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Brain Sci., Volume 10, Issue 2 (February 2020) – 70 articles

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Cover Story (view full-size image) Lemur tyrosine-kinase 2 (LMTK2) is implicated in several physiological and pathological processes. [...] Read more.
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Open AccessOpinion
Functional and Dysfunctional Neuroplasticity in Learning to Cope with Stress
Brain Sci. 2020, 10(2), 127; https://doi.org/10.3390/brainsci10020127 - 24 Feb 2020
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Abstract
In this brief review, we present evidence of the primary role of learning-associated plasticity in the development of either adaptive or maladaptive coping strategies. Successful interactions with novel stressors foster plasticity within the neural circuits supporting acquisition, consolidation, retrieval, and extinction of instrumental [...] Read more.
In this brief review, we present evidence of the primary role of learning-associated plasticity in the development of either adaptive or maladaptive coping strategies. Successful interactions with novel stressors foster plasticity within the neural circuits supporting acquisition, consolidation, retrieval, and extinction of instrumental learning leading to development of a rich repertoire of flexible and context-specific adaptive coping responses, whereas prolonged or repeated exposure to inescapable/uncontrollable stressors fosters dysfunctional plasticity within the learning circuits leading to perseverant and inflexible maladaptive coping strategies. Finally, the results collected using an animal model of genotype-specific coping styles indicate the engagement of different molecular networks and the opposite direction of stress effects (reduced vs. enhanced gene expression) in stressed animals, as well as different behavioral alterations, in line with differences in the symptoms profile associated with post-traumatic stress disorder. Full article
(This article belongs to the Special Issue Molecular Regulation of Learning-induced Neuronal Plasticity)
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Open AccessArticle
Streptococcus thermophilus ST285 Alters Pro-Inflammatory to Anti-Inflammatory Cytokine Secretion against Multiple Sclerosis Peptide in Mice
Brain Sci. 2020, 10(2), 126; https://doi.org/10.3390/brainsci10020126 - 23 Feb 2020
Viewed by 154
Abstract
Probiotic bacteria have beneficial effects to the development and maintenance of a healthy microflora that subsequently has health benefits to humans. Some of the health benefits attributed to probiotics have been noted to be via their immune modulatory properties suppressing inflammatory conditions. Hence, [...] Read more.
Probiotic bacteria have beneficial effects to the development and maintenance of a healthy microflora that subsequently has health benefits to humans. Some of the health benefits attributed to probiotics have been noted to be via their immune modulatory properties suppressing inflammatory conditions. Hence, probiotics have become prominent in recent years of investigation with regard to their health benefits. As such, in the current study, we determined the effects of Streptococcus thermophilus to agonist MBP8399 peptide immunized mouse spleen cells. It was noted that Streptococcus thermophilus induced a significant increase in the expression of anti-inflammatory IL-4, IL-5, IL-10 cytokines, and decreased the secretion of pro-inflammatory IL-1β and IFN-γ Regular consumption of Streptococcus thermophilus may therefore be beneficial in the management and treatment of autoimmune diseases such as multiple sclerosis. Full article
(This article belongs to the Special Issue Advances in Multiple Sclerosis Research)
Open AccessEditorial
Could Transcranial Direct Current Stimulation Join the Therapeutic Armamentarium in Obsessive-Compulsive Disorder?
Brain Sci. 2020, 10(2), 125; https://doi.org/10.3390/brainsci10020125 - 23 Feb 2020
Viewed by 249
Abstract
Obsessive-compulsive disorder (OCD) is a mental disorder that can affect around 1–3% of individuals [...] Full article
(This article belongs to the Section Neural Engineering)
Open AccessArticle
Evaluating Preschool Visual Attentional Selective-Set: Preliminary ERP Modeling and Simulation of Target Enhancement Homology
Brain Sci. 2020, 10(2), 124; https://doi.org/10.3390/brainsci10020124 - 22 Feb 2020
Viewed by 208
Abstract
We reanalyzed, modeled and simulated Event-Related Potential (ERP) data from 13 healthy children (Mean age = 5.12, Standard Deviation = 0.75) during a computerized visual sustained target detection task. Extending an ERP-based ACT–R (Adaptive Control of Thought–Rational) neurocognitive modeling approach, we tested whether [...] Read more.
We reanalyzed, modeled and simulated Event-Related Potential (ERP) data from 13 healthy children (Mean age = 5.12, Standard Deviation = 0.75) during a computerized visual sustained target detection task. Extending an ERP-based ACT–R (Adaptive Control of Thought–Rational) neurocognitive modeling approach, we tested whether visual sustained selective-set attention in preschool children involves the enhancement of neural response to targets, and it shows key adult-like features (neurofunctional homology). Blinded automatic peaks analysis was conducted on vincentized binned grand ERP averages. Time-course and distribution of scalp activity were detailed through topographic mapping and paths analysis. Reaction times and accuracy were also measured. Adult Magnetic Resonance Imaging-based mapping using ACT–R dipole source modeling and electric-field spiking simulation provided very good fit with the actual ERP data (R2 > 0.70). In most electrodes, between 50 and 400 ms, ERPs concurrent with target presentation were enhanced relative to distractor, without manual response confounds. Triangulation of peak analysis, ACT–R modeling and simulation for the entire ERP epochs up to the moment of manual response (~700 ms, on average) suggested converging evidence of distinct but interacting processes of enhancement and planning for response release/inhibition, respectively. The latter involved functions and structures consistent with adult ERP activity which might correspond to a large-scale network, implicating Dorsal and Ventral Attentional Networks, corticostriatal loops, and subcortical hubs connected to prefrontal cortex top-down working memory executive control. Although preliminary, the present approach suggests novel directions for further tests and falsifiable hypotheses on the origins and development of visual selective attention and their ERP correlates. Full article
(This article belongs to the Special Issue ERP and EEG Markers of Brain Visual Attentional Processing)
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Open AccessArticle
Distinct Effects of Stereotactically Injected Human Cerebrospinal Fluid Containing Glutamic Acid Decarboxylase Antibodies into the Hippocampus of Rats on the Development of Spontaneous Epileptic Activity
Brain Sci. 2020, 10(2), 123; https://doi.org/10.3390/brainsci10020123 - 22 Feb 2020
Viewed by 122
Abstract
Background: The conversion of glutamic acid into γ-aminobutyric acid (GABA) is catalyzed by the glutamic acid decarboxylase (GAD). Antibodies against this enzyme have been described in neurological disorders, but the pathophysiological role of these antibodies is still poorly understood. We hypothesized that [...] Read more.
Background: The conversion of glutamic acid into γ-aminobutyric acid (GABA) is catalyzed by the glutamic acid decarboxylase (GAD). Antibodies against this enzyme have been described in neurological disorders, but the pathophysiological role of these antibodies is still poorly understood. We hypothesized that anti-GAD autoantibodies could diminish the GABA content in the slice and facilitate epileptic activity. Methods: Cerebrospinal fluids (CSF) from two patients containing anti-GAD (A and B) were injected into the rat hippocampus in vivo. Hippocampal slices were prepared for electrophysiological field potential recordings in order to record recurrent epileptic discharges (REDs) in the CA1 region induced by the removal of Mg2+ and/or by adding gabazine. As control groups, we injected an anti-GAD-negative human CSF or saline solution, and we used non-operated naive animals. Results: RED frequencies were significantly higher in the Mg2+-free solution than in the gabazine-containing solution. The average frequency of REDs in the last 10 min and the average duration of REDs in the last 5 min did not show significant differences between the anti-GAD-B-treated and the control slices, but in the Mg2+-free solution, anti-GAD-A had significantly higher epileptic activity than anti-GAD-B. Conclusions: These results indicate that anti-GAD has distinct effects on the development of spontaneous epileptic activity. Full article
(This article belongs to the Special Issue Synaptic Changes in Epilepsy)
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Open AccessCommentary
Enhancing α-secretase Processing for Alzheimer’s Disease—A View on SFRP1
Brain Sci. 2020, 10(2), 122; https://doi.org/10.3390/brainsci10020122 - 22 Feb 2020
Viewed by 120
Abstract
Amyloid β (Aβ) peptides generated via sequential β- and γ-secretase processing of the amyloid precursor protein (APP) are major etiopathological agents of Alzheimer’s disease (AD). However, an initial APP cleavage by an α-secretase, such as the a disintegrin and metalloproteinase domain-containing protein ADAM10, [...] Read more.
Amyloid β (Aβ) peptides generated via sequential β- and γ-secretase processing of the amyloid precursor protein (APP) are major etiopathological agents of Alzheimer’s disease (AD). However, an initial APP cleavage by an α-secretase, such as the a disintegrin and metalloproteinase domain-containing protein ADAM10, precludes β-secretase cleavage and leads to APP processing that does not produce Aβ. The latter appears to underlie the disease symptom-attenuating effects of a multitude of experimental therapeutics in AD animal models. Recent work has indicated that an endogenous inhibitor of ADAM10, secreted-frizzled-related protein 1 (SFRP1), is elevated in human AD brains and associated with amyloid plaques in mouse AD models. Importantly, genetic or functional attenuation of SFRP1 lowered Aβ accumulation and improved AD-related histopathological and neurological traits. Given SFRP1′s well-known activity in attenuating Wnt signaling, which is also commonly impaired in AD, SFRP1 appears to be a promising therapeutic target for AD. This idea, however, needs to be addressed with care because of cancer enhancement potentials resulting from a systemic loss of SFRP1 activity, as well as an upregulation of ADAM10 activity. In this focused review, I shall discuss α-secretase-effected APP processing in AD with a focus on SFRP1, and explore the contrasting perspectives arising from the recent findings. Full article
(This article belongs to the Special Issue Neuropathology of Alzheimer’s Disease)
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Open AccessEditorial
ABCA7—A Member of the ABC Transporter Family in Healthy and Ailing Brain
Brain Sci. 2020, 10(2), 121; https://doi.org/10.3390/brainsci10020121 - 22 Feb 2020
Viewed by 157
Abstract
Identification of genetic markers of a human disease, which is generally sporadic, may become an essential tool for the investigation of its molecular mechanisms. The role of ABCA7 in Alzheimer’s disease (AD) was discovered less than ten years ago when meta-analyses provided evidence [...] Read more.
Identification of genetic markers of a human disease, which is generally sporadic, may become an essential tool for the investigation of its molecular mechanisms. The role of ABCA7 in Alzheimer’s disease (AD) was discovered less than ten years ago when meta-analyses provided evidence that rs3764650 is a new AD susceptibility locus. Recent research advances in this locus and new evidence regarding ABCA7 contribution to the AD pathogenesis brought a new understanding of the underlying mechanisms of this disorder. An interesting, up-to-date review article "ABCA7 and Pathogenic Pathways of Alzheimer’s Disease" by Aikawa et al. (2018), outlines the ABCA7 role in AD and summarizes new findings in this exciting area. ABC transporters or ATP-binding cassette transporters are a superfamily of proteins belonging to a cell transport system. Currently, members of the family are the focus of attention because of their central role in drug pharmacokinetics. Two recent findings are the reason why much attention is drawn to the ABCA7 family. First, is the biochemical data showing a role of ABCA7 in amyloid pathology. Second, genetic data identifying ABCA7 gene variants as loci responsible for the late-onset AD. These results point to the ABCA7 as a significant new contributor to the pathogenesis of AD. Full article
Open AccessArticle
Behavioral and Neuropsychological Evaluation of Executive Functions in Children with Autism Spectrum Disorder in the Gulf Region
Brain Sci. 2020, 10(2), 120; https://doi.org/10.3390/brainsci10020120 - 22 Feb 2020
Viewed by 136
Abstract
This study examined the executive functioning abilities and development profiles of children with autism spectrum disorder (ASD). The participants were 119 children with ASD and 30 typically developing children (age range: 6–12 years) who were recruited from three Gulf states. The findings revealed [...] Read more.
This study examined the executive functioning abilities and development profiles of children with autism spectrum disorder (ASD). The participants were 119 children with ASD and 30 typically developing children (age range: 6–12 years) who were recruited from three Gulf states. The findings revealed executive functioning deficits in the ASD population when compared to the normative data or to those children without ASD. However, not all the forms of executive functioning were found to be impaired. Age-related differences in the patterns of performance on the utilized measures of executive functioning were also identified. The overall findings provide valuable information regarding the different components of the executive functions, which may prove useful in relation to the development of assessment protocols for ASD. Full article
Open AccessReview
Management of Neuroinflammatory Responses to AAV-Mediated Gene Therapies for Neurodegenerative Diseases
Brain Sci. 2020, 10(2), 119; https://doi.org/10.3390/brainsci10020119 - 22 Feb 2020
Viewed by 185
Abstract
Recently, adeno-associated virus (AAV)-mediated gene therapies have attracted clinical interest for treating neurodegenerative diseases including spinal muscular atrophy (SMA), Canavan disease (CD), Parkinson’s disease (PD), and Friedreich’s ataxia (FA). The influx of clinical findings led to the first approved gene therapy for neurodegenerative [...] Read more.
Recently, adeno-associated virus (AAV)-mediated gene therapies have attracted clinical interest for treating neurodegenerative diseases including spinal muscular atrophy (SMA), Canavan disease (CD), Parkinson’s disease (PD), and Friedreich’s ataxia (FA). The influx of clinical findings led to the first approved gene therapy for neurodegenerative disorders in 2019 and highlighted new safety concerns for patients. Large doses of systemically administered AAV stimulate host immune responses, resulting in anti-capsid and anti-transgene immunity with implications for transgene expression, treatment longevity, and patient safety. Delivering lower doses directly to the central nervous system (CNS) is a promising alternative, resulting in higher transgene expression with decreased immune responses. However, neuroinflammatory responses after CNS-targeted delivery of AAV are a critical concern. Reported signs of AAV-associated neuroinflammation in preclinical studies include dorsal root ganglion (DRG) and spinal cord pathology with mononuclear cell infiltration. In this review, we discuss ways to manage neuroinflammation, including choice of AAV capsid serotypes, CNS-targeting routes of delivery, genetic modifications to the vector and/or transgene, and adding immunosuppressive strategies to clinical protocols. As additional gene therapies for neurodegenerative diseases enter clinics, tracking biomarkers of neuroinflammation will be important for understanding the impact immune reactions can have on treatment safety and efficacy. Full article
(This article belongs to the Special Issue Gene Therapy for Neurodegenerative Diseases)
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Open AccessReview
Brain Tumor Analysis Empowered with Deep Learning: A Review, Taxonomy, and Future Challenges
Brain Sci. 2020, 10(2), 118; https://doi.org/10.3390/brainsci10020118 - 22 Feb 2020
Viewed by 154
Abstract
Deep Learning (DL) algorithms enabled computational models consist of multiple processing layers that represent data with multiple levels of abstraction. In recent years, usage of deep learning is rapidly proliferating in almost every domain, especially in medical image processing, medical image analysis, and [...] Read more.
Deep Learning (DL) algorithms enabled computational models consist of multiple processing layers that represent data with multiple levels of abstraction. In recent years, usage of deep learning is rapidly proliferating in almost every domain, especially in medical image processing, medical image analysis, and bioinformatics. Consequently, deep learning has dramatically changed and improved the means of recognition, prediction, and diagnosis effectively in numerous areas of healthcare such as pathology, brain tumor, lung cancer, abdomen, cardiac, and retina. Considering the wide range of applications of deep learning, the objective of this article is to review major deep learning concepts pertinent to brain tumor analysis (e.g., segmentation, classification, prediction, evaluation.). A review conducted by summarizing a large number of scientific contributions to the field (i.e., deep learning in brain tumor analysis) is presented in this study. A coherent taxonomy of research landscape from the literature has also been mapped, and the major aspects of this emerging field have been discussed and analyzed. A critical discussion section to show the limitations of deep learning techniques has been included at the end to elaborate open research challenges and directions for future work in this emergent area. Full article
(This article belongs to the collection Collection on Clinical Neuroscience)
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Open AccessArticle
Assessing the Role of Cannabis Use on Cortical Surface Structure in Adolescents and Young Adults: Exploring Gender and Aerobic Fitness as Potential Moderators
Brain Sci. 2020, 10(2), 117; https://doi.org/10.3390/brainsci10020117 - 22 Feb 2020
Viewed by 108
Abstract
Cannabis use in adolescents and young adults is linked with aberrant brain structure, although findings to date are inconsistent. We examined whether aerobic fitness moderated the effects of cannabis on cortical surface structure and whether gender may play a moderating role. Seventy-four adolescents [...] Read more.
Cannabis use in adolescents and young adults is linked with aberrant brain structure, although findings to date are inconsistent. We examined whether aerobic fitness moderated the effects of cannabis on cortical surface structure and whether gender may play a moderating role. Seventy-four adolescents and young adults completed three-weeks of monitored abstinence, aerobic fitness testing, and structural magnetic resonance imaging (sMRI). Whole-sample linear regressions examined the effects of gender, VO2 max, cannabis use, and their interactions on the surface area (SA) and local gyrification index (LGI). Cannabis use was associated with greater cuneus SA. Gender-by-cannabis predicted precuneus and frontal SA, and precentral, supramarginal, and frontal LGI; female cannabis users demonstrated greater LGI, whereas male cannabis users demonstrated decreased LGI compared to non-users. Aerobic fitness was positively associated with various SA and LGI regions. Cannabis-by-aerobic fitness predicted cuneus SA and occipital LGI. These findings demonstrate that aerobic fitness moderates the impact of cannabis on cortical surface structure, and gender differences are evident. These moderating factors may help explain inconsistencies in the literature and warrant further investigation. Present findings and aerobic fitness literature jointly suggest aerobic intervention may be a low-cost avenue for improving cortical surface structure, although the impact may be gender-specific. Full article
(This article belongs to the Special Issue Cannabis: Neuropsychiatry and Its Effects on Brain and Behavior)
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Open AccessArticle
Image Segmentation of Brain MRI Based on LTriDP and Superpixels of Improved SLIC
Brain Sci. 2020, 10(2), 116; https://doi.org/10.3390/brainsci10020116 - 20 Feb 2020
Viewed by 179
Abstract
Non-uniform gray distribution and blurred edges often result in bias during the superpixel segmentation of medical images of magnetic resonance imaging (MRI). To this end, we propose a novel superpixel segmentation algorithm by integrating texture features and improved simple linear iterative clustering (SLIC). [...] Read more.
Non-uniform gray distribution and blurred edges often result in bias during the superpixel segmentation of medical images of magnetic resonance imaging (MRI). To this end, we propose a novel superpixel segmentation algorithm by integrating texture features and improved simple linear iterative clustering (SLIC). First, a 3D histogram reconstruction model is used to reconstruct the input image, which is further enhanced by gamma transformation. Next, the local tri-directional pattern descriptor is used to extract texture features of the image; this is followed by an improved SLIC superpixel segmentation. Finally, a novel clustering-center updating rule is proposed, using pixels with gray difference with original clustering centers smaller than a predefined threshold. The experiments on the Whole Brain Atlas (WBA) image database showed that, compared to existing state-of-the-art methods, our superpixel segmentation algorithm generated significantly more uniform superpixels, and demonstrated the performance accuracy of the superpixel segmentation in both fuzzy boundaries and fuzzy regions. Full article
(This article belongs to the Special Issue Human Brain Dynamics: Latest Advances and Prospects)
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Open AccessArticle
Random Forest Classification of Alcohol Use Disorder Using fMRI Functional Connectivity, Neuropsychological Functioning, and Impulsivity Measures
Brain Sci. 2020, 10(2), 115; https://doi.org/10.3390/brainsci10020115 - 20 Feb 2020
Viewed by 143
Abstract
Individuals with alcohol use disorder (AUD) are known to manifest a variety of neurocognitive impairments that can be attributed to alterations in specific brain networks. The current study aims to identify specific features of brain connectivity, neuropsychological performance, and impulsivity traits that can [...] Read more.
Individuals with alcohol use disorder (AUD) are known to manifest a variety of neurocognitive impairments that can be attributed to alterations in specific brain networks. The current study aims to identify specific features of brain connectivity, neuropsychological performance, and impulsivity traits that can classify adult males with AUD (n = 30) from healthy controls (CTL, n = 30) using the Random Forest (RF) classification method. The predictor variables were: (i) fMRI-based within-network functional connectivity (FC) of the Default Mode Network (DMN), (ii) neuropsychological scores from the Tower of London Test (TOLT), and the Visual Span Test (VST), and (iii) impulsivity factors from the Barratt Impulsiveness Scale (BIS). The RF model, with a classification accuracy of 76.67%, identified fourteen DMN connections, two neuropsychological variables (memory span and total correct scores of the forward condition of the VST), and all impulsivity factors as significantly important for classifying participants into either the AUD or CTL group. Specifically, the AUD group manifested hyperconnectivity across the bilateral anterior cingulate cortex and the prefrontal cortex as well as between the bilateral posterior cingulate cortex and the left inferior parietal lobule, while showing hypoconnectivity in long-range anterior–posterior and interhemispheric long-range connections. Individuals with AUD also showed poorer memory performance and increased impulsivity compared to CTL individuals. Furthermore, there were significant associations among FC, impulsivity, neuropsychological performance, and AUD status. These results confirm the previous findings that alterations in specific brain networks coupled with poor neuropsychological functioning and heightened impulsivity may characterize individuals with AUD, who can be efficiently identified using classification algorithms such as Random Forest. Full article
(This article belongs to the Special Issue Recent Advances in Human Brain Connectivity)
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Open AccessArticle
Brain Processing of Complex Geometric Forms in a Visual Memory Task Increases P2 Amplitude
Brain Sci. 2020, 10(2), 114; https://doi.org/10.3390/brainsci10020114 - 20 Feb 2020
Viewed by 143
Abstract
We study the cognitive processing of visual working memory in three different conditions of memory load and configuration change. Altering this features has been shown to alter the brain’s processing in memory tasks. Most studies dealing with this issue have used the verbal-phonological [...] Read more.
We study the cognitive processing of visual working memory in three different conditions of memory load and configuration change. Altering this features has been shown to alter the brain’s processing in memory tasks. Most studies dealing with this issue have used the verbal-phonological modality. We use complex geometric polygons to assess visual working memory in a modified change detection task. Three different types of backgrounds were used to manipulate memory loading and 18 complex geometric polygons to manipulate stimuli configuration. The goal of our study was to test whether the memory load and configuration affect the correct-recall ratios. We expected that increasing visual items loading and changing configuration of items would induce differences in working memory performance. Brain activity related to the task was assessed through event-related potentials (ERP), during the test phase of each trial. Our results showed that visual items loading and changing of item configuration affect working memory on test phase on ERP component P2, but does not affect performance. However frontal related ERP component—P3—was minimally affected by visual memory loading or configuration changing, supporting that working memory is related to a filtering processing in posterior brain regions. Full article
(This article belongs to the collection Collection on Cognitive Neuroscience)
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Open AccessArticle
Electrophysiological Differentiation of the Effects of Stress and Accent on Lexical Integration in Highly Fluent Bilinguals
Brain Sci. 2020, 10(2), 113; https://doi.org/10.3390/brainsci10020113 - 20 Feb 2020
Viewed by 126
Abstract
Individuals who acquire a second language (L2) after infancy often retain features of their native language (L1) accent. Cross-language priming studies have shown negative effects of L1 accent on L2 comprehension, but the role of specific speech features, such as lexical stress, is [...] Read more.
Individuals who acquire a second language (L2) after infancy often retain features of their native language (L1) accent. Cross-language priming studies have shown negative effects of L1 accent on L2 comprehension, but the role of specific speech features, such as lexical stress, is mostly unknown. Here, we investigate whether lexical stress and accent differently modulate semantic processing and cross-language lexical activation in Welsh–English bilinguals, given that English and Welsh differ substantially in terms of stress realisation. In an L2 cross-modal priming paradigm, we manipulated the stress pattern and accent of spoken primes, whilst participants made semantic relatedness judgments on visual word targets. Event-related brain potentials revealed a main effect of stress on target integration, such that stimuli with stress patterns compatible with either the L1 or L2 required less processing effort than stimuli with stress incompatible with both Welsh and English. An independent cross-language phonological overlap manipulation revealed an interaction between accent and L1 access. Interestingly, although it increased processing effort, incorrect stress did not significantly modulate semantic priming effects or covert access to L1 phonological representations. Our results are consistent with the concept of language-specific stress templates, and suggest that accent and lexical stress affect speech comprehension mechanisms differentially. Full article
(This article belongs to the Special Issue Cognitive Neuroscience of Cross-Language Interaction in Bilinguals)
Open AccessArticle
Hyperarousal Is Associated with Socioemotional Processing in Individuals with Insomnia Symptoms and Good Sleepers
Brain Sci. 2020, 10(2), 112; https://doi.org/10.3390/brainsci10020112 - 20 Feb 2020
Viewed by 162
Abstract
Despite complaints of difficulties in waking socioemotional functioning by individuals with insomnia, only a few studies have investigated emotion processing performance in this group. Additionally, the role of sleep in socioemotional processing has not been investigated extensively nor using quantitative measures of sleep. [...] Read more.
Despite complaints of difficulties in waking socioemotional functioning by individuals with insomnia, only a few studies have investigated emotion processing performance in this group. Additionally, the role of sleep in socioemotional processing has not been investigated extensively nor using quantitative measures of sleep. Individuals with insomnia symptoms (n = 14) and healthy good sleepers (n = 15) completed two nights of at-home polysomnography, followed by an afternoon of in-lab performance testing on tasks measuring the processing of emotional facial expressions. The insomnia group self-reported less total sleep time, but no other group differences in sleep or task performance were observed. Greater beta EEG power throughout the night was associated with higher intensity ratings of happy, fearful and sad faces for individuals with insomnia, yet blunted sensitivity and lower accuracy for good sleepers. Thus, the presence of hyperarousal differentially impacted socioemotional processing of faces in individuals with insomnia symptoms and good sleepers. Full article
(This article belongs to the Special Issue Insomnia: Beyond Hyperarousal)
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Open AccessArticle
Mindfulness and Psychological Flexibility are Inversely Associated with Caregiver Burden in Parkinson’s Disease
Brain Sci. 2020, 10(2), 111; https://doi.org/10.3390/brainsci10020111 - 20 Feb 2020
Viewed by 177
Abstract
Parkinson’s disease (PD) is a neurodegenerative movement disorder with progressive
impairments in activities of daily living. With disease progression, people with PD (PwP) need
more help and care from their spouses or professional caregivers. Identifying factors that help
caregivers to cope with their [...] Read more.
Parkinson’s disease (PD) is a neurodegenerative movement disorder with progressive
impairments in activities of daily living. With disease progression, people with PD (PwP) need
more help and care from their spouses or professional caregivers. Identifying factors that help
caregivers to cope with their burden is needed to frame future interventions for PwP caregivers.
Mindfulness and psychological flexibility might be factors contributing to resilience against the
burden of giving care. In this cross‐sectional questionnaire‐based study, 118 PwP and their
respective primary caregivers were included. Caregivers reported moderate burden and only mild
depressive symptoms. Mindfulness measured by the Mindfulness Attention and Awareness scale
(p 0.003) and psychological flexibility measured by Acceptance and Actions Questionnaire II (p
0.001) correlated negatively with caregiver burden. Data from this study indicate mindfulness and
psychological flexibility are factors contributing to resilience against caregiver burden. Future
interventions to reduce burden in PwP caregivers might be improved by the inclusion of
mindfulness training programs. Full article
(This article belongs to the collection Collection on Clinical Neuroscience)
Open AccessArticle
Traumatic Brain Injury Patients Mortality and Serum Total Antioxidant Capacity
Brain Sci. 2020, 10(2), 110; https://doi.org/10.3390/brainsci10020110 - 18 Feb 2020
Viewed by 170
Abstract
Objective: Oxidation is involved in secondary brain injury after traumatic brain injury (TBI). Increased concentrations of total antioxidant capacity (TAC) in blood at the time of admission for TBI have been found in non-surviving patients. The main objective of this study was to [...] Read more.
Objective: Oxidation is involved in secondary brain injury after traumatic brain injury (TBI). Increased concentrations of total antioxidant capacity (TAC) in blood at the time of admission for TBI have been found in non-surviving patients. The main objective of this study was to determine the role of serum TAC levels at any time during the first week of TBI for the prediction of early mortality. Methods: Isolated (<10 points in non-cranial aspects of Injury Severity Score) and severe (<9 points in Glasgow Coma Scale) TBI patients were included. Serum TAC concentrations at days 1, 4, and 8 of TBI were determined. The end-point study was 30-day mortality. Results: Higher serum TAC levels at days 1 (p < 0.001), 4 (p < 0.001), and 8 (p = 0.002) of TBI were found in non-surviving (n = 34) than in surviving patients (n = 90). The area under curve (95% Confidence Interval) for prediction of 30-day mortality by serum TAC concentrations at days 1, 4, and 8 of TBI were 0.79 (0.71–0.86; p < 0.001), 0.87 (0.79–0.93; p < 0.001), and 0.76 (0.67–0.84; p = 0.006) respectively. Conclusions: The novelty of our study was the ability to predict 30-day mortality by serum TAC concentrations at any time during the first week of TBI. Full article
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Open AccessArticle
Chronic Chemogenetic Stimulation of the Nucleus Accumbens Produces Lasting Reductions in Binge Drinking and Ameliorates Alcohol-Related Morphological and Transcriptional Changes
Brain Sci. 2020, 10(2), 109; https://doi.org/10.3390/brainsci10020109 - 18 Feb 2020
Viewed by 218
Abstract
Binge drinking is a dangerous pattern of behavior. We tested whether chronically manipulating nucleus accumbens (NAc) activity (via clozapine-N-oxide (CNO) and Designer Receptors Exclusively Activated by Designer Drugs (DREADD)) could produce lasting effects on ethanol binge-like drinking in mice selectively bred to drink [...] Read more.
Binge drinking is a dangerous pattern of behavior. We tested whether chronically manipulating nucleus accumbens (NAc) activity (via clozapine-N-oxide (CNO) and Designer Receptors Exclusively Activated by Designer Drugs (DREADD)) could produce lasting effects on ethanol binge-like drinking in mice selectively bred to drink to intoxication. We found chronically increasing NAc activity (4 weeks, via CNO and the excitatory DREADD, hM3Dq) decreased binge-like drinking, but did not observe CNO-induced changes in drinking with the inhibitory DREADD, hM4Di. The CNO/hM3Dq-induced reduction in ethanol drinking persisted for at least one week, suggesting adaptive neuroplasticity via transcriptional and epigenetic mechanisms. Therefore, we defined this plasticity at the morphological and transcriptomic levels. We found that chronic binge drinking (6 weeks) altered neuronal morphology in the NAc, an effect that was ameliorated with CNO/hM3Dq. Moreover, we detected significant changes in expression of several plasticity-related genes with binge drinking that were ameliorated with CNO treatment (e.g., Hdac4). Lastly, we found that LMK235, an HDAC4/5 inhibitor, reduced binge-like drinking. Thus, we were able to target specific molecular pathways using pharmacology to mimic the behavioral effects of DREADDs. Full article
Open AccessArticle
Early Screening of the Autism Spectrum Disorders: Validity Properties and Cross-Cultural Generalizability of the First Year Inventory in Italy
Brain Sci. 2020, 10(2), 108; https://doi.org/10.3390/brainsci10020108 - 18 Feb 2020
Viewed by 213
Abstract
This study examined the cross-cultural generalisability of the First Year Inventory (FYI) on an Italian sample, testing its construct validity, consistency, and structural validity. Six hundred ninety-eight parents of children aged 11–13 months completed the questionnaire. Similarities between analyses of Italian and American/Israeli [...] Read more.
This study examined the cross-cultural generalisability of the First Year Inventory (FYI) on an Italian sample, testing its construct validity, consistency, and structural validity. Six hundred ninety-eight parents of children aged 11–13 months completed the questionnaire. Similarities between analyses of Italian and American/Israeli samples were found, as were demonstrations of the instrument’s construct validity and internal consistency with both groups. The original factorial structure was not demonstrated; thus, a new factorial structure was tested, and a short version of the FYI was demonstrated via confirmatory factor analysis. The findings supported the generalisability of the Italian version of the FYI and its validity. The FYI may aid in medical decision-making on further steps for referral of the child to an early diagnostic assessment. Full article
(This article belongs to the Special Issue Advances in Autism Research)
Open AccessOpinion
CDKL5 Deficiency Disorder—A Complex Epileptic Encephalopathy
Brain Sci. 2020, 10(2), 107; https://doi.org/10.3390/brainsci10020107 - 17 Feb 2020
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Abstract
CDKL5 deficiency disorder (CDD) is a complex of clinical symptoms resulting from the presence of non-functional CDKL5 protein, i.e., serine-threonine kinase (previously referred to as STK9), or its complete absence. The clinical picture is characterized by epileptic seizures (that start within the first [...] Read more.
CDKL5 deficiency disorder (CDD) is a complex of clinical symptoms resulting from the presence of non-functional CDKL5 protein, i.e., serine-threonine kinase (previously referred to as STK9), or its complete absence. The clinical picture is characterized by epileptic seizures (that start within the first three months of life and most often do not respond to pharmacological treatment), epileptic encephalopathy secondary to seizures, and retardation of psychomotor development, which are often observed already in the first months of life. Due to the fact that CDKL5 is located on the X chromosome, the prevalence of CDD among women is four times higher than in men. However, the course is usually more severe among male patients. Recently, many clinical centers have analyzed this condition and provided knowledge on the function of CDKL5 protein, the natural history of the disease, therapeutic options, and their effectiveness and prognosis. The International CDKL5 Disorder Database was established in 2012, which focuses its activity on expanding knowledge related to this condition and disseminating such knowledge to the families of patients. Full article
Open AccessArticle
The Impact of Removal of Ovarian Hormones on Cholinergic Muscarinic Receptors: Examining Prepulse Inhibition and Receptor Binding
Brain Sci. 2020, 10(2), 106; https://doi.org/10.3390/brainsci10020106 - 17 Feb 2020
Viewed by 193
Abstract
Ovarian hormones, such as estrogens and progesterone, are known to exert beneficial effects on cognition and some psychiatric disorders. The basis of these effects is not fully understood, but may involve altered cholinergic neurotransmission. This study aimed to investigate how a lack of [...] Read more.
Ovarian hormones, such as estrogens and progesterone, are known to exert beneficial effects on cognition and some psychiatric disorders. The basis of these effects is not fully understood, but may involve altered cholinergic neurotransmission. This study aimed to investigate how a lack of ovarian hormones would impact muscarinic receptor-induced deficits in prepulse inhibition (PPI) and muscarinic receptor density in several brain regions. Adult female rats were either ovariectomized, to remove the source of ovarian hormones, or left intact (sham-operated). PPI is a measure of sensorimotor gating that is typically impaired in schizophrenia patients, and similar deficits can be induced in rats by administering scopolamine, a muscarinic receptor antagonist. Our results revealed no significant effects of ovariectomy on PPI after saline or scopolamine treatment. Autoradiography was performed to measure cholinergic muscarinic receptor binding density using [3H]-pirenzepine, [3H]-AF-DX, and [3H]-4-DAMP, to label M1, M2/M4, and M3 receptors, respectively. We examined the amygdala, caudate putamen, dorsal hippocampus, motor cortex, retrosplenial cortex, and ventromedial hypothalamus. There were no significant group differences in any region for any muscarinic receptor type. These results suggest that removing peripheral ovarian hormones does not influence the cholinergic muscarinic receptor system in the context of PPI or receptor binding density. Full article
(This article belongs to the Special Issue Hormones and Cognition)
Open AccessArticle
Focus on Clozapine Withdrawal- and Misuse-Related Cases as Reported to the European Medicines Agency (EMA) Pharmacovigilance Database
Brain Sci. 2020, 10(2), 105; https://doi.org/10.3390/brainsci10020105 - 16 Feb 2020
Viewed by 356
Abstract
Background: Clozapine is of high clinical relevance for the management of both treatment-resistant schizophrenia and psychotic disturbances with concurrent drug misuse. Although the molecule presents with a range of well-known side-effects, its discontinuation/withdrawal syndrome has been only anecdotally described. Aims: the 2005–2018 European [...] Read more.
Background: Clozapine is of high clinical relevance for the management of both treatment-resistant schizophrenia and psychotic disturbances with concurrent drug misuse. Although the molecule presents with a range of well-known side-effects, its discontinuation/withdrawal syndrome has been only anecdotally described. Aims: the 2005–2018 European Medicines Agency (EMA) dataset of Adverse Drug Reactions (ADRs) was analyzed to identify and describe possible clozapine withdrawal- and misuse-/abuse-/dependence-related issues. Method: A descriptive analysis of clozapine-related ADRs was performed when available, data on ADRs’ outcome, dosage, and possible concomitant drug(s) were considered. Results: Out of 11,847 clozapine-related ADRs, some 599 (5.05%) were related to misuse/abuse/dependence/withdrawal issues, including 258 withdrawal-related (43.1%); 241 abuse-related (40.2%); and 80 intentional product misuse-related (13.3%) ADRs. A small number of overdose- and suicide-related ADRs were reported as well. Clozapine was typically (69.2%) identified alone, and most (84.7%) fatalities/high-dosage intake instances were reported in association with a history of substance abuse. Conclusions: Previous suggestions about the possibility of a clozapine discontinuation/withdrawal occurrence are here supported, but further studies are needed. However, the misuse/abuse cases here identified might be difficult to interpret, given the lack of studies highlighting the possible recreational use of clozapine. The high-dosage intake, fatal outcomes and clozapine/polydrug abuse issues reported here may, however, be a reason for concern. Full article
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Open AccessArticle
Emotional Response Inhibition: A Shared Neurocognitive Deficit in Eating Disorder Symptoms and Nonsuicidal Self-Injury
Brain Sci. 2020, 10(2), 104; https://doi.org/10.3390/brainsci10020104 - 15 Feb 2020
Viewed by 212
Abstract
Eating disorder (ED) symptoms often co-occur with non-suicidal self-injury (NSSI). This comorbidity is consistent with evidence that trait negative urgency increases risk for both of these phenomena. We previously found that impaired late-stage negative emotional response inhibition (i.e., negative emotional action termination or [...] Read more.
Eating disorder (ED) symptoms often co-occur with non-suicidal self-injury (NSSI). This comorbidity is consistent with evidence that trait negative urgency increases risk for both of these phenomena. We previously found that impaired late-stage negative emotional response inhibition (i.e., negative emotional action termination or NEAT) might represent a neurocognitive mechanism for heightened negative urgency among people with NSSI history. The current study evaluated whether relations between negative urgency and ED symptoms similarly reflect deficits in this neurocognitive process. A total of 105 community adults completed an assessment of ED symptoms, negative urgency, and an emotional response inhibition task. Results indicated that, contrary to predictions, negative urgency and NEAT contributed independent variance to the prediction of ED symptoms, while controlling for demographic covariates and NSSI history. Worse NEAT was also uniquely associated with restrictive eating, after accounting for negative urgency. Our findings suggest that difficulty inhibiting ongoing motor responses triggered by negative emotional reactions (i.e., NEAT) may be a shared neurocognitive characteristic of ED symptoms and NSSI. However, negative urgency and NEAT dysfunction capture separate variance in the prediction of ED-related cognitions and behaviors, distinct from the pattern of results we previously observed in NSSI. Full article
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Open AccessEditorial
Sex Stratified Treatment of Neurological Disorders: Challenges and Perspectives
Brain Sci. 2020, 10(2), 103; https://doi.org/10.3390/brainsci10020103 - 14 Feb 2020
Viewed by 305
Abstract
Despite the obvious sex differences in many of the most common neuropsychiatric and neurodegenerative disorders, males and females are still often treated the same from a clinical perspective. Why is that? The simple answer is that there is still too little known about [...] Read more.
Despite the obvious sex differences in many of the most common neuropsychiatric and neurodegenerative disorders, males and females are still often treated the same from a clinical perspective. Why is that? The simple answer is that there is still too little known about this very complex matter. Sex hormone signaling, genetic sex, sex-biased comorbidities, and social gender perceptions all interact, making discrimination between the impacts of each of these factors hard to evaluate. Adding to the complexity is that important species differences must be taken into account when interpreting data from animal models. Clearly, to overcome this, larger efforts are needed that incorporate epidemiological, experimental, and clinical data to provide a solid scientific base for more personalized and informed clinical decisions that will benefit both men and women suffering from neurological disorders. Full article
Open AccessReview
Exclusion Criteria Used in Early Behavioral Intervention Studies for Young Children with Autism Spectrum Disorder
Brain Sci. 2020, 10(2), 99; https://doi.org/10.3390/brainsci10020099 - 13 Feb 2020
Viewed by 261
Abstract
This literature review evaluated early behavioral intervention studies of Autism Spectrum disorder (ASD) based on their participant exclusion criteria. The studies included were found through searching PsycINFO and PubMed databases, and discussed behavioral interventions for children up to 5 years of age with [...] Read more.
This literature review evaluated early behavioral intervention studies of Autism Spectrum disorder (ASD) based on their participant exclusion criteria. The studies included were found through searching PsycINFO and PubMed databases, and discussed behavioral interventions for children up to 5 years of age with ASD and utilized a group research design. Studies reviewed were categorized into three groups: Restrictive exclusion criteria, loosely defined exclusion criteria, and exclusion criteria not defined. Results indicated that studies that used restrictive exclusion criteria demonstrated greater differences in terms of outcomes between experimental and control groups in comparison to studies that used loosely defined exclusion criteria and/or did not define any exclusion criteria. We discussed implications for the generalizability of the studies’ outcomes in relationship to exclusion criteria. Full article
(This article belongs to the Special Issue Advances in Autism Research)
Open AccessReview
A Systematic Review of Human Neuroimaging Evidence of Memory-Related Functional Alterations Associated with Cannabis Use Complemented with Preclinical and Human Evidence of Memory Performance Alterations
Brain Sci. 2020, 10(2), 102; https://doi.org/10.3390/brainsci10020102 - 13 Feb 2020
Viewed by 228
Abstract
Cannabis has been associated with deficits in memory performance. However, the neural correlates that may underpin impairments remain unclear. We carried out a systematic review of functional magnetic resonance imaging (fMRI) studies investigating brain functional alterations in cannabis users (CU) compared to nonusing [...] Read more.
Cannabis has been associated with deficits in memory performance. However, the neural correlates that may underpin impairments remain unclear. We carried out a systematic review of functional magnetic resonance imaging (fMRI) studies investigating brain functional alterations in cannabis users (CU) compared to nonusing controls while performing memory tasks, complemented with focused narrative reviews of relevant preclinical and human studies. Twelve studies employing fMRI were identified finding functional brain activation during memory tasks altered in CU. Memory performance studies showed CU performed worse particularly during verbal memory tasks. Longitudinal studies suggest that cannabis use may have a causal role in memory deficits. Preclinical studies have not provided conclusive evidence of memory deficits following cannabinoid exposure, although they have shown evidence of cannabinoid-induced structural and histological alteration. Memory performance deficits may be related to cannabis use, with lower performance possibly underpinned by altered functional activation. Memory impairments may be associated with the level of cannabis exposure and use of cannabis during developmentally sensitive periods, with possible improvement following cessation of cannabis use. Full article
(This article belongs to the Special Issue Cannabis: Neuropsychiatry and Its Effects on Brain and Behavior)
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Open AccessFeature PaperReview
Saccular Aneurysm Models Featuring Growth and Rupture: A Systematic Review
Brain Sci. 2020, 10(2), 101; https://doi.org/10.3390/brainsci10020101 - 13 Feb 2020
Viewed by 223
Abstract
Background. Most available large animal extracranial aneurysm models feature healthy non-degenerated aneurysm pouches with stable long-term follow-ups and extensive healing reactions after endovascular treatment. This review focuses on a small subgroup of extracranial aneurysm models that demonstrated growth and potential rupture during follow-up. [...] Read more.
Background. Most available large animal extracranial aneurysm models feature healthy non-degenerated aneurysm pouches with stable long-term follow-ups and extensive healing reactions after endovascular treatment. This review focuses on a small subgroup of extracranial aneurysm models that demonstrated growth and potential rupture during follow-up. Methods. The literature was searched in Medline/Pubmed to identify extracranial in vivo saccular aneurysm models featuring growth and rupture, using a predefined search strategy in accordance with the PRISMA guidelines. From eligible studies we extracted the following details: technique and location of aneurysm creation, aneurysm pouch characteristics, time for model creation, growth and rupture rate, time course, patency rate, histological findings, and associated morbidity and mortality. Results. A total of 20 articles were found to describe growth and/or rupture of an experimentally created extracranial saccular aneurysm during follow-up. Most frequent growth was reported in rats (n = 6), followed by rabbits (n = 4), dogs (n = 4), swine (n = 5), and sheep (n = 1). Except for two studies reporting growth and rupture within the abdominal cavity (abdominal aortic artery; n = 2) all other aneurysms were located at the neck of the animal. The largest growth rate, with an up to 10-fold size increase, was found in a rat abdominal aortic sidewall aneurysm model. Conclusions. Extracranial saccular aneurysm models with growth and rupture are rare. Degradation of the created aneurysmal outpouch seems to be a prerequisite to allow growth, which may ultimately lead to rupture. Since it has been shown that the aneurysm wall is important for healing after endovascular therapy, it is likely that models featuring growth and rupture will gain in interest for preclinical testing of novel endovascular therapies. Full article
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Open AccessArticle
Manual Dexterity is not Related to Media Viewing but is Related to Perceptual Bias in School-Age Children
Brain Sci. 2020, 10(2), 100; https://doi.org/10.3390/brainsci10020100 - 13 Feb 2020
Viewed by 384
Abstract
Although the media can have both negative and positive effects on children’s cognitive and motor functions, its influence on their perceptual bias and manual dexterity is unclear. Thus, we investigated the association between media viewing time, media preference level, perceptual bias, and manual [...] Read more.
Although the media can have both negative and positive effects on children’s cognitive and motor functions, its influence on their perceptual bias and manual dexterity is unclear. Thus, we investigated the association between media viewing time, media preference level, perceptual bias, and manual dexterity in 100 school-aged children. Questionnaires completed by children and their parents were used to ascertain media viewing time and preference levels. Perceptual bias and manual dexterity were measured using the visual-tactile temporal order judgment task and Movement Assessment Battery for Children—2nd edition, respectively. There were significant positive correlations between age and media viewing time and between media viewing time and media preference level. There was also a significant negative correlation between visual bias and manual dexterity. Hierarchical multiple regression analysis revealed that increasing visual bias was a significant predictor of decreasing manual dexterity. Further, children with low manual dexterity showed significant visual bias compared to those with high manual dexterity, when matched for age and gender. The present results demonstrated that, in school-aged children, although viewing media was not associated with perceptual bias and manual dexterity, there was a significant association between perceptual bias and manual dexterity. Full article
Open AccessArticle
Understanding Exercise Adherence: The Predictability of Past Experience and Motivational Determinants
Brain Sci. 2020, 10(2), 98; https://doi.org/10.3390/brainsci10020098 - 12 Feb 2020
Viewed by 314
Abstract
Background: An unresolved debate lingers over the effect of past behavior on motivational patterns and future behavior stability in the exercise context. Theorists argue that past behavior has a residual effect on future behavior; however, empirical studies have shown that past behavior displays [...] Read more.
Background: An unresolved debate lingers over the effect of past behavior on motivational patterns and future behavior stability in the exercise context. Theorists argue that past behavior has a residual effect on future behavior; however, empirical studies have shown that past behavior displays significant power in predicting behavior recurrence in the future. The present research aimed to examine the effect of past behavior and motivational determinants on future exercise adherence. Methods: Data from 437 Portuguese gym exercisers (female = 235; male = 202) aged between 18 and 53 years (M = 31.14; SD = 9.47), with exercise experience ranging from 6 to 12 months (M = 9.41; SD = 1.33) were considered for research. Participants completed a multi-section survey measuring interpersonal behaviors, basic psychological needs, behavioral regulations, and intentions. Data from past behavior and future exercise adherence were collected using computerized records of their attendance at the gym. Results: Positive and significant correlations paths were evidenced among perceived supportive behaviors, needs satisfaction, autonomous motivation, intentions and future exercise adherence. Similar results were presented among perceived thwarting behaviors, needs frustration, and controlled motivation. Regression paths showed that perceived supportive behavior, basic needs satisfaction, and autonomous motivation displayed positive and significant effects on future behaviors; thus, past behavior displayed the highest coefficient on future exercise adherence. Fitness professionals should aim at creating supportive environments, thus, improving the likelihood of being perceived by exercisers as need-supportive individuals. By doing so, as a result, exercisers would experience increased levels of autonomous motivation and higher rates of future exercise attendance at the gym. Hence, exercisers will gradually form their positive past exercise experience, increasing the probability of engaging in an exercise in the future. Full article
(This article belongs to the Section Cognitive Neuroscience)
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