Editor’s Choice Articles

Editor’s Choice articles are based on recommendations by the scientific editors of MDPI journals from around the world. Editors select a small number of articles recently published in the journal that they believe will be particularly interesting to readers, or important in the respective research area. The aim is to provide a snapshot of some of the most exciting work published in the various research areas of the journal.

Order results
Result details
Results per page
Select all
Export citation of selected articles as:
12 pages, 561 KiB  
Review
Neuroimaging Techniques as Descriptive and Diagnostic Tools for Infants at Risk for Autism Spectrum Disorder: A Systematic Review
by Maria J. Ayoub, Laura Keegan, Helen Tager-Flusberg and Simone V. Gill
Brain Sci. 2022, 12(5), 602; https://doi.org/10.3390/brainsci12050602 - 05 May 2022
Cited by 7 | Viewed by 2529
Abstract
Autism Spectrum Disorder (ASD) has traditionally been evaluated and diagnosed via behavioral assessments. However, increasing research suggests that neuroimaging as early as infancy can reliably identify structural and functional differences between autistic and non-autistic brains. The current review provides a systematic overview of [...] Read more.
Autism Spectrum Disorder (ASD) has traditionally been evaluated and diagnosed via behavioral assessments. However, increasing research suggests that neuroimaging as early as infancy can reliably identify structural and functional differences between autistic and non-autistic brains. The current review provides a systematic overview of imaging approaches used to identify differences between infants at familial risk and without risk and predictive biomarkers. Two primary themes emerged after reviewing the literature: (1) neuroimaging methods can be used to describe structural and functional differences between infants at risk and infants not at risk for ASD (descriptive), and (2) neuroimaging approaches can be used to predict ASD diagnosis among high-risk infants and developmental outcomes beyond infancy (predicting later diagnosis). Combined, the articles highlighted that several neuroimaging studies have identified a variety of neuroanatomical and neurological differences between infants at high and low risk for ASD, and among those who later receive an ASD diagnosis. Incorporating neuroimaging into ASD evaluations alongside traditional behavioral assessments can provide individuals with earlier diagnosis and earlier access to supportive resources. Full article
(This article belongs to the Special Issue Advances in Neural Basis of Infant Information Processing)
Show Figures

Figure 1

24 pages, 730 KiB  
Opinion
Clinical Manifestations of Body Memories: The Impact of Past Bodily Experiences on Mental Health
by Antje Gentsch and Esther Kuehn
Brain Sci. 2022, 12(5), 594; https://doi.org/10.3390/brainsci12050594 - 03 May 2022
Cited by 11 | Viewed by 5534
Abstract
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 [...] Read more.
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
Show Figures

Figure 1

15 pages, 1531 KiB  
Article
Investigation of Whole and Glandular Saliva as a Biomarker for Alzheimer’s Disease Diagnosis
by Yangyang Cui, Hankun Zhang, Jia Zhu, Zhenhua Liao, Song Wang and Weiqiang Liu
Brain Sci. 2022, 12(5), 595; https://doi.org/10.3390/brainsci12050595 - 03 May 2022
Cited by 9 | Viewed by 1762
Abstract
Salivary Aβ40, Aβ42, t-tau, and p-tau 181 are commonly employed in Alzheimer’s disease (AD) investigations. However, the collection method of these biomarkers can affect their levels. To assess the impact of saliva collection methods on biomarkers in this study, 15 healthy people [...] Read more.
Salivary Aβ40, Aβ42, t-tau, and p-tau 181 are commonly employed in Alzheimer’s disease (AD) investigations. However, the collection method of these biomarkers can affect their levels. To assess the impact of saliva collection methods on biomarkers in this study, 15 healthy people were employed in the morning with six saliva collection methods. The chosen methods were then applied in 30 AD patients and 30 non-AD controls. The levels of salivary biomarkers were calculated by a specific enzyme-linked immunosorbent assay. The receiver operating characteristic was utilized to assess salivary biomarkers in AD patients. The results demonstrated that the highest levels of salivary Aβ40, Aβ42, t-tau, and p-tau were in different saliva collection methods. The correlations between different saliva biomarkers in the same collection method were different. Salivary Aβ40, Aβ42, t-tau, and p-tau had no significant association. Salivary Aβ42 was higher in AD than in non-AD controls. However, p-tau/t-tau and Aβ42/Aβ40 had some relevance. The area under the curve for four biomarkers combined in AD diagnosis was 92.11%. An alternate saliva collection method (e.g., USS in Aβ40, UPS in Aβ42, t-tau, SSS in p-tau 181) was demonstrated in this study. Moreover, combining numerous biomarkers improves AD diagnosis. Full article
Show Figures

Figure 1

11 pages, 500 KiB  
Article
Association between Sleep Quality and Mental Health among Patients at a Post-COVID-19 Recovery Clinic
by Sara Nowakowski, Manasa Kokonda, Rizwana Sultana, Brittany B. Duong, Sarah E. Nagy, Mohammed F. Zaidan, Mirza M. Baig, Bryan V. Grigg, Justin Seashore and Rachel R. Deer
Brain Sci. 2022, 12(5), 586; https://doi.org/10.3390/brainsci12050586 - 30 Apr 2022
Cited by 13 | Viewed by 3768
Abstract
A growing body of research documents the persistence of physical and neuropsychiatric symptoms following the resolution of acute COVID-19 infection. To the best of our knowledge, no published study has examined the interaction between insomnia and mental health. Accordingly, we proposed to examine [...] Read more.
A growing body of research documents the persistence of physical and neuropsychiatric symptoms following the resolution of acute COVID-19 infection. To the best of our knowledge, no published study has examined the interaction between insomnia and mental health. Accordingly, we proposed to examine new diagnoses of insomnia, and referrals to pulmonary and sleep medicine clinics for treatment of sleep disorders, in patients presenting to one post-acute COVID-19 recovery clinic. Additionally, we aimed to examine the relationship between poor sleep quality, depression, anxiety, and post-traumatic stress. Patients presented to the clinic on average 2 months following COVID-19 infection; 51.9% (n = 41) were hospitalized, 11.4% (n = 9) were in the intensive care unit, 2.5% (n = 2) were on a mechanical ventilator, and 38.0% (n = 30) were discharged on oxygen. The most commonly reported symptom was fatigue (88%, n = 70), with worse sleep following a COVID-19 infection reported in 50.6% (n = 40). The mean PSQI score was 9.7 (82.3%, n = 65 with poor sleep quality). The mean GAD-7 score was 8.3 (22.8%, n = 14 with severe depression). The mean PHQ-9 was 10.1 (17.8%, n = 18 with severe anxiety). The mean IES-6 was 2.1 (54.4%, n = 43 with post-traumatic stress). Poor sleep quality was significantly associated with increased severity of depression, anxiety, and post-traumatic stress. Future work should follow patients longitudinally to examine if sleep, fatigue, and mental health symptoms improve over time. Full article
(This article belongs to the Section Behavioral Neuroscience)
Show Figures

Figure 1

43 pages, 2222 KiB  
Systematic Review
Is L-Glutamate Toxic to Neurons and Thereby Contributes to Neuronal Loss and Neurodegeneration? A Systematic Review
by Maryam N. AL-Nasser, Ian R. Mellor and Wayne G. Carter
Brain Sci. 2022, 12(5), 577; https://doi.org/10.3390/brainsci12050577 - 29 Apr 2022
Cited by 24 | Viewed by 4609
Abstract
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 [...] Read more.
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
(This article belongs to the Section Molecular and Cellular Neuroscience)
Show Figures

Graphical abstract

15 pages, 1392 KiB  
Article
The Cost of Imagined Actions in a Reward-Valuation Task
by Manuela Sellitto, Damiano Terenzi, Francesca Starita, Giuseppe di Pellegrino and Simone Battaglia
Brain Sci. 2022, 12(5), 582; https://doi.org/10.3390/brainsci12050582 - 29 Apr 2022
Cited by 9 | Viewed by 2778
Abstract
Growing evidence suggests that humans and other animals assign value to a stimulus based not only on its inherent rewarding properties, but also on the costs of the action required to obtain it, such as the cost of time. Here, we examined whether [...] Read more.
Growing evidence suggests that humans and other animals assign value to a stimulus based not only on its inherent rewarding properties, but also on the costs of the action required to obtain it, such as the cost of time. Here, we examined whether such cost also occurs for mentally simulated actions. Healthy volunteers indicated their subjective value for snack foods while the time to imagine performing the action to obtain the different stimuli was manipulated. In each trial, the picture of one food item and a home position connected through a path were displayed on a computer screen. The path could be either large or thin. Participants first rated the stimulus, and then imagined moving the mouse cursor along the path from the starting position to the food location. They reported the onset and offset of the imagined movements with a button press. Two main results emerged. First, imagery times were significantly longer for the thin than the large path. Second, participants liked significantly less the snack foods associated with the thin path (i.e., with longer imagery time), possibly because the passage of time strictly associated with action imagery discounts the value of the reward. Importantly, such effects were absent in a control group of participants who performed an identical valuation task, except that no action imagery was required. Our findings hint at the idea that imagined actions, like real actions, carry a cost that affects deeply how people assign value to the stimuli in their environment. Full article
Show Figures

Figure 1

14 pages, 1284 KiB  
Article
Literacy Acquisition Trajectories in Bilingual Language Minority Children and Monolingual Peers with Similar or Different SES: A Three-Year Longitudinal Study
by Paola Bonifacci, Ida Carmen Ferrara, Jessica Pedrinazzi, Francesco Terracina and Paola Palladino
Brain Sci. 2022, 12(5), 563; https://doi.org/10.3390/brainsci12050563 - 27 Apr 2022
Cited by 8 | Viewed by 2002
Abstract
Bilingualism and socio-economic status (SES) differentially affect linguistic and cognitive development. However, less evidence has been collected regarding their impact on literacy trajectories. The present longitudinal study evaluated the literacy development of language minority bilingual children (LMBC) and monolingual peers with different SES. [...] Read more.
Bilingualism and socio-economic status (SES) differentially affect linguistic and cognitive development. However, less evidence has been collected regarding their impact on literacy trajectories. The present longitudinal study evaluated the literacy development of language minority bilingual children (LMBC) and monolingual peers with different SES. A group of LMBC with low-SES (n = 18) and monolingual peers with low (n = 18) or high (n = 14) SES were followed from 2nd to 5th grade through a set of tasks assessing decoding (words, nonwords, passage), reading, and listening comprehension, and spelling skills. The results showed that all groups achieved better performances over time in all measures, except listening comprehension. However, low-SES LMBC underperformed in spelling tasks compared to the monolingual groups. In reading comprehension, there was a time*group interaction that showed how low-SES LMBC reached similar performances of low-SES monolinguals in fifth grade, but both groups underperformed compared to the high SES monolingual group. The discussion is focused on the need for research and educational settings to consider the differential impact of bilingualism and SES. Bilingualism seems to be associated with a longer time in developing adequate spelling skills, whereas SES was the primary underpinning of the reading comprehension gap over time. Full article
(This article belongs to the Special Issue Advances in Second Language Learning and Literacy Acquisition)
Show Figures

Figure 1

21 pages, 3699 KiB  
Review
Transcranial Direct Current Stimulation Enhances Cognitive Function in Patients with Mild Cognitive Impairment and Early/Mid Alzheimer’s Disease: A Systematic Review and Meta-Analysis
by Jiajie Chen, Zheng Wang, Qin Chen, Yu Fu and Kai Zheng
Brain Sci. 2022, 12(5), 562; https://doi.org/10.3390/brainsci12050562 - 27 Apr 2022
Cited by 16 | Viewed by 3237
Abstract
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 [...] Read more.
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
(This article belongs to the Section Social Cognitive and Affective Neuroscience)
Show Figures

Figure 1

8 pages, 453 KiB  
Perspective
Potential Factors That Contribute to Post-COVID-19 Fatigue in Women
by Thorsten Rudroff, Craig D. Workman and Andrew D. Bryant
Brain Sci. 2022, 12(5), 556; https://doi.org/10.3390/brainsci12050556 - 26 Apr 2022
Cited by 12 | Viewed by 2444
Abstract
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 [...] Read more.
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
(This article belongs to the Section Systems Neuroscience)
Show Figures

Figure 1

10 pages, 861 KiB  
Article
Fluorescence-Guided Surgery in Glioblastoma: 5-ALA, SF or Both? Differences between Fluorescent Dyes in 99 Consecutive Cases
by Pietro Zeppa, Raffaele De Marco, Matteo Monticelli, Armando Massara, Andrea Bianconi, Giuseppe Di Perna, Stefania Greco Crasto, Fabio Cofano, Antonio Melcarne, Michele Maria Lanotte and Diego Garbossa
Brain Sci. 2022, 12(5), 555; https://doi.org/10.3390/brainsci12050555 - 26 Apr 2022
Cited by 13 | Viewed by 2347
Abstract
Background: Glioblastoma (GBM) is the most common primary brain tumor. The extent of resection (EOR) has been claimed as one of the most important prognostic factors. Fluorescent dyes aid surgeons in detecting a tumor’s borders. 5-aminolevulinic acid (5-ALA) and sodium fluorescein (SF) are [...] Read more.
Background: Glioblastoma (GBM) is the most common primary brain tumor. The extent of resection (EOR) has been claimed as one of the most important prognostic factors. Fluorescent dyes aid surgeons in detecting a tumor’s borders. 5-aminolevulinic acid (5-ALA) and sodium fluorescein (SF) are the most used. Only a few studies have directly compared these two fluorophores. Methods: A single center retrospective analysis of patients treated for GBM in the period between January 2018 and January 2021 was built to find any differences in terms of EOR, Karnofsky Performance Status (KPS), and overall survival (OS) on the use of 5-ALA, SF, or both. Results: Overall, 99 patients affected by isocitrate dehydrogenase (IDH) wild-type Glioblastoma were included. 5-ALA was administered to 40 patients, SF to 44, and both to 15. No statistically significant associations were identified between the fluorophore and EOR (p = 0.783) or postoperative KPS (p = 0.270). Survival analyses did not show a selective advantage for the use of a given fluorophore (p = 0.184), although there appears to be an advantageous trend associated with the concomitant use of both dyes, particularly after stratification by MGMT (p = 0.071). Conclusions: 5-Ala and SF are equally useful in achieving gross total resection of the enhancing tumor volume. The combination of both fluorophores could lead to an OS advantage. Full article
(This article belongs to the Special Issue Frontiers in Neurooncology and Neurosurgery)
Show Figures

Figure 1

10 pages, 675 KiB  
Perspective
FLAIRectomy: Resecting beyond the Contrast Margin for Glioblastoma
by Alexander F. Haddad, Jacob S. Young, Ramin A. Morshed and Mitchel S. Berger
Brain Sci. 2022, 12(5), 544; https://doi.org/10.3390/brainsci12050544 - 25 Apr 2022
Cited by 20 | Viewed by 2712
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue Frontiers in Neurooncology and Neurosurgery)
Show Figures

Figure 1

12 pages, 2999 KiB  
Article
Transfer Learning-Based Model for Diabetic Retinopathy Diagnosis Using Retinal Images
by Muhammad Kashif Jabbar, Jianzhuo Yan, Hongxia Xu, Zaka Ur Rehman and Ayesha Jabbar
Brain Sci. 2022, 12(5), 535; https://doi.org/10.3390/brainsci12050535 - 22 Apr 2022
Cited by 27 | Viewed by 2423
Abstract
Diabetic retinopathy (DR) is a visual obstacle caused by diabetic disease, which forms because of long-standing diabetes mellitus, which damages the retinal blood vessels. This disease is considered one of the principal causes of sightlessness and accounts for more than 158 million cases [...] Read more.
Diabetic retinopathy (DR) is a visual obstacle caused by diabetic disease, which forms because of long-standing diabetes mellitus, which damages the retinal blood vessels. This disease is considered one of the principal causes of sightlessness and accounts for more than 158 million cases all over the world. Since early detection and classification could diminish the visual impairment, it is significant to develop an automated DR diagnosis method. Although deep learning models provide automatic feature extraction and classification, training such models from scratch requires a larger annotated dataset. The availability of annotated training datasets is considered a core issue for implementing deep learning in the classification of medical images. The models based on transfer learning are widely adopted by the researchers to overcome annotated data insufficiency problems and computational overhead. In the proposed study, features are extracted from fundus images using the pre-trained network VGGNet and combined with the concept of transfer learning to improve classification performance. To deal with data insufficiency and unbalancing problems, we employed various data augmentation operations differently on each grade of DR. The results of the experiment indicate that the proposed framework (which is evaluated on the benchmark dataset) outperformed advanced methods in terms of accurateness. Our technique, in combination with handcrafted features, could be used to improve classification accuracy. Full article
(This article belongs to the Special Issue Advances in Seizure Prediction and Detection)
Show Figures

Figure 1

28 pages, 933 KiB  
Review
Inter-Individual Variability in tDCS Effects: A Narrative Review on the Contribution of Stable, Variable, and Contextual Factors
by Alessandra Vergallito, Sarah Feroldi, Alberto Pisoni and Leonor J. Romero Lauro
Brain Sci. 2022, 12(5), 522; https://doi.org/10.3390/brainsci12050522 - 20 Apr 2022
Cited by 31 | Viewed by 3372
Abstract
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 [...] Read more.
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
Show Figures

Figure 1

9 pages, 862 KiB  
Review
Does Olfactory Dysfunction Correlate with Disease Progression in Parkinson’s Disease? A Systematic Review of the Current Literature
by Tommaso Ercoli, Carla Masala, Gianluca Cadeddu, Marcello Mario Mascia, Gianni Orofino, Angelo Fabio Gigante, Paolo Solla, Giovanni Defazio and Lorenzo Rocchi
Brain Sci. 2022, 12(5), 513; https://doi.org/10.3390/brainsci12050513 - 19 Apr 2022
Cited by 16 | Viewed by 2327
Abstract
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 [...] Read more.
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
(This article belongs to the Topic Olfactory Function in Neurodegenerative Disorders)
Show Figures

Figure 1

12 pages, 774 KiB  
Case Report
Neuropsychiatric Disorders in Pediatric Long COVID-19: A Case Series
by Rosa Savino, Anna N. Polito, Giulia Arcidiacono, Mariacristina Poliseno and Sergio Lo Caputo
Brain Sci. 2022, 12(5), 514; https://doi.org/10.3390/brainsci12050514 - 19 Apr 2022
Cited by 13 | Viewed by 3228
Abstract
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 [...] Read more.
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
Show Figures

Figure 1

11 pages, 1809 KiB  
Article
Changes in the Intranetwork and Internetwork Connectivity of the Default Mode Network and Olfactory Network in Patients with COVID-19 and Olfactory Dysfunction
by Hui Zhang, Tom Wai-Hin Chung, Fergus Kai-Chuen Wong, Ivan Fan-Ngai Hung and Henry Ka-Fung Mak
Brain Sci. 2022, 12(4), 511; https://doi.org/10.3390/brainsci12040511 - 18 Apr 2022
Cited by 10 | Viewed by 2581
Abstract
Olfactory dysfunction (OD) is a common symptom in coronavirus disease 2019 (COVID-19) patients. Moreover, many neurological manifestations have been reported in these patients, suggesting central nervous system involvement. The default mode network (DMN) is closely associated with olfactory processing. In this study, we [...] Read more.
Olfactory dysfunction (OD) is a common symptom in coronavirus disease 2019 (COVID-19) patients. Moreover, many neurological manifestations have been reported in these patients, suggesting central nervous system involvement. The default mode network (DMN) is closely associated with olfactory processing. In this study, we investigated the internetwork and intranetwork connectivity of the DMN and the olfactory network (ON) in 13 healthy controls and 22 patients presenting with COVID-19-related OD using independent component analysis and region of interest functional magnetic resonance imaging (fMRI) analysis. There was a significant correlation between the butanol threshold test (BTT) and the intranetwork connectivity in ON. Meanwhile, the COVID-19 patients with OD showed significantly higher intranetwork connectivity in the DMN, as well as higher internetwork connectivity between ON and DMN. However, no significant difference was found between groups in the intranetwork connectivity within ON. We postulate that higher intranetwork functional connectivities compensate for the deficits in olfactory processing and general well-being in COVID-19 patients. Nevertheless, the compensation process in the ON may not be obvious at this stage. Our results suggest that resting-state fMRI is a potentially valuable tool to evaluate neurosensory dysfunction in COVID-19 patients. Full article
(This article belongs to the Section Systems Neuroscience)
Show Figures

Graphical abstract

28 pages, 18716 KiB  
Review
Tumor Microenvironment in Glioma Invasion
by Sho Tamai, Toshiya Ichinose, Taishi Tsutsui, Shingo Tanaka, Farida Garaeva, Hemragul Sabit and Mitsutoshi Nakada
Brain Sci. 2022, 12(4), 505; https://doi.org/10.3390/brainsci12040505 - 15 Apr 2022
Cited by 27 | Viewed by 4635
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue Advance in Glioma Invasion)
Show Figures

Graphical abstract

15 pages, 617 KiB  
Review
The Concept of «Peritumoral Zone» in Diffuse Low-Grade Gliomas: Oncological and Functional Implications for a Connectome-Guided Therapeutic Attitude
by Melissa Silva, Catalina Vivancos and Hugues Duffau
Brain Sci. 2022, 12(4), 504; https://doi.org/10.3390/brainsci12040504 - 15 Apr 2022
Cited by 11 | Viewed by 2637
Abstract
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, [...] Read more.
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
(This article belongs to the Special Issue Frontiers in Neurooncology and Neurosurgery)
Show Figures

Figure 1

20 pages, 1230 KiB  
Review
Molecular Imaging of Central Dopamine in Obesity: A Qualitative Review across Substrates and Radiotracers
by Lieneke Katharina Janssen and Annette Horstmann
Brain Sci. 2022, 12(4), 486; https://doi.org/10.3390/brainsci12040486 - 08 Apr 2022
Cited by 12 | Viewed by 3366
Abstract
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) [...] Read more.
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
(This article belongs to the Special Issue The Brain and Obesity)
Show Figures

Figure 1

22 pages, 2566 KiB  
Article
Intrinsic Shapes of Empathy: Functional Brain Network Topology Encodes Intersubjective Experience and Awareness Traits
by Sjoerd J. H. Ebisch, Andrea Scalabrini, Georg Northoff, Clara Mucci, Maria Rita Sergi, Aristide Saggino, Antonio Aquino, Francesca R. Alparone, Mauro Gianni Perrucci, Vittorio Gallese and Simone Di Plinio
Brain Sci. 2022, 12(4), 477; https://doi.org/10.3390/brainsci12040477 - 05 Apr 2022
Cited by 8 | Viewed by 3714
Abstract
Trait empathy is an essential personality feature in the intricacy of typical social inclinations of individuals. Empathy is likely supported by multilevel neuronal network functioning, whereas local topological properties determine network integrity. In the present functional MRI study (N = 116), we aimed [...] Read more.
Trait empathy is an essential personality feature in the intricacy of typical social inclinations of individuals. Empathy is likely supported by multilevel neuronal network functioning, whereas local topological properties determine network integrity. In the present functional MRI study (N = 116), we aimed to trace empathic traits to the intrinsic brain network architecture. Empathy was conceived as composed of two dimensions within the concept of pre-reflective, intersubjective understanding. Vicarious experience consists of the tendency to resonate with the feelings of other individuals, whereas intuitive understanding refers to a natural awareness of others’ emotional states. Analyses of graph theoretical measures of centrality showed a relationship between the fronto-parietal network and psychometric measures of vicarious experience, whereas intuitive understanding was associated with sensorimotor and subcortical networks. Salience network regions could constitute hubs for information processing underlying both dimensions. The network properties related to empathy dimensions mainly concern inter-network information flow. Moreover, interaction effects implied several sex differences in the relationship between functional network organization and trait empathy. These results reveal that distinct intrinsic topological network features explain individual differences in separate dimensions of intersubjective understanding. The findings could help understand the impact of brain damage or stimulation through alterations of empathy-related network integrity. Full article
Show Figures

Graphical abstract

14 pages, 1546 KiB  
Article
Kappa Free Light Chains in Cerebrospinal Fluid in Inflammatory and Non-Inflammatory Neurological Diseases
by Franz Felix Konen, Philipp Schwenkenbecher, Konstantin Fritz Jendretzky, Stefan Gingele, Torsten Witte, Kurt-Wolfram Sühs, Matthias Grothe, Malte Johannes Hannich, Marie Süße and Thomas Skripuletz
Brain Sci. 2022, 12(4), 475; https://doi.org/10.3390/brainsci12040475 - 03 Apr 2022
Cited by 8 | Viewed by 2032
Abstract
Background: Oligoclonal bands represent intrathecal immunoglobulin G (IgG) synthesis and play an important role in the diagnosis of multiple sclerosis (MS). Kappa free light chains (KFLC) are increasingly recognized as an additional biomarker for intrathecal Ig synthesis. However, there are limited data on [...] Read more.
Background: Oligoclonal bands represent intrathecal immunoglobulin G (IgG) synthesis and play an important role in the diagnosis of multiple sclerosis (MS). Kappa free light chains (KFLC) are increasingly recognized as an additional biomarker for intrathecal Ig synthesis. However, there are limited data on KFLC in neurological diseases other than MS. Methods: This study, conducted at two centers, retrospectively enrolled 346 non-MS patients. A total of 182 patients were diagnosed with non-inflammatory and 84 with inflammatory neurological diseases other than MS. A further 80 patients were classified as symptomatic controls. Intrathecal KFLC production was determined using different approaches: KFLC index, Reiber’s diagram, Presslauer’s exponential curve, and Senel’s linear curve. Results: Matching results of oligoclonal bands and KFLC (Reiber’s diagram) were frequently observed (93%). The Reiber’s diagram for KFLC detected intrathecal KFLC synthesis in an additional 7% of the patient samples investigated (4% non-inflammatory; 3% inflammatory), which was not found by oligoclonal band detection. Conclusions: The determination of both biomarkers (KFLC and oligoclonal bands) is recommended for routine diagnosis and differentiation of non-inflammatory and inflammatory neurological diseases. Due to the high sensitivity and physiological considerations, the assessment of KFLC in the Reiber’s diagram should be preferred to other evaluation methods. Full article
(This article belongs to the Special Issue Neuroinflammation in Neurological Diseases)
Show Figures

Figure 1

12 pages, 494 KiB  
Review
Pathogenesis of Olfactory Disorders in COVID-19
by Laura Ziuzia-Januszewska and Marcin Januszewski
Brain Sci. 2022, 12(4), 449; https://doi.org/10.3390/brainsci12040449 - 27 Mar 2022
Cited by 12 | Viewed by 2511
Abstract
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 [...] Read more.
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
Show Figures

Figure 1

16 pages, 1335 KiB  
Article
Transcranial Pulsed-Current Stimulation versus Transcranial Direct Current Stimulation in Patients with Disorders of Consciousness: A Pilot, Sham-Controlled Cross-Over Double-Blind Study
by Alice Barra, Martin Rosenfelder, Sepehr Mortaheb, Manon Carrière, Geraldine Martens, Yelena G. Bodien, Leon Morales-Quezada, Andreas Bender, Steven Laureys, Aurore Thibaut and Felipe Fregni
Brain Sci. 2022, 12(4), 429; https://doi.org/10.3390/brainsci12040429 - 24 Mar 2022
Cited by 10 | Viewed by 2922
Abstract
Transcranial direct-current stimulation (tDCS) over the prefrontal cortex can improve signs of consciousness in patients in a minimally conscious state. Transcranial pulsed-current stimulation (tPCS) over the mastoids can modulate brain activity and connectivity in healthy controls. This study investigated the feasibility of tPCS [...] Read more.
Transcranial direct-current stimulation (tDCS) over the prefrontal cortex can improve signs of consciousness in patients in a minimally conscious state. Transcranial pulsed-current stimulation (tPCS) over the mastoids can modulate brain activity and connectivity in healthy controls. This study investigated the feasibility of tPCS as a therapeutic tool in patients with disorders of consciousness (DoC) and compared its neurophysiological and behavioral effects with prefrontal tDCS. This pilot study was a randomized, double-blind sham-controlled clinical trial with three sessions: bi-mastoid tPCS, prefrontal tDCS, and sham. Electroencephalography (EEG) and behavioral assessments were collected before and after each stimulation session. Post minus pre differences were compared using Kruskal–Wallis and Wilcoxon signed-rank tests. Twelve patients with DoC were included in the study (eight females, four traumatic brain injury, 50.3 ± 14 y.o., 8.8 ± 10.5 months post-injury). We did not observe any side-effects following tPCS, nor tDCS, and confirmed their feasibility and safety. We did not find a significant effect of the stimulation on EEG nor behavioral outcomes for tPCS. However, consistent with prior findings, our exploratory analyses suggest that tDCS induces behavioral improvements and an increase in theta frontal functional connectivity. Full article
(This article belongs to the Special Issue Emerging Treatments for Patients with Disorders of Consciousness)
Show Figures

Graphical abstract

12 pages, 1257 KiB  
Perspective
Magnetic Resonance Imaging Confirmed Olfactory Bulb Reduction in Long COVID-19: Literature Review and Case Series
by Andrea Frosolini, Daniela Parrino, Cristoforo Fabbris, Francesco Fantin, Ingrid Inches, Sara Invitto, Giacomo Spinato and Cosimo De Filippis
Brain Sci. 2022, 12(4), 430; https://doi.org/10.3390/brainsci12040430 - 24 Mar 2022
Cited by 15 | Viewed by 3403
Abstract
An altered sense of smell and taste was recognized as one of the most characteristic symptoms of coronavirus infection disease (COVID-19). Despite most patients experiencing a complete functional resolution, there is a 21.3% prevalence of persistent alteration at 12 months after infection. To [...] Read more.
An altered sense of smell and taste was recognized as one of the most characteristic symptoms of coronavirus infection disease (COVID-19). Despite most patients experiencing a complete functional resolution, there is a 21.3% prevalence of persistent alteration at 12 months after infection. To date, magnetic resonance imaging (MRI) findings in these patients have been variable and not clearly defined. We aimed to clarify radiological alterations of olfactory pathways in patients with long COVID-19 characterized by olfactory dysfunction. A comprehensive review of the English literature was performed by analyzing relevant papers about this topic. A case series was presented: all patients underwent complete otorhinolaryngology evaluation including the Sniffin’ Sticks battery test. A previous diagnosis of SARS-CoV-2 infection was confirmed by positive swabs. The MRIs were acquired using a 3.0T MR scanner with a standardized protocol for olfactory tract analysis. Images were first analysed by a dedicated neuroradiologist and subsequently reviewed and compared with the previous available MRIs. The review of the literature retrieved 25 studies; most cases of olfactory dysfunction more than 3 months after SARS-CoV-2 infection showed olfactory bulb (OB) reduction. Patients in the personal case series had asymmetry and a reduction in the volume of the OB. This evidence was strengthened by the comparison with a previous MRI, where the OBs were normal. The results preliminarily confirmed OB reduction in cases of long COVID-19 with an altered sense of smell. Further studies are needed to clarify the epidemiology, pathophysiology and prognosis. Full article
(This article belongs to the Special Issue Chemosensory Perception and Chemosensory Cognition)
Show Figures

Figure 1

26 pages, 3271 KiB  
Review
Integrative Hedonic and Homeostatic Food Intake Regulation by the Central Nervous System: Insights from Neuroimaging
by Alejandro Campos, John D. Port and Andres Acosta
Brain Sci. 2022, 12(4), 431; https://doi.org/10.3390/brainsci12040431 - 24 Mar 2022
Cited by 16 | Viewed by 9646
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue The Brain and Obesity)
Show Figures

Figure 1

15 pages, 20465 KiB  
Article
Ultrasonic Deep Brain Neuromodulation in Acute Disorders of Consciousness: A Proof-of-Concept
by Josh A. Cain, Norman M. Spivak, John P. Coetzee, Julia S. Crone, Micah A. Johnson, Evan S. Lutkenhoff, Courtney Real, Manuel Buitrago-Blanco, Paul M. Vespa, Caroline Schnakers and Martin M. Monti
Brain Sci. 2022, 12(4), 428; https://doi.org/10.3390/brainsci12040428 - 23 Mar 2022
Cited by 15 | Viewed by 3210
Abstract
The promotion of recovery in patients who have entered a disorder of consciousness (DOC; e.g., coma or vegetative states) following severe brain injury remains an enduring medical challenge despite an ever-growing scientific understanding of these conditions. Indeed, recent work has consistently implicated altered [...] Read more.
The promotion of recovery in patients who have entered a disorder of consciousness (DOC; e.g., coma or vegetative states) following severe brain injury remains an enduring medical challenge despite an ever-growing scientific understanding of these conditions. Indeed, recent work has consistently implicated altered cortical modulation by deep brain structures (e.g., the thalamus and the basal ganglia) following brain damage in the arising of, and recovery from, DOCs. The (re)emergence of low-intensity focused ultrasound (LIFU) neuromodulation may provide a means to selectively modulate the activity of deep brain structures noninvasively for the study and treatment of DOCs. This technique is unique in its combination of relatively high spatial precision and noninvasive implementation. Given the consistent implication of the thalamus in DOCs and prior results inducing behavioral recovery through invasive thalamic stimulation, here we applied ultrasound to the central thalamus in 11 acute DOC patients, measured behavioral responsiveness before and after sonication, and applied functional MRI during sonication. With respect to behavioral responsiveness, we observed significant recovery in the week following thalamic LIFU compared with baseline. With respect to functional imaging, we found decreased BOLD signals in the frontal cortex and basal ganglia during LIFU compared with baseline. In addition, we also found a relationship between altered connectivity of the sonicated thalamus and the degree of recovery observed post-LIFU. Full article
(This article belongs to the Special Issue Emerging Treatments for Patients with Disorders of Consciousness)
Show Figures

Figure 1

21 pages, 883 KiB  
Article
What Accounts for the Factors of Psychopathology? An Investigation of the Neurocognitive Correlates of Internalising, Externalising, and the p-Factor
by Darren Haywood, Frank D. Baughman, Barbara A. Mullan and Karen R. Heslop
Brain Sci. 2022, 12(4), 421; https://doi.org/10.3390/brainsci12040421 - 22 Mar 2022
Cited by 10 | Viewed by 2306
Abstract
Neurocognitive deficits have been consistently associated with a wide range of psychopathology and are proposed to not only be a consequence of the development of psychopathology but also directly involved in its aetiology. However, there is no clear understanding of what neurocognitive processes [...] Read more.
Neurocognitive deficits have been consistently associated with a wide range of psychopathology and are proposed to not only be a consequence of the development of psychopathology but also directly involved in its aetiology. However, there is no clear understanding of what neurocognitive processes are particularly important to mental health. In this paper, we explored the association between neurocognitive abilities and the factors derived from structural models of psychopathology. Four hundred participants from a representative community sample completed measures of symptomology and substance use, as well as 8 neurocognitive tasks. We found a correlated-factors model, with internalising and externalising as the higher-order factors, and a single-factor model with only the p-factor, to be good fits for the data. Tasks that measured the speed of processing were significantly associated with internalising, externalising, and the p-factor, and accounted for significant amounts of unique variance in the factors after accounting for the common variance of the other tasks. Tasks that measured working memory, shifting, and inhibition were not significantly associated with psychopathology factors. Our findings suggest that neurocognitive abilities may not be differentially associated with psychopathology factors, but that speed of processing is a common correlate of the factors. We emphasise the importance of examining neurocognitive abilities and psychopathology on the individual level. Full article
Show Figures

Figure 1

21 pages, 1171 KiB  
Review
Keeping the Balance: GABAB Receptors in the Developing Brain and Beyond
by Davide Bassetti
Brain Sci. 2022, 12(4), 419; https://doi.org/10.3390/brainsci12040419 - 22 Mar 2022
Cited by 12 | Viewed by 5522
Abstract
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 [...] Read more.
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 GABAB receptors (GABABRs) 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 GABAA receptors. GABABRs 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, GABABRs 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 GABABRs/GABABR-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 GABABR-targeting drugs. Full article
Show Figures

Figure 1

19 pages, 2591 KiB  
Article
It Takes Two: Interpersonal Neural Synchrony Is Increased after Musical Interaction
by Alexander Khalil, Gabriella Musacchia and John Rehner Iversen
Brain Sci. 2022, 12(3), 409; https://doi.org/10.3390/brainsci12030409 - 20 Mar 2022
Cited by 8 | Viewed by 4092
Abstract
Music’s deeply interpersonal nature suggests that music-derived neuroplasticity relates to interpersonal temporal dynamics, or synchrony. Interpersonal neural synchrony (INS) has been found to correlate with increased behavioral synchrony during social interactions and may represent mechanisms that support them. As social interactions often do [...] Read more.
Music’s deeply interpersonal nature suggests that music-derived neuroplasticity relates to interpersonal temporal dynamics, or synchrony. Interpersonal neural synchrony (INS) has been found to correlate with increased behavioral synchrony during social interactions and may represent mechanisms that support them. As social interactions often do not have clearly delineated boundaries, and many start and stop intermittently, we hypothesize that a neural signature of INS may be detectable following an interaction. The present study aimed to investigate this hypothesis using a pre-post paradigm, measuring interbrain phase coherence before and after a cooperative dyadic musical interaction. Ten dyads underwent synchronous electroencephalographic (EEG) recording during silent, non-interactive periods before and after a musical interaction in the form of a cooperative tapping game. Significant post-interaction increases in delta band INS were found in the post-condition and were positively correlated with the duration of the preceding interaction. These findings suggest a mechanism by which social interaction may be efficiently continued after interruption and hold the potential for measuring neuroplastic adaption in longitudinal studies. These findings also support the idea that INS during social interaction represents active mechanisms for maintaining synchrony rather than mere parallel processing of stimuli and motor activity. Full article
(This article belongs to the Special Issue Advances in Music-Related Neuroplasticity: Mechanisms and Medicine)
Show Figures

Figure 1

16 pages, 297 KiB  
Article
The Elephant in the Room: A Cross-Sectional Study on the Stressful Psychological Effects of the COVID-19 Pandemic in Mental Healthcare Workers
by Alessandra Minelli, Rosana Carvalho Silva, Stefano Barlati, Marika Vezzoli, Sara Carletto, Cinzia Isabello, Marco Bortolomasi, Gabriele Nibbio, Jacopo Lisoni, Valentina Menesello, Giulia Perusi, Vivian Accardo, Giacomo Deste and Antonio Vita
Brain Sci. 2022, 12(3), 408; https://doi.org/10.3390/brainsci12030408 - 19 Mar 2022
Cited by 23 | Viewed by 3687
Abstract
Despite extensive research on COVID-19’s impact on healthcare workers, few studies have targeted mental health workers (MHWs) and none have investigated previous traumatic events. We investigated psychological distress in MHWs after the first lockdown in Italy to understand which COVID-19, sociodemographic, and professional [...] Read more.
Despite extensive research on COVID-19’s impact on healthcare workers, few studies have targeted mental health workers (MHWs) and none have investigated previous traumatic events. We investigated psychological distress in MHWs after the first lockdown in Italy to understand which COVID-19, sociodemographic, and professional variables represented greater effects, and the role of previous trauma. The survey included sociodemographic and professional questions, COVID-19 variables, and the questionnaires Life Events Checklist for DSM-5 (LEC-5), Impact of Event Scale—Revised (IES-R), and Depression Anxiety Stress Scales 21 (DASS-21). On the 271 MHWs who completed the survey (73.1% female; mean age 45.37), we obtained significant effects for contagion fear, experience of patients’ death, increased workload, and worse team relationship during the first wave. Nurses were more affected and showed more post-traumatic stress symptoms, assessed by IES-R, and more depressive, anxiety, and stress symptoms, assessed by DASS-21. The strongest risk factors for distress were greater age, professional role, increased workload, worse team relationship, and separation from family members. Previous experience of severe human suffering and unwanted sexual experiences negatively impacted IES-R and DASS-21 scores. Being a psychiatrist or psychologist/psychotherapist and good team relationships were protective factors. Recent but also previous severe stressful events might represent relevant risk factors for distress, reducing resilience skills. Identifying vulnerable factors and professional categories may help in the development of dedicated measures to prevent emotional burden and support psychological health. Highlights: Psychological distress in mental health workers in the COVID-19 pandemic is more frequent in nurses, who experience more depression, anxiety, and post-traumatic stress symptoms. Previous and recent stressful events are risk factors for distress and should guide intervention strategies. Full article
(This article belongs to the Section Psychiatric Diseases)
Show Figures

Graphical abstract

16 pages, 1166 KiB  
Review
Brain Connectivity and Graph Theory Analysis in Alzheimer’s and Parkinson’s Disease: The Contribution of Electrophysiological Techniques
by Francesca Miraglia, Fabrizio Vecchio, Chiara Pappalettera, Lorenzo Nucci, Maria Cotelli, Elda Judica, Florinda Ferreri and Paolo Maria Rossini
Brain Sci. 2022, 12(3), 402; https://doi.org/10.3390/brainsci12030402 - 18 Mar 2022
Cited by 15 | Viewed by 3581
Abstract
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 [...] Read more.
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
Show Figures

Figure 1

14 pages, 703 KiB  
Review
COVID-19 Vaccination and Neurological Manifestations: A Review of Case Reports and Case Series
by Shitiz Sriwastava, Kanika Sharma, Syed Hassan Khalid, Sakhi Bhansali, Ashish K. Shrestha, Mahmoud Elkhooly, Samiksha Srivastava, Erum Khan, Shruti Jaiswal and Sijin Wen
Brain Sci. 2022, 12(3), 407; https://doi.org/10.3390/brainsci12030407 - 18 Mar 2022
Cited by 34 | Viewed by 7099
Abstract
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 [...] Read more.
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
(This article belongs to the Section Neuropharmacology and Neuropathology)
Show Figures

Figure 1

12 pages, 3734 KiB  
Review
Outcomes after Flow Diverter Treatment in Subarachnoid Hemorrhage: A Meta-Analysis and Development of a Clinical Prediction Model (OUTFLOW)
by Michelle F. M. ten Brinck, Viktoria E. Shimanskaya, René Aquarius, Ronald H. M. A. Bartels, Frederick J. A. Meijer, Petra C. Koopmans, Guido de Jong, Ajay K. Wakhloo, Joost de Vries and Hieronymus D. Boogaarts
Brain Sci. 2022, 12(3), 394; https://doi.org/10.3390/brainsci12030394 - 15 Mar 2022
Cited by 7 | Viewed by 2472
Abstract
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 [...] Read more.
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
Show Figures

Figure 1

13 pages, 1094 KiB  
Article
Changes in the Serum Levels of Cytokines: IL-1β, IL-4, IL-8 and IL-10 in Depression with and without Posttraumatic Stress Disorder
by Ewa Ogłodek
Brain Sci. 2022, 12(3), 387; https://doi.org/10.3390/brainsci12030387 - 14 Mar 2022
Cited by 14 | Viewed by 2332
Abstract
Background: Both depressive disorders (DD) and post-traumatic stress disorders (PTSD) are caused by immune system dysfunction. Affected individuals show increased proinflammatory cytokine concentration levels. Also, it has been hypothesized that DD and PTSD might be associated with a generalized proinflammatory cytokine signature. The [...] Read more.
Background: Both depressive disorders (DD) and post-traumatic stress disorders (PTSD) are caused by immune system dysfunction. Affected individuals show increased proinflammatory cytokine concentration levels. Also, it has been hypothesized that DD and PTSD might be associated with a generalized proinflammatory cytokine signature. The study assessed the concentration of IL-1β, IL-4, IL-8 and IL-10 in depression alone and with PTSD. Methods: The study involved 460 participants. Out of them, 420 subjects comprised a study group and 40 subjects comprised a control group. Each study group consisted of 60 patients with mild depression (MD), moderate depression (MOD), severe depression (SeD), MD and PTSD (MD + PTSD), MOD and PTSD (MOD + PTSD), SeD and PTSD (SeD + PTSD), and with PTSD alone. All patients had serum concentration of IL-1β, IL-4, IL-8 and IL-10 measured with ELISA. Results: DD and PTSD are reflected in IL-1β, IL-4, IL-8 and IL-10 concentration levels. It was reported that mean levels of IL-1β, IL-4, IL-8 increase as depression became more severe. A regular decrease in IL-10 concentration levels was noted with the onset and exacerbation of depressive symptoms. Conclusion: The findings might be useful when considering chronic inflammation as a potential target or biomarker in depression and PTSD treatment. Full article
(This article belongs to the Topic Mechanisms and Treatments of Neurodegenerative Diseases)
Show Figures

Figure 1

17 pages, 5668 KiB  
Article
Cytokines and Neurodegeneration in Epileptogenesis
by Pawel Wolinski, Dominika Ksiazek-Winiarek and Andrzej Glabinski
Brain Sci. 2022, 12(3), 380; https://doi.org/10.3390/brainsci12030380 - 12 Mar 2022
Cited by 15 | Viewed by 2152
Abstract
Epilepsy is a common brain disorder characterized by a heterogenous etiology. Its main features are recurrent seizures. Despite many clinical studies, about 30% of cases are refractory to treatment. Recent studies suggested the important role of immune-system elements in its pathogenesis. It was [...] Read more.
Epilepsy is a common brain disorder characterized by a heterogenous etiology. Its main features are recurrent seizures. Despite many clinical studies, about 30% of cases are refractory to treatment. Recent studies suggested the important role of immune-system elements in its pathogenesis. It was suggested that a deregulated inflammatory process may lead to aberrant neural connectivity and the hyperexcitability of the neuronal network. The aim of our study was the analysis of the expression of inflammatory mediators in a mouse model of epilepsy and their impact on the neurodegeneration process located in the brain. We used the KA-induced model of epilepsy in SJL/J mice and performed the analysis of gene expression and protein levels. We observed the upregulation of IL1β and CXCL12 in the early phase of KA-induced epilepsy and elevated levels of CCL5 at a later time point, compared with control animals. The most important result obtained in our study is the elevation of CXCL2 expression at both studied time points and its correlation with the neurodegeneration observed in mouse brain. Increasing experimental and clinical data suggest the influence of peripheral inflammation on epileptogenesis. Thus, studies focused on the molecular markers of neuroinflammation are of great value and may help deepen our knowledge about epilepsy, leading to the discovery of new drugs. Full article
(This article belongs to the Section Psychiatric Diseases)
Show Figures

Figure 1

14 pages, 352 KiB  
Review
Ketamine as a Novel Psychopharmacotherapy for Eating Disorders: Evidence and Future Directions
by Anya Ragnhildstveit, Matthew Slayton, Laura Kate Jackson, Madeline Brendle, Sachin Ahuja, Willis Holle, Claire Moore, Kellie Sollars, Paul Seli and Reid Robison
Brain Sci. 2022, 12(3), 382; https://doi.org/10.3390/brainsci12030382 - 12 Mar 2022
Cited by 14 | Viewed by 6479
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue New Insights in Psychiatric Disorder Psychopharmacology)
14 pages, 1393 KiB  
Article
Opicapone Improves Global Non-Motor Symptoms Burden in Parkinson’s Disease: An Open-Label Prospective Study
by Diego Santos García, Gustavo Fernández Pajarín, Juan Manuel Oropesa-Ruiz, Francisco Escamilla Sevilla, Raúl Rashid Abdul Rahim López and José Guillermo Muñoz Enríquez
Brain Sci. 2022, 12(3), 383; https://doi.org/10.3390/brainsci12030383 - 12 Mar 2022
Cited by 8 | Viewed by 3185
Abstract
Patients with Parkinson’s disease (PD) can improve some non-motor symptoms (NMS) after starting treatment with opicapone. The aim of this study was to analyze the effectiveness of opicapone on global NMS burden in PD. OPEN-PD (Opicapone Effectiveness on Non-motor symptoms in Parkinson’s Disease) [...] Read more.
Patients with Parkinson’s disease (PD) can improve some non-motor symptoms (NMS) after starting treatment with opicapone. The aim of this study was to analyze the effectiveness of opicapone on global NMS burden in PD. OPEN-PD (Opicapone Effectiveness on Non-motor symptoms in Parkinson’s Disease) is a prospective open-label single-arm study conducted in 5 centers from Spain. The primary efficacy outcome was the change from baseline (V0) to the end of the observational period (6 months ± 30 days) (V2) in the Non-Motor Symptoms Scale (NMSS) total score. Different scales were used for analyzing the change in motor, NMS, quality of life (QoL), and disability. Thirty-three patients were included between JUL/2019 and JUN/2021 (age 63.3 ± 7.91; 60.6% males; 7.48 ± 4.22 years from symptoms onset). At 6 months, 30 patients completed the follow-up (90.9%). The NMSS total score was reduced by 27.3% (from 71.67 ± 37.12 at V0 to 52.1 ± 34.76 at V2; Cohen’s effect size = −0.97; p = 0.002). By domains, improvement was observed in sleep/fatigue (−40.1%; p < 0.0001), mood/apathy (−46.6%; p = 0.001), gastrointestinal symptoms (−20.7%; p = 0.029), and miscellaneous (−44.94%; p = 0.021). QoL also improved with a 18.4% reduction in the 39-item Parkinson’s Disease Quality of Life Questionnaire Summary Index (from 26.67 ± 17.61 at V0 to 21.75 ± 14.9 at V2; p = 0.001). A total of 13 adverse events in 11 patients (33.3%) were reported, 1 of which was severe (not related to opicapone). Dyskinesias and nausea were the most frequent (6.1%). Opicapone is well tolerated and improves global NMS burden and QoL in PD patients at 6 months. Full article
Show Figures

Figure 1

21 pages, 8576 KiB  
Systematic Review
Substance Use in the Transgender Population: A Meta-Analysis
by Miriam Cotaina, Marc Peraire, Mireia Boscá, Iván Echeverria, Ana Benito and Gonzalo Haro
Brain Sci. 2022, 12(3), 366; https://doi.org/10.3390/brainsci12030366 - 10 Mar 2022
Cited by 20 | Viewed by 5419
Abstract
(1) Background: This meta-analysis aimed to assess the relationship between identifying as transgender and substance use. (2) Methods: We searched for relevant studies in PubMed, Scopus, the Web of Science, and PsycINFO on 21 July 2021. (3) Results: Twenty studies comparing transgender and [...] Read more.
(1) Background: This meta-analysis aimed to assess the relationship between identifying as transgender and substance use. (2) Methods: We searched for relevant studies in PubMed, Scopus, the Web of Science, and PsycINFO on 21 July 2021. (3) Results: Twenty studies comparing transgender and cisgender people were included in this work, accounting for a total of 2,376,951 participants (18,329 of whom were transgender). These articles included data on current tobacco use, current tobacco use disorder, current alcohol use, current alcohol use disorder, lifetime substance (all) use, current substance use (excluding tobacco and alcohol), current use of specific substances (excluding tobacco and alcohol and including cocaine, amphetamines, methamphetamines, ecstasy, stimulants, heroin, opiates, cannabis, marijuana, LSD, hallucinogens, steroids, inhalants, sedatives, Ritalin or Adderall, diet pills, cold medicine, prescription medications, polysubstance, other club drugs, and other illegal drugs), and current substance use disorder (excluding tobacco and alcohol). We used the ORs and their 95% CIs to state the association between identifying as transgender and those variables. The control reference category used in all cases was cisgender. We employed a random-effects model. Transgender people were more likely to use tobacco (odds ratio (OR) = 1.65; 95% CI [1.37, 1.98]), have used substances throughout their lives (OR = 1.48; 95% CI [1.30, 1.68]), and present current use of specific substances (OR = 1.79; 95% CI [1.54, 2.07]). When current alcohol and substance use in general and tobacco, alcohol, and substance use disorders specifically were considered, the likelihood did not differ from that of cisgender people. (4) Conclusions: The presence of substance use disorders did not differ between transgender and cisgender people. Considering this population as consumers or as addicted may be a prejudice that perpetuates stigma. Nonetheless, transgender people were more likely to use tobacco and other substances, but not alcohol. Hypothetically, this might be an emotional regulation strategy, a maladaptive mechanism for coping with traumatic experiences, or could respond to minority stress, produced by stigma, prejudice, discrimination, and harassment. It is of particular importance to implement policies against discrimination and stigmatisation and to adapt prevention and treatment services so that they are inclusive of the 2SLGBTQIA+ community. Full article
Show Figures

Figure 1

28 pages, 436 KiB  
Review
Cognitive and Physical Intervention in Metals’ Dysfunction and Neurodegeneration
by Anna Jopowicz, Justyna Wiśniowska and Beata Tarnacka
Brain Sci. 2022, 12(3), 345; https://doi.org/10.3390/brainsci12030345 - 03 Mar 2022
Cited by 7 | Viewed by 3976
Abstract
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 [...] Read more.
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
(This article belongs to the Section Environmental Neuroscience)
26 pages, 2448 KiB  
Article
Smo-Shh Agonist Purmorphamine Prevents Neurobehavioral and Neurochemical Defects in 8-OH-DPAT-Induced Experimental Model of Obsessive-Compulsive Disorder
by Ria Gupta, Sidharth Mehan, Pranshul Sethi, Aradhana Prajapati, Abdulrahman Alshammari, Metab Alharbi, Haneen A. Al-Mazroua and Acharan S. Narula
Brain Sci. 2022, 12(3), 342; https://doi.org/10.3390/brainsci12030342 - 02 Mar 2022
Cited by 16 | Viewed by 3432
Abstract
Obsessive-compulsive disorder is a mental disorder characterized by repetitive, unwanted thoughts and behavior due to abnormal neuronal corticostriatal-thalamocortical pathway and other neurochemical changes. Purmorphamine is a smoothened-sonic-hedgehog agonist that has a protective effect against many neurological diseases due to its role in maintaining [...] Read more.
Obsessive-compulsive disorder is a mental disorder characterized by repetitive, unwanted thoughts and behavior due to abnormal neuronal corticostriatal-thalamocortical pathway and other neurochemical changes. Purmorphamine is a smoothened-sonic-hedgehog agonist that has a protective effect against many neurological diseases due to its role in maintaining functional connectivity during CNS development and its anti-inflammatory and antioxidant properties. As part of our current research, we investigated the neuroprotective effects of PUR against behavioral and neurochemical changes in 8-hydroxy-2-(di-n-propylamino)-tetralin-induced obsessive-compulsive disorder in rats. Additionally, the effect of PUR was compared with the standard drug for OCD, i.e., fluvoxamine. The intra-dorsal raphe-nucleus injection of 8-OH-DPAT in rats for seven days significantly showed OCD-like repetitive and compulsive behavior along with increased oxidative stress, inflammation, apoptosis, as well as neurotransmitter imbalance. These alterations were dose-dependently attenuated by long-term purmorphamine treatment at 5 mg/kg and 10 mg/kg i.p. In this study, we assessed the level of various neurochemical parameters in different biological samples, including brain homogenate, blood plasma, and CSF, to check the drug’s effect centrally and peripherally. These effects were comparable to the standard oral treatment withfluvoxamine at 10 mg/kg. However, when fluvoxamine was given in combination with purmorphamine, there was a more significant restoration of these alterations than the individualtreatmentswithfluvoxamine and purmorphamine. All the above findings demonstrate that the neuroprotective effect of purmorphamine in OCD can be strong evidence for developing a new therapeutic target for treating and managing OCD. Full article
(This article belongs to the Special Issue New Insight into Cellular and Molecular Bases of Brain Disorders)
Show Figures

Graphical abstract

14 pages, 799 KiB  
Review
Regulation of Voluntary Physical Activity Behavior: A Review of Evidence Involving Dopaminergic Pathways in the Brain
by Anaissa Ruiz-Tejada, Janet Neisewander and Christos S. Katsanos
Brain Sci. 2022, 12(3), 333; https://doi.org/10.3390/brainsci12030333 - 01 Mar 2022
Cited by 10 | Viewed by 10275
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue The Role of Dopamine in Neural Circuits)
Show Figures

Graphical abstract

23 pages, 4013 KiB  
Article
In a Bilingual Mood: Mood Affects Lexico-Semantic Processing Differently in Native and Non-Native Languages
by Marcin Naranowicz, Katarzyna Jankowiak, Patrycja Kakuba, Katarzyna Bromberek-Dyzman and Guillaume Thierry
Brain Sci. 2022, 12(3), 316; https://doi.org/10.3390/brainsci12030316 - 26 Feb 2022
Cited by 9 | Viewed by 3167
Abstract
Positive and negative moods tend to have differential effects on lexico-semantic processing in the native language (L1). Though accumulating evidence points to dampened sensitivity to affective stimuli in the non-native language (L2), little is known about the effects of positive and negative moods [...] Read more.
Positive and negative moods tend to have differential effects on lexico-semantic processing in the native language (L1). Though accumulating evidence points to dampened sensitivity to affective stimuli in the non-native language (L2), little is known about the effects of positive and negative moods on L2 processing. Here, we show that lexico-semantic processing is differently affected by positive and negative moods only in L1. Unbalanced Polish–English bilinguals made meaningfulness judgments on L1 and L2 sentences during two EEG recording sessions featuring either positive- or negative-mood-inducing films. We observed a reduced N1 (lexical processing) for negative compared to positive mood in L2 only, a reduced N2 (lexico-semantic processing) in negative compared to positive mood in L1 only, a reduced N400 (lexico-semantic processing) for meaningless compared to meaningful L1 sentences in positive mood only, and an enhanced late positive complex (semantic integration and re-analysis) for L2 compared to L1 meaningful sentence in negative mood only. Altogether, these results suggest that positive and negative moods affect lexical, lexico-semantic, and semantic processing differently in L1 and L2. Our observations are consistent with previous accounts of mood-dependent processing and emotion down-regulation observed in bilinguals. Full article
(This article belongs to the Special Issue Cognitive Neuroscience of Cross-Language Interaction in Bilinguals)
Show Figures

Figure 1

12 pages, 2375 KiB  
Article
Caloric Restriction Mimetic 2-Deoxyglucose Reduces Inflammatory Signaling in Human Astrocytes: Implications for Therapeutic Strategies Targeting Neurodegenerative Diseases
by Kaylie-Anna Juliette Vallee and Jerel Adam Fields
Brain Sci. 2022, 12(3), 308; https://doi.org/10.3390/brainsci12030308 - 24 Feb 2022
Cited by 7 | Viewed by 1726
Abstract
Therapeutic interventions are greatly needed for age-related neurodegenerative diseases. Astrocytes regulate many aspects of neuronal function including bioenergetics and synaptic transmission. Reactive astrocytes are implicated in neurodegenerative diseases due to their pro-inflammatory phenotype close association with damaged neurons. Thus, strategies to reduce astrocyte [...] Read more.
Therapeutic interventions are greatly needed for age-related neurodegenerative diseases. Astrocytes regulate many aspects of neuronal function including bioenergetics and synaptic transmission. Reactive astrocytes are implicated in neurodegenerative diseases due to their pro-inflammatory phenotype close association with damaged neurons. Thus, strategies to reduce astrocyte reactivity may support brain health. Caloric restriction and a ketogenic diet limit energy production via glycolysis and promote oxidative phosphorylation, which has gained traction as a strategy to improve brain health. However, it is unknown how caloric restriction affects astrocyte reactivity in the context of neuroinflammation. We investigated how a caloric restriction mimetic and glycolysis inhibitor, 2-deoxyglucose (2-DG), affects interleukin 1β-induced inflammatory gene expression in human astrocytes. Human astrocyte cultures were exposed to 2-DG or vehicle for 24 h and then to recombinant IL-1β for 6 or 24 h to analyze mRNA and protein expression, respectively. Gene expression levels of proinflammatory genes (complement component 3, IL-1β, IL6, and TNFα) were analyzed by real-time PCR, immunoblot, and immunohistochemistry. As expected, IL-1β induced elevated levels of proinflammatory genes. 2-DG reversed this effect at the mRNA and protein levels without inducing cytotoxicity. Collectively, these data suggest that inhibiting glycolysis in human astrocytes reduces IL-1β-induced reactivity. This finding may lead to novel therapeutic strategies to limit inflammation and enhance bioenergetics toward the goal of preventing and treating neurodegenerative diseases. Full article
Show Figures

Figure 1

20 pages, 3897 KiB  
Article
Validation of a Light EEG-Based Measure for Real-Time Stress Monitoring during Realistic Driving
by Nicolina Sciaraffa, Gianluca Di Flumeri, Daniele Germano, Andrea Giorgi, Antonio Di Florio, Gianluca Borghini, Alessia Vozzi, Vincenzo Ronca, Rodrigo Varga, Marteyn van Gasteren, Fabio Babiloni and Pietro Aricò
Brain Sci. 2022, 12(3), 304; https://doi.org/10.3390/brainsci12030304 - 24 Feb 2022
Cited by 21 | Viewed by 3021
Abstract
Driver’s stress affects decision-making and the probability of risk occurrence, and it is therefore a key factor in road safety. This suggests the need for continuous stress monitoring. This work aims at validating a stress neurophysiological measure—a Neurometric—for out-of-the-lab use obtained from lightweight [...] Read more.
Driver’s stress affects decision-making and the probability of risk occurrence, and it is therefore a key factor in road safety. This suggests the need for continuous stress monitoring. This work aims at validating a stress neurophysiological measure—a Neurometric—for out-of-the-lab use obtained from lightweight EEG relying on two wet sensors, in real-time, and without calibration. The Neurometric was tested during a multitasking experiment and validated with a realistic driving simulator. Twenty subjects participated in the experiment, and the resulting stress Neurometric was compared with the Random Forest (RF) model, calibrated by using EEG features and both intra-subject and cross-task approaches. The Neurometric was also compared with a measure based on skin conductance level (SCL), representing one of the physiological parameters investigated in the literature mostly correlated with stress variations. We found that during both multitasking and realistic driving experiments, the Neurometric was able to discriminate between low and high levels of stress with an average Area Under Curve (AUC) value higher than 0.9. Furthermore, the stress Neurometric showed higher AUC and stability than both the SCL measure and the RF calibrated with a cross-task approach. In conclusion, the Neurometric proposed in this work proved to be suitable for out-of-the-lab monitoring of stress levels. Full article
Show Figures

Figure 1

12 pages, 2107 KiB  
Article
Interoceptive Attentiveness Induces Significantly More PFC Activation during a Synchronized Linguistic Task Compared to a Motor Task as Revealed by Functional Near-Infrared Spectroscopy
by Michela Balconi and Laura Angioletti
Brain Sci. 2022, 12(3), 301; https://doi.org/10.3390/brainsci12030301 - 23 Feb 2022
Cited by 8 | Viewed by 2279
Abstract
Currently, there is little understanding of how interoceptive attentiveness (IA) affects brain responses during synchronized cognitive or motor tasks. This pilot study explored the effect of explicit IA manipulation on hemodynamic correlates of simple cognitive tasks implying linguistic or motor synchronization. Eighteen healthy [...] Read more.
Currently, there is little understanding of how interoceptive attentiveness (IA) affects brain responses during synchronized cognitive or motor tasks. This pilot study explored the effect of explicit IA manipulation on hemodynamic correlates of simple cognitive tasks implying linguistic or motor synchronization. Eighteen healthy participants completed two linguistic and motor synchronization tasks during explicit IA and control conditions while oxygenated (O2Hb) and deoxygenated (HHb) hemoglobin variations were recorded by functional Near-Infrared Spectroscopy (fNIRS). The findings suggested that the brain regions associated with sustained attention, such as the right prefrontal cortex (PFC), were more involved when an explicit focus on the breath was induced during the cognitive linguistic task requiring synchronization with a partner, as indicated by increased O2Hb. Interestingly, this effect was not significant for the motor task. In conclusion, for the first time, this pilot research found increased activity in neuroanatomical regions that promote sustained attention, attention reorientation, and synchronization when a joint task is carried out and the person is focusing on their physiological body reactions. Moreover, the results suggested that the benefits of conscious concentration on physiological interoceptive correlates while executing a task demanding synchronization, particularly verbal alignment, may be related to the right PFC. Full article
(This article belongs to the Section Social Cognitive and Affective Neuroscience)
Show Figures

Figure 1

17 pages, 582 KiB  
Review
Pain in Persons with Disorders of Consciousness
by Nathan D. Zasler, Rita Formisano and Marta Aloisi
Brain Sci. 2022, 12(3), 300; https://doi.org/10.3390/brainsci12030300 - 23 Feb 2022
Cited by 11 | Viewed by 5710
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue Emerging Treatments for Patients with Disorders of Consciousness)
Show Figures

Figure 1

13 pages, 1269 KiB  
Article
Dimensions of Tinnitus-Related Distress
by Petra Brueggemann, Wilhelm Mebus, Benjamin Boecking, Nyamaa Amarjargal, Uli Niemann, Myra Spiliopoulou, Christian Dobel, Matthias Rose and Birgit Mazurek
Brain Sci. 2022, 12(2), 275; https://doi.org/10.3390/brainsci12020275 - 16 Feb 2022
Cited by 15 | Viewed by 2669
Abstract
Objectives: (1) To determine which psychosocial aspects predict tinnitus-related distress in a large self-reported dataset of patients with chronic tinnitus, and (2) to identify underlying constructs by means of factor analysis. Methods: A cohort of 1958 patients of the Charité Tinnitus Center, Berlin [...] Read more.
Objectives: (1) To determine which psychosocial aspects predict tinnitus-related distress in a large self-reported dataset of patients with chronic tinnitus, and (2) to identify underlying constructs by means of factor analysis. Methods: A cohort of 1958 patients of the Charité Tinnitus Center, Berlin completed a large questionnaire battery that comprised sociodemographic data, tinnitus-related distress, general psychological stress experience, emotional symptoms, and somatic complaints. To identify a construct of “tinnitus-related distress”, significant predictive items were grouped using factor analysis. Results: For the prediction of tinnitus-related distress (linear regression model with R2 = 0.7), depressive fatigue symptoms (concentration, sleep, rumination, joy decreased), the experience of emotional strain, somatization tendencies (pain experience, doctor contacts), and age appeared to play a role. The factor analysis revealed five factors: “stress”, “pain experience”, “fatigue”, “autonomy”, and low “educational level”. Conclusions: Tinnitus-related distress is predicted by psychological and sociodemographic indices. Relevant factors seem to be depressive exhaustion with somatic expressions such as sleep and concentration problems, somatization, general psychological stress, and reduced activity, in addition to higher age. Full article
Show Figures

Figure 1

18 pages, 17913 KiB  
Article
Semantic Feature Extraction Using SBERT for Dementia Detection
by Yamanki Santander-Cruz, Sebastián Salazar-Colores, Wilfrido Jacobo Paredes-García, Humberto Guendulain-Arenas and Saúl Tovar-Arriaga
Brain Sci. 2022, 12(2), 270; https://doi.org/10.3390/brainsci12020270 - 15 Feb 2022
Cited by 15 | Viewed by 3506
Abstract
Dementia is a neurodegenerative disease that leads to the development of cognitive deficits, such as aphasia, apraxia, and agnosia. It is currently considered one of the most significant major medical problems worldwide, primarily affecting the elderly. This condition gradually impairs the patient’s cognition, [...] Read more.
Dementia is a neurodegenerative disease that leads to the development of cognitive deficits, such as aphasia, apraxia, and agnosia. It is currently considered one of the most significant major medical problems worldwide, primarily affecting the elderly. This condition gradually impairs the patient’s cognition, eventually leading to the inability to perform everyday tasks without assistance. Since dementia is an incurable disease, early detection plays an important role in delaying its progression. Because of this, tools and methods have been developed to help accurately diagnose patients in their early stages. State-of-the-art methods have shown that the use of syntactic-type linguistic features provides a sensitive and noninvasive tool for detecting dementia in its early stages. However, these methods lack relevant semantic information. In this work, we propose a novel methodology, based on the semantic features approach, by using sentence embeddings computed by Siamese BERT networks (SBERT), along with support vector machine (SVM), K-nearest neighbors (KNN), random forest, and an artificial neural network (ANN) as classifiers. Our methodology extracted 17 features that provide demographic, lexical, syntactic, and semantic information from 550 oral production samples of elderly controls and people with Alzheimer’s disease, provided by the DementiaBank Pitt Corpus database. To quantify the relevance of the extracted features for the dementia classification task, we calculated the mutual information score, which demonstrates a dependence between our features and the MMSE score. The experimental classification performance metrics, such as the accuracy, precision, recall, and F1 score (77, 80, 80, and 80%, respectively), validate that our methodology performs better than syntax-based methods and the BERT approach when only the linguistic features are used. Full article
(This article belongs to the Special Issue Early Recognition of Alzheimer´s Disease)
Show Figures

Figure 1

13 pages, 2822 KiB  
Communication
Examining Association of Personality Characteristics and Neuropsychiatric Symptoms in Post-COVID Syndrome
by Cristina Delgado-Alonso, María Valles-Salgado, Alfonso Delgado-Álvarez, Natividad Gómez-Ruiz, Miguel Yus, Carmen Polidura, Carlos Pérez-Izquierdo, Alberto Marcos, María José Gil, Jorge Matías-Guiu and Jordi A. Matias-Guiu
Brain Sci. 2022, 12(2), 265; https://doi.org/10.3390/brainsci12020265 - 14 Feb 2022
Cited by 7 | Viewed by 2899
Abstract
Background: We aimed to evaluate personality traits in patients with post-COVID syndrome, as well as the association with neuropsychiatric symptoms present in this disorder. Methods: The Big Five Structure Inventory was administered to 93 consecutive patients with a diagnosis of post-COVID syndrome as [...] Read more.
Background: We aimed to evaluate personality traits in patients with post-COVID syndrome, as well as the association with neuropsychiatric symptoms present in this disorder. Methods: The Big Five Structure Inventory was administered to 93 consecutive patients with a diagnosis of post-COVID syndrome as defined by the WHO and to demographically matched controls. We also performed a comprehensive evaluation of depression, anxiety, fatigue, sleep quality, cognitive function, and olfactory function. Results: Patients with post-COVID syndrome scored lower for emotional stability, equanimity, positive mood, and self-control. Extraversion, emotional stability, and openness correlated negatively with anxiety and depression levels. Conscientiousness correlated negatively with anxiety. No statistically significant correlations were observed between personality traits and cognitive function, sleep quality, olfactory function, or fatigue. Personality scores explained 36.3% and 41% of the variance in scores on the anxiety and depression scales, respectively. Two personality profiles with lower levels of emotional stability were associated with depression and anxiety. Conclusions: Our study shows higher levels of neuroticism in patients with post-COVID syndrome. Personality traits were predictive of the presence of depression and anxiety, but not cognitive function, sleep quality, or fatigue, in the context of post-COVID syndrome. These findings may have implications for the detection of patients at risk of depression and anxiety in post-COVID syndrome, and for the development of preventive and therapeutic interventions. Full article
Show Figures

Figure 1

34 pages, 1425 KiB  
Review
Domain-General Cognitive Skills in Children with Mathematical Difficulties and Dyscalculia: A Systematic Review of the Literature
by Francesca Agostini, Pierluigi Zoccolotti and Maria Casagrande
Brain Sci. 2022, 12(2), 239; https://doi.org/10.3390/brainsci12020239 - 10 Feb 2022
Cited by 10 | Viewed by 4821
Abstract
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 [...] Read more.
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
Show Figures

Figure 1

Back to TopTop