre-clinical and clinical evidence of the impact of lifestyle and environmental factors on the epigenetic mechanisms underlying PD development, aiming to shed more light on the pathogenesis and stimulate future research. Full article

Background and Objective: Heart rate variability (HRV) as an index of the autonomic nervous system appears to be related to reactivity to experimental pain stimuli. HRV could better explain the contributions of sympathetic and parasympathetic activity response to nociceptive stimulation. The aim of this study was to systematically review and synthesize the current evidence on HRV in relation to the experience of pain in experimental tasks. Databases and Data Treatment: Studies indexed in the PubMed, PsycINFO, MEDLINE, WebOfScience, and Scopus databases were reviewed for eligibility. Studies on the autonomic response (i.e., HRV) to experimentally induced pain in healthy adults were included. Different methods of pain induction were considered (e.g., thermal, pressure, and electrical). Data were synthesized considering the association between HRV and both pain induction and subjective measures of pain. Results: Seventy-one studies were included. The results underline significant change in both the sympathetic and parasympathetic autonomic nervous systems during the painful stimulation independent of the pain induction method. The autonomic reaction to pain could be affected by several factors, such as sex, age, body mass index, breathing patterns, the intensity of the stimulation, and the affective state. Moreover, an association between the autonomic nervous system and the subjective experience of pain was found. Higher parasympathetic activity was associated with better self-regulation capacities and, accordingly, a higher pain inhibition capacity. Conclusions: HRV appears to be a helpful marker to evaluate nociceptive response in experimentally induced pain. Future studies are also needed in clinical samples to understand better the interindividual changes of autonomic response due to pain stimuli. Full article

Orexin peptides comprise two neuropeptides, orexin A and orexin B, that bind two G-protein coupled receptors (GPCRs), orexin receptor 1 (OXR1) and orexin receptor 2 (OXR2). Although cell bodies that produce orexin peptides are localized in a small area comprising the lateral hypothalamus and adjacent regions, orexin-containing fibres project throughout the neuraxis. Although orexins were initially described as peptides that regulate feeding behaviour, research has shown that orexins are involved in diverse functions that range from the modulation of autonomic functions to higher cognitive functions, including reward-seeking, behaviour, attention, cognition, and mood. Furthermore, disruption in orexin signalling has been shown in mood disorders that are associated with low hedonic tone or anhedonia, including depression, anxiety, attention deficit hyperactivity disorder, and addiction. Notably, projections of orexin neurons overlap circuits involved in the modulation of hedonic tone. Evidence shows that orexins may potentiate hedonic behaviours by increasing the feeling of pleasure or reward to various signalling, whereas dysregulation of orexin signalling may underlie low hedonic tone or anhedonia. Further, orexin appears to play a key role in regulating behaviours in motivationally charged situations, such as food-seeking during hunger, or drug-seeking during withdrawal. Therefore, it would be expected that dysregulation of orexin expression or signalling is associated with changes in hedonic tone. Further studies investigating this association are warranted. Full article

Research on traumatic brain injury (TBI) as a result of domestic violence has greatly increased in the past decade, with publications addressing the prevalence, diagnosis, evaluation, and treatment. Although TBI due to domestic violence has recently been found to occur quite frequently, it was not widely understood until the 1990s. Individuals who suffer from domestic violence TBI often experience sequelae such as decreased cognitive functioning, memory loss, and PTSD. The goal of this article is to increase awareness about TBI secondary to domestic violence, with the intent that it will highlight areas for future research on the diagnosis, evaluation, and treatment of TBI in this population. The articles in this study were first found using the search terms traumatic brain injury and domestic violence. Although, in recent years, there has been a significant increase in research on TBI due to domestic violence, the overall conclusion of this review article is that there is still a need for future research in many areas including the effects on minority populations, the effects of COVID-19, and improvements of screening tools. Full article

Hemispheric differences in emotional processing have been observed for over half a century, leading to multiple theories classifying differing roles for the right and left hemisphere in emotional processing. Conventional acceptance of these theories has had lasting clinical implications for the treatment of mood disorders. The theory that the left hemisphere is broadly associated with positively valenced emotions, while the right hemisphere is broadly associated with negatively valenced emotions, drove the initial application of repetitive transcranial magnetic stimulation (rTMS) for the treatment of major depressive disorder (MDD). Subsequent rTMS research has led to improved response rates while adhering to the same initial paradigm of administering excitatory rTMS to the left prefrontal cortex (PFC) and inhibitory rTMS to the right PFC. However, accumulating evidence points to greater similarities in emotional regulation between the hemispheres than previously theorized, with potential implications for how rTMS for MDD may be delivered and optimized in the near future. This review will catalog the range of measurement modalities that have been used to explore and describe hemispheric differences, and highlight evidence that updates and advances knowledge of TMS targeting and parameter selection. Future directions for research are proposed that may advance precision medicine and improve efficacy of TMS for MDD. Full article

Antiphospholipid syndrome (APS) is a common autoimmune pro-thrombotic condition characterised by thrombosis and pregnancy morbidity. There are a broad range of neuropsychiatric manifestations associated with APS, from focal symptoms to more global dysfunction. Patients commonly present with transient ischaemic attacks and ischaemic strokes, with identifiable lesions on brain imaging. However, the underlying pathogenesis remains uncertain in other manifestations, such as cognitive dysfunction, seizures, headache and chorea. The aim is to provide a comprehensive review of the various neuropsychiatric manifestations associated with APS. A detailed literature search was applied to PubMed, including citations from 1983 to December 2021. Full article

Developmental dyslexia is a complex reading disorder involving genetic and environmental factors. After more than a century of research, its etiology remains debated. Two hypotheses are often put forward by scholars to account for the causes of dyslexia. The most common one, the linguistic hypothesis, postulates that dyslexia is due to poor phonological awareness. The alternative hypothesis considers that dyslexia is caused by visual-attentional deficits and abnormal eye movement patterns. This article reviews a series of selected event-related brain potential (ERP) and eye movement studies on the reading ability of dyslexic individuals to provide an informed state of knowledge on the etiology of dyslexia. Our purpose is to show that the two abovementioned hypotheses are not necessarily mutually exclusive, and that dyslexia should rather be considered as a multifactorial deficit. Full article

With growing concerns about COVID-19’s hyperinflammatory condition and its potentially damaging impact on the neurovascular system, there is a need to consider potential treatment options for managing short- and long-term effects on neurological complications, especially cognitive function. While maintaining adequate structure and function of phospholipid in brain cells, citicoline, identical to the natural metabolite phospholipid phosphatidylcholine precursor, can contribute to a variety of neurological diseases and hypothetically toward post-COVID-19 cognitive effects. In this review, we comprehensively describe in detail the potential citicoline mechanisms as adjunctive therapy and prevention of COVID-19-related cognitive decline and other neurologic complications through citicoline properties of anti-inflammation, anti-viral, neuroprotection, neurorestorative, and acetylcholine neurotransmitter synthesis, and provide a recommendation for future clinical trials. Full article

Family caregivers of people with amyotrophic lateral sclerosis (ALS), a severely disabling neurodegenerative disease due to the degeneration of both upper and lower motor neurons, have a very demanding role in managing their relatives, thereby often experiencing heavy care burden. Previous literature has widely highlighted that this situation reduces caregivers’ quality of life and increases their psychological distress and risk of health problems, but there are relatively few studies that focus on psychological interventions for these situations. Family support is more—not less—important during crisis. However, during the COVID-19 pandemic, maintaining public safety has required restricting the physical presence of families for hospitalized patients. Caregivers of ALS patients felt increased sense of loneliness and experienced greater difficulties in the access to both hospital and home assistance. In response, health systems rapidly adapted family-centric procedures and tools to circumvent restrictions on physical presence. In this regard, internet-based and telehealth solutions have been adopted to facilitate the routine, predictable, and structured communication, crucial to family-centered care. This narrative review aims at addressing more current matters on support needs and interventions for improving wellbeing of caregivers of ALS patients. In particular, we aimed at highlighting several gaps related to the complex needs of caregivers of ALS patients, to the interventions carried out in order to respond to these needs, and to the changes that COVID-19 pandemic caused from 2020 to nowadays in clinical managing of ALS patients. Finally, we report ongoing experiences of psychological support for family caregivers of ALS patients through telehealth solutions, which have been reinforced in case of needing of physical distancing during the COVID-19 pandemic. Full article

Multiple Chemical Sensitivity (MCS), a condition also known as Chemical Sensitivity (CS), Chemical Intolerance (CI), Idiopathic Environmental Illness (IEI) and Toxicant Induced Loss of Tolerance (TILT), is an acquired multifactorial syndrome characterized by a recurrent set of debilitating symptoms. The symptoms of this controversial disorder are reported to be induced by environmental chemicals at doses far below those usually harmful to most persons. They involve a large spectrum of organ systems and typically disappear when the environmental chemicals are removed. However, no clear link has emerged among self-reported MCS symptoms and widely accepted objective measures of physiological dysfunction, and no clear dose-response relationship between exposure and symptom reactions has been observed. In addition, the underlying etiology and pathogenic processes of the disorder remain unknown and disputed, although biologic and psychologic hypotheses abound. It is currently debated whether MCS should be considered a clinical entity at all. Nevertheless, in the last few decades MCS has received considerable scientific and governmental attention in light of the many persons reporting this illness. In this review, we provide a general overview of the history, definition, demographics, prevalence, and etiologic challenges in defining and understanding MCS. Full article

The neural mechanisms subserving the processing of abstract concepts remain largely debated. Even within the embodiment theoretical framework, most authors suggest that abstract concepts are coded in a linguistic propositional format, although they do not completely deny the role of sensorimotor and emotional experiences in coding it. To our knowledge, only one recent proposal puts forward that the processing of concrete and abstract concepts relies on the same mechanisms, with the only difference being in the complexity of the underlying experiences. In this paper, we performed a meta-analysis using the Activation Likelihood Estimates (ALE) method on 33 functional neuroimaging studies that considered activations related to abstract and concrete concepts. The results suggest that (1) concrete and abstract concepts share the recruitment of the temporo-fronto-parietal circuits normally involved in the interactions with the physical world, (2) processing concrete concepts recruits fronto-parietal areas better than abstract concepts, and (3) abstract concepts recruit Broca’s region more strongly than concrete ones. Based on anatomical and physiological evidence, Broca’s region is not only a linguistic region mainly devoted to speech production, but it is endowed with complex motor representations of different biological effectors. Hence, we propose that the stronger recruitment of this region for abstract concepts is expression of the complex sensorimotor experiences underlying it, rather than evidence of a purely linguistic format of its processing. Full article

Dyslexia, a specific reading disability, is a common (up to 10% of children) and highly heritable (~70%) neurodevelopmental disorder. Behavioral and molecular genetic approaches are aimed towards dissecting its significant genetic component. In the proposed review, we will summarize advances in twin and molecular genetic research from the past 20 years. First, we will briefly outline the clinical and educational presentation and epidemiology of dyslexia. Next, we will summarize results from twin studies, followed by molecular genetic research (e.g., genome-wide association studies (GWASs)). In particular, we will highlight converging key insights from genetic research. (1) Dyslexia is a highly polygenic neurodevelopmental disorder with a complex genetic architecture. (2) Dyslexia categories share a large proportion of genetics with continuously distributed measures of reading skills, with shared genetic risks also seen across development. (3) Dyslexia genetic risks are shared with those implicated in many other neurodevelopmental disorders (e.g., developmental language disorder and dyscalculia). Finally, we will discuss the implications and future directions. As the diversity of genetic studies continues to increase through international collaborate efforts, we will highlight the challenges in advances of genetics discoveries in this field. Full article

The stomatognathic system is a functional complex of tissues and organs located within the oral and craniofacial cavities. The craniofacial anatomical factors and the biomechanics of the temporomandibular joints affect many systems throughout the body, including the organ of vision. However, few scientific reports have shown a relationship between the organ of vision and the stomatognathic system. The purpose of this review is to provide an overview of connections along neural, muscle-fascial, and biochemical pathways between the organ of vision and the stomatognathic system. Based on the literature presented in this review, the connections between the organ of vision and the stomatognathic system seem undeniable. Understanding the anatomical, physiological, and biochemical interrelationships may allow to explain the interactions between the mentioned systems. According to the current knowledge, it is not possible to indicate the main linking pathway; presumably, it may be a combination of several presented pathways. The awareness of this relationship among dentists, ophthalmologists, physiotherapists, and optometrists should increase for the better diagnosis and treatment of patients. Full article

Biofeedback training is a method commonly used in various fields of life, for example, in medicine, sports training or business. In recent studies, it has been shown that biofeedback, and neurofeedback, can affect the performance of professional athletes. Training based on the neurofeedback method includes exercising the brain waves. The aim of the article is to evaluate the influence of neurofeedback training on the physical fitness of professional athletes representing various sports disciplines, such as judo, volleyball and soccer. Based on 10 scientific papers from various sources, including PubMed, the latest research on neurofeedback and its impact on athletes has been reviewed. On the basis of the literature review from 2012 to 2022 on the neurofeedback method in sports training, it can be stated that this type of practice has a significant impact on physical fitness and sports performance. This review comprised 10 research studies with 491 participants in the neurofeedback groups, and 62 participants in the control group. Two reviewers independently extracted data and evaluated the quality of the studies utilising the PEDro scale. Properly planned and conducted neurofeedback training affects stimulation and improvement of many variables (reducing stress levels, increasing the ability to self-control physiological factors, enhancing behavioural efficiency and meliorating the speed of reaction to a stimulus). Full article

Objective: The coronavirus belongs to the family of Coronaviridae, which are not branched single-stranded RNA viruses. COVID-19 creates respiratory problems and infections ranging from mild to severe. The virus features mechanisms that serve to delay the cellular immune response. The host’s response is responsible for the pathological process that leads to tissue destruction. Temporomandibular disorders are manifested by painful jaw musculature and jaw joint areas, clicks, or creaks when opening or closing the mouth. All these symptoms can be disabling and occur during chewing and when the patient yawns or even speaks. The pandemic situation has exacerbated anxieties and amplified the vulnerability of individuals. Therefore, from this mechanism, how the COVID-19 pandemic may have increased the incidence of temporomandibular disorders is perceived. The purpose of this review is to evaluate whether COVID-19-related anxiety has caused an increase in temporomandibular dysfunction symptoms in adults to children. Methods: PubMed, Web of Science, Lilacs, and Scopus were systematically searched, until 30 July 2022, to identify studies presenting: the connection between COVID-19 with temporomandibular disorders. Results: From 198 papers, 4 studies were included. Literature studies have shown that the state of uncertainty and anxiety has led to an increase in the incidence of this type of disorder, although not all studies agree. Seventy-three studies were identified after viewing all four search engines; at the end of the screening phase, only four were considered that met the PECO, the planned inclusion, and the exclusion criteria. All studies showed a statistically significant correlation between temporomandibular disorders and COVID-19 with a p < 0.05. Conclusions: All studies agreed that there is an association between COVID-19 and increased incidence of temporomandibular disorders. Full article

The extent of resection beyond the enhancing core (EC) in glioblastoma IDH-wild type (GBM, IDHwt) is one of the most debated topics in neuro-oncology. Indeed, it has been demonstrated that local disease recurrence often arises in peritumoral areas and that radiologically-defined FLAIR hyperintensity areas of GBM IDHwt are often visible beyond the conventional EC. Therefore, the need to extend the surgical resection also to the FLAIR hyperintensity areas is a matter of debate. Since little is known about the histological composition of FLAIR hyperintensity regions, in this study we aimed to provide a comprehensive description of the histological features of EC and FLAIR hyperintensity regions sampled intraoperatively using neuronavigation and 5-aminolevulinic acid (5-ALA) fluorescence, in 33 patients with GBM, IDHwt. Assessing a total 109 histological samples, we found that FLAIR areas consisted in: (i) fragments of white matter focally to diffusely infiltrated by tumor cells in 76% of cases; (ii) a mixture of white matter with reactive astrogliosis and grey matter with perineuronal satellitosis in 15% and (iii) tumor tissue in 9%. A deeper knowledge of the histology of FLAIR hyperintensity areas in GBM, IDH-wt may serve to better guide neurosurgeons on the choice of the most appropriate surgical approach in patients with this neoplasm. Full article

Working memory (WM) plays a crucial role in the development of arithmetic ability. However, research findings related to which factors influence the relationship between WM and arithmetic skills are inconsistent. The present meta-analysis aimed to examine the links between WM and arithmetic in primary school children and investigate whether this is dependent on WM domains (i.e., verbal, visual, spatial), child age, arithmetic operation type, and arithmetic task type. A total of 11,224 participants with an age range of 6- to 12 years, from 55 independent samples were included in the meta-analysis. Analysis of 46 studies with 187 effect sizes revealed an overall significant and medium correlation between WM and arithmetic. Heterogeneity analyses indicated that verbal WM showed a stronger correlation with arithmetic than visuospatial WM, and that correlations between verbal WM and arithmetic declined with age, whereas correlations between spatial-sequential, and spatial-simultaneous WM and arithmetic remained stable throughout development. Addition and subtraction were more involved in verbal WM than multiplication and division. Moreover, mental and written arithmetic showed comparable correlations with WM in all domains. These findings suggest moderation effects of WM domains, age, and operation types in the WM-arithmetic relationship and highlight the significant role of verbal WM in arithmetic ability in primary school children. Full article

Motor and cognitive rehabilitation in individuals with traumatic brain injury (TBI) is a growing field of clinical and research interest. In fact, novel rehabilitative approaches allow a very early verticalization and gait training through robotic devices and other innovative tools boosting neuroplasticity, thanks to the high-intensity, repetitive and task-oriented training. In the same way, cognitive rehabilitation is also evolving towards advanced interventions using virtual reality (VR), computer-based approaches, telerehabilitation and neuromodulation devices. This review aimed to systematically investigate the existing evidence concerning the role of innovative technologies in the motor and cognitive neurorehabilitation of TBI patients. We searched and reviewed the studies published in the Cochrane Library, PEDro, PubMed and Scopus between January 2012 and September 2022. After an accurate screening, only 29 papers were included in this review. This systematic review has demonstrated the beneficial role of innovative technologies when applied to cognitive rehabilitation in patients with TBI, while evidence of their effect on motor rehabilitation in this patient population is poor and still controversial. Full article

Temporal interference transcranial alternating current stimulation (TI-tACS) is a new technique of noninvasive brain stimulation. Previous studies have shown the effectiveness of TI-tACS in stimulating brain areas in a selective manner. However, its safety in modulating human brain neurons is still untested. In this study, 38 healthy adults were recruited to undergo a series of neurological and neuropsychological measurements regarding safety concerns before and after active (2 mA, 20/70 Hz, 30 min) or sham (0 mA, 0 Hz, 30 min) TI-tACS. The neurological and neuropsychological measurements included electroencephalography (EEG), serum neuron-specific enolase (NSE), the Montreal Cognitive Assessment (MoCA), the Purdue Pegboard Test (PPT), an abbreviated version of the California Computerized Assessment Package (A-CalCAP), a revised version of the Visual Analog Mood Scale (VAMS-R), a self-assessment scale (SAS), and a questionnaire about adverse effects (AEs). We found no significant difference between the measurements of the active and sham TI-tACS groups. Meanwhile, no serious or intolerable adverse effects were reported or observed in the active stimulation group of 19 participants. These results support that TI-tACS is safe and tolerable in terms of neurological and neuropsychological functions and adverse effects for use in human brain stimulation studies under typical transcranial electric stimulation (TES) conditions (2 mA, 20/70 Hz, 30 min). Full article

Exercise modes can be categorized based on the skills required (open vs. closed skills), which implicates various demands on cognitive skills, especially executive functions (EFs). Thus, their practice may have varying effects on EFs. There is a lack of detailed analysis of cognitive requirements and suitable classification of sports. It is hypothesized that the amount and type of cognitive requirements of sports lead to small effect sizes when comparing open-skill exercising (OSE) and closed-skill exercising (CSE) athletes. The current meta-analysis evaluates the variances in EFs skills caused by particular sport modes. Four research databases (Web of Science, PubMed, ScienceDirect, PsychINFO) were searched for cross-sectional studies in which the authors compare the performance in EF tasks of OSE and CSE athletes. Risk of bias assessment was conducted using funnel plots and two reviewer selection process (overall and subgroup analysis; low risk of publication and selection bias). A total of 19 studies were included, revealing an overall effect size of Hedge’s g = 0.174 (p = 0.157), favoring OSE for the development of EFs. The subgroup analysis revealed the effects for the subdomains of EFs (cognitive flexibility: Hedge’s g = 0.210 > inhibitory control: Hedge’s g = 0.191 > working memory: Hedge’s g = 0.138; p > 0.05), which could be characterized as low to moderate. The hypothesis that studies with the smallest effect sizes compare sport modes with similar cognitive demands was rejected. The paper discusses the differentiation of sports into OSE and CSE and presents new approaches for their categorization. Full article

Background: High-dose ionizing radiation (IR) (>0.5 Gy) is an established risk factor for cognitive impairments, but this cannot be concluded for low-to-moderate IR exposure (<0.5 Gy) in adulthood as study results are inconsistent. The objectives are to summarize relevant epidemiological studies of low-to-moderate IR exposure in adulthood and to assess the risk of non-cancerous CNS diseases. Methods: A systematic literature search of four electronic databases was performed to retrieve relevant epidemiological studies published from 2000 to 2022. Pooled standardized mortality ratios, relative risks, and excess relative risks (ERR) were estimated with a random effect model. Results: Forty-five publications were included in the systematic review, including thirty-three in the quantitative meta-analysis. The following sources of IR-exposure were considered: atomic bomb, occupational, environmental, and medical exposure. Increased dose-risk relationships were found for cerebrovascular diseases incidence and mortality (ERR_pooled per 100 mGy = 0.04; 95% CI: 0.03–0.05; ERR_pooled at 100 mGy = 0.01; 95% CI: −0.00–0.02, respectively) and for Parkinson’s disease (ERR_pooled at 100 mGy = 0.11; 95% CI: 0.06–0.16); Conclusions: Our findings suggest that adult low-to-moderate IR exposure may have effects on non-cancerous CNS diseases. Further research addressing inherent variation issues is encouraged. Full article

Background: Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease and gender differences have been described on several aspects of PD. In the present commentary, we aimed to collect and discuss the currently available evidence on gender differences in PD regarding biomarkers, genetic factors, motor and non-motor symptoms, therapeutic management (including pharmacological and surgical treatment) as well as preclinical studies. Methods: A systematic literature review was performed by searching the Pubmed and Scopus databases with the search strings “biomarkers”, “deep brain stimulation”, “female”, “gender”, “genetic”, “levodopa”, “men”, “male”, “motor symptoms”, “non-motor symptoms”, “Parkinson disease”, “sex”, “surgery”, and “women”. Results: The present review confirms the existence of differences between men and women in Parkinson Disease, pointing out new information regarding evidence from animal models, genetic factors, biomarkers, clinical features and pharmacological and surgical treatment. Conclusions: The overall goal is to acquire new informations about sex and gender differences in Parkinson Disease, in order to develop tailored intervetions. Full article

Many research methods applied in molecular neuroscience require the collection of hippocampal samples, but a still poorly recognized problem is contamination with the choroid plexus during brain dissection. Because of a distinct pattern of gene expression, its inclusion in brain samples can obscure or even confound conclusions drawn from molecular studies. Therefore, we tested our dissection method designed for removal of tissue contamination using expression of the transthyretin gene (Ttr) as a marker of the choroid plexus. Additionally, we also validated dissection of the entire hippocampus into its dorsal, intermediate and ventral subdivisions using the expression of Trhr and Lct genes as molecular markers of anatomical subdivisions. The PCR analysis showed that Ttr is expressed at a residual level in hippocampal samples that display an mRNA level several hundred lower than the adjacent control tissue colocalized with the choroid plexus. This indicates that the applied method for dissecting the hippocampus from a fresh brain allows for replicable removal of the majority of choroid plexus from hippocampal samples. In turn, differences in expression of Lct and Trhr confirmed the proper dissection of dorsal, intermediate and ventral subdivisions from fresh brain tissue. Therefore, a special emphasis on the removal of tissue contamination and avoidance of tissue distortions makes our protocol especially suitable for molecular experiments performed either on the entire hippocampus or its subdivisions. Full article

Objective: The aim of this study was to evaluate ten exercise interventions (YOGA: yoga training, RT: resistance training, AQU: aquatic training, TAI: Taiji Qigong training, TRD: treadmill training, VR: virtual reality training, DANCE: musical dance training, WKT: walking training, CYC: cycling training, BDJ: Baduanjin Qigong training) on motor function in Parkinson’s disease (PD) patients. Design: Through searching PubMed, Embase, Cochrane Library, Web of Science, and CNKI, only randomized controlled trials (RCTs) were collected to study the effects of the ten exercise interventions on motor function in patients with Parkinson’s disease. The included studies were evaluated for methodological quality by the Cochrane bias risk assessment tool. Results: The RCTs were collected between the earliest available date and April 2022. Sixty RCTs were included and the total sample size used in the study was 2859. The results of the network meta-analysis showed that DANCE can significantly improve patients’ Berg Balance Scale (BBS) (SUCRA = 78.4%); DANCE can significantly decline patients’ Unified Parkinson’s Disease Rating Scale score (UPDRS) (SUCRA = 72.3%) and YOGA can significantly decline patients’ Timed-Up-and-Go score (TUGT) (SUCRA = 78.0%). Conclusion: Based on the network meta-analysis and SUCRA ranking, we can state that dance, yoga, virtual reality training and resistance training offers better advantages than other exercise interventions for patients’ motor function. Full article

Bodily experiences such as the feeling of touch, pain or inner signals of the body are deeply emotional and activate brain networks that mediate their perception and higher-order processing. While the ad hoc perception of bodily signals and their influence on behavior is empirically well studied, there is a knowledge gap on how we store and retrieve bodily experiences that we perceived in the past, and how this influences our everyday life. Here, we explore the hypothesis that negative body memories, that is, negative bodily experiences of the past that are stored in memory and influence behavior, contribute to the development of somatic manifestations of mental health problems including somatic symptoms, traumatic re-experiences or dissociative symptoms. By combining knowledge from the areas of cognitive neuroscience and clinical neuroscience with insights from psychotherapy, we identify Clinical Body Memory (CBM) mechanisms that specify how mental health problems could be driven by corporeal experiences stored in memory. The major argument is that the investigation of the neuronal mechanisms that underlie the storage and retrieval of body memories provides us with empirical access to reduce the negative impact of body memories on mental health. Full article

L-glutamate (L-Glu) is a nonessential amino acid, but an extensively utilised excitatory neurotransmitter with critical roles in normal brain function. Aberrant accumulation of L-Glu has been linked to neurotoxicity and neurodegeneration. To investigate this further, we systematically reviewed the literature to evaluate the effects of L-Glu on neuronal viability linked to the pathogenesis and/or progression of neurodegenerative diseases (NDDs). A search in PubMed, Medline, Embase, and Web of Science Core Collection was conducted to retrieve studies that investigated an association between L-Glu and pathology for five NDDs: Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD). Together, 4060 studies were identified, of which 71 met eligibility criteria. Despite several inadequacies, including small sample size, employment of supraphysiological concentrations, and a range of administration routes, it was concluded that exposure to L-Glu in vitro or in vivo has multiple pathogenic mechanisms that influence neuronal viability. These mechanisms include oxidative stress, reduced antioxidant defence, neuroinflammation, altered neurotransmitter levels, protein accumulations, excitotoxicity, mitochondrial dysfunction, intracellular calcium level changes, and effects on neuronal histology, cognitive function, and animal behaviour. This implies that clinical and epidemiological studies are required to assess the potential neuronal harm arising from excessive intake of exogenous L-Glu. Full article

Mortality of acute coronavirus disease (COVID-19) is higher in men than in women. On the contrary, women experience more long-term consequences of the disease, such as fatigue. In this perspective article, we proposed a model of the potential factors that might contribute to the higher incidence of post-COVID-19 fatigue in women. Specifically, psycho-physiological factors are features that might increase central factors (e.g., inflammation) and result in greater perceptions of fatigue. Furthermore, pre-existing conditions likely play a prominent role. This model offers a framework for researchers and clinicians, and future research is required to validate our proposed model and elucidate all mechanisms of the increased incidence and prevalence of post-COVID-19 fatigue in women. Full article

The standard of care for isocitrate dehydrogenase (IDH)-wildtype glioblastoma (GBM) is maximal resection followed by chemotherapy and radiation. Studies investigating the resection of GBM have primarily focused on the contrast enhancing portion of the tumor on magnetic resonance imaging. Histopathological studies, however, have demonstrated tumor infiltration within peri-tumoral fluid-attenuated inversion recovery (FLAIR) abnormalities, which is often not resected. The histopathology of FLAIR and local recurrence patterns of GBM have prompted interest in the resection of peri-tumoral FLAIR, or FLAIRectomy. To this point, recent studies have suggested a significant survival benefit associated with safe peri-tumoral FLAIR resection. In this review, we discuss the evidence surrounding the composition of peri-tumoral FLAIR, outcomes associated with FLAIRectomy, future directions of the field, and potential implications for patients. Full article

Few data are available regarding the incidence and the evolution of neuropsychiatric manifestations in children with a history of COVID-19. We herein report five consequent cases of pediatric patients with psychiatric and neurological symptoms of long COVID-19. All patients, mainly males, reported asymptomatic-to-mild COVID-19 and underwent home self-isolation. Abnormal movements, anxiety, and emotional dysregulation were the most recurrent symptoms observed from a few weeks to months after the resolution of the acute infection. A later onset was observed in younger patients. Blood tests and brain imaging resulted in negative results in all subjects; pharmacological and cognitive behavioral therapy was set. A multifactorial etiology could be hypothesized in these cases, as a result of a complex interplay between systemic and brain inflammation and environmental stress in vulnerable individuals. Longer follow-up is required to observe the evolution of neuropsychiatric manifestation in the present cohort and other young patients with previous SARS-CoV-2 infection. Full article