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Brain Sci., Volume 11, Issue 11 (November 2021) – 180 articles

Cover Story (view full-size image): Due to constant interactions with technology, neck fatigue is very common. Short latency somatosensory evoked potentials (SEPs) measure changes in the brain pathways. Both the N24 SEP (likely reflecting increased inhibition in the cerebellum to S1 pathway) and the N30 SEP (reflecting subcortical and cortical loops connecting basal ganglia, thalamus, pre-motor areas, and primary motor cortex) increased when fatigue preceded motor acquisition. Fatigue also led to worse performance after acquisition and retention of a novel motor tracking task. Altered neck inputs due to fatigue appear to alter the way that cerebellar and sensorimotor integration pathways respond to learning new skills. View this paper
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Article
Programmable Shunt Valves for Pediatric Hydrocephalus: 22-Year Experience from a Singapore Children’s Hospital
Brain Sci. 2021, 11(11), 1548; https://doi.org/10.3390/brainsci11111548 - 22 Nov 2021
Viewed by 383
Abstract
(1) Background: pediatric hydrocephalus is a challenging condition. Programmable shunt valves (PSV) have been increasingly used. This study is undertaken to firstly, to objectively evaluate the efficacy of PSV as a treatment modality for pediatric hydrocephalus; and next, review its associated patient outcomes [...] Read more.
(1) Background: pediatric hydrocephalus is a challenging condition. Programmable shunt valves (PSV) have been increasingly used. This study is undertaken to firstly, to objectively evaluate the efficacy of PSV as a treatment modality for pediatric hydrocephalus; and next, review its associated patient outcomes at our institution. Secondary objectives include the assessment of our indications for PSV, and corroboration of our results with published literature. (2) Methods: this is an ethics-approved, retrospective study. Variables of interest include age, gender, hydrocephalus etiology, shunt failure rates and incidence of adjustments made per PSV. Data including shunt failure, implant survival, and utility comparisons between PSV types are subjected to statistical analyses. (3) Results: in this case, 51 patients with PSV are identified for this study, with 32 index and 19 revision shunts. There are 3 cases of shunt failure (6%). The mean number of adjustments per PSV is 1.82 times and the mean number of adjustments made per PSV is significantly lower for MEDTRONIC™ Strata PSVs compared with others (p = 0.031). Next, PSV patients that are adjusted more frequently include cases of shunt revisions, PSVs inserted due to CSF over-drainage and tumor-related hydrocephalus. (4) Conclusion: we describe our institutional experience of PSV use in pediatric hydrocephalus and its advantages in a subset of patients whose opening pressures are uncertain and evolving. Full article
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Review
Is Aducanumab for LMICs? Promises and Challenges
Brain Sci. 2021, 11(11), 1547; https://doi.org/10.3390/brainsci11111547 - 22 Nov 2021
Viewed by 332
Abstract
Aducanumab, a human monoclonal antibody, was approved in June of 2021 as the first disease-modifying treatment for Alzheimer’s disease by the United States Food and Drug Administration (U.S. FDA). A substantial proportion of patients with Alzheimer’s disease live in low- and middle-income countries [...] Read more.
Aducanumab, a human monoclonal antibody, was approved in June of 2021 as the first disease-modifying treatment for Alzheimer’s disease by the United States Food and Drug Administration (U.S. FDA). A substantial proportion of patients with Alzheimer’s disease live in low- and middle-income countries (LMICs), and the debilitating effects of this disease exerts burdens on patients and caregivers in addition to the significant economic strains many nations bear. While the advantages of a disease-modifying therapy are clear in delaying the progression of disease to improve patient outcomes, aducanumab’s approval by the U.S. FDA was met with controversy for a plethora of reasons. This paper will provide precursory insights into aducanumab’s role, appropriateness, and cost-effectiveness in low- and middle-income countries. We extend some of the controversies associated with aducanumab, including the contradicting evidence from the two trials (EMERGE and ENGAGE) and the resources required to deliver the treatment safely and effectively to patients, among other key considerations. Full article
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Article
Impact of Early Rhythmic Training on Language Acquisition and Electrophysiological Functioning Underlying Auditory Processing: Feasibility and Preliminary Findings in Typically Developing Infants
Brain Sci. 2021, 11(11), 1546; https://doi.org/10.3390/brainsci11111546 - 21 Nov 2021
Viewed by 281
Abstract
Previous evidence has shown that early auditory processing impacts later linguistic development, and targeted training implemented at early ages can enhance auditory processing skills, with better expected language development outcomes. This study focuses on typically developing infants and aims to test the feasibility [...] Read more.
Previous evidence has shown that early auditory processing impacts later linguistic development, and targeted training implemented at early ages can enhance auditory processing skills, with better expected language development outcomes. This study focuses on typically developing infants and aims to test the feasibility and preliminary efficacy of music training based on active synchronization with complex musical rhythms on the linguistic outcomes and electrophysiological functioning underlying auditory processing. Fifteen infants participated in the training (RTr+) and were compared with two groups of infants not attending any structured activities during the same time frame (RTr−, N = 14). At pre- and post-training, expressive and receptive language skills were assessed using standardized tests, and auditory processing skills were characterized through an electrophysiological non-speech multi-feature paradigm. Results reveal that RTr+ infants showed significantly broader improvement in both expressive and receptive pre-language skills. Moreover, at post-training, they presented an electrophysiological pattern characterized by shorter latency of two peaks (N2* and P2), reflecting a neural change detection process: these shifts in latency go beyond those seen due to maturation alone. These results provide preliminary evidence on the efficacy of our training in improving early linguistic competences, and in modifying the neural underpinnings of auditory processing in infants. Full article
(This article belongs to the Special Issue Advances in Music-Related Neuroplasticity: Mechanisms and Medicine)
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Systematic Review
Endogenous Oxytocin Levels in Autism—A Meta-Analysis
Brain Sci. 2021, 11(11), 1545; https://doi.org/10.3390/brainsci11111545 - 21 Nov 2021
Viewed by 242
Abstract
Oxytocin (OT) circuitry plays a major role in the mediation of prosocial behavior. Individuals with autism spectrum disorder (ASD) are characterized by impairments in social interaction and communication and have been suggested to display deficiencies in central OT mechanisms. The current preregistered meta-analysis [...] Read more.
Oxytocin (OT) circuitry plays a major role in the mediation of prosocial behavior. Individuals with autism spectrum disorder (ASD) are characterized by impairments in social interaction and communication and have been suggested to display deficiencies in central OT mechanisms. The current preregistered meta-analysis evaluated potential group differences in endogenous OT levels between individuals with ASD and neurotypical (NT) controls. We included 18 studies comprising a total of 1422 participants. We found that endogenous OT levels are lower in children with ASD as compared to NT controls (n = 1123; g = −0.60; p = 0.006), but this effect seems to disappear in adolescent (n = 152; g = −0.20; p = 0.53) and adult populations (n = 147; g = 0.27; p = 0.45). Secondly, while no significant subgroup differences were found in regard to sex, the group difference in OT levels of individuals with versus without ASD seems to be only present in the studies with male participants (n = 814; g = −0.44; p = 0.08) and not female participants (n = 192; g = 0.11; p = 0.47). More research that employs more homogeneous methods is necessary to investigate potential developmental changes in endogenous OT levels, both in typical and atypical development, and to explore the possible use of OT level measurement as a diagnostic marker of ASD. Full article
(This article belongs to the Special Issue Hypothalamus, Neuropeptides and Socioemotional Behavior)
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Systematic Review
Prevalence of Individuals at Clinical High-Risk of Psychosis in the General Population and Clinical Samples: Systematic Review and Meta-Analysis
Brain Sci. 2021, 11(11), 1544; https://doi.org/10.3390/brainsci11111544 - 20 Nov 2021
Viewed by 439
Abstract
(1) The consistency and magnitude of the prevalence of Clinical High-Risk for Psychosis (CHR-P) individuals are undetermined, limiting efficient detection of cases. We aimed to evaluate the prevalence of CHR-P individuals systematically assessed in the general population or clinical samples. (2) PRISMA/MOOSE-compliant (PROSPERO: [...] Read more.
(1) The consistency and magnitude of the prevalence of Clinical High-Risk for Psychosis (CHR-P) individuals are undetermined, limiting efficient detection of cases. We aimed to evaluate the prevalence of CHR-P individuals systematically assessed in the general population or clinical samples. (2) PRISMA/MOOSE-compliant (PROSPERO: CRD42020168672) meta-analysis of multiple databases until 21/01/21: a random-effects model meta-analysis, heterogeneity analysis, publication bias and quality assessment, sensitivity analysis—according to the gold-standard CHR-P and pre-screening instruments—leave-one-study-out analyses, and meta-regressions were conducted. (3) 35 studies were included, with 37,135 individuals tested and 1554 CHR-P individuals identified (median age = 19.3 years, Interquartile range (IQR) = 15.8–22.1; 52.2% females, IQR = 38.7–64.4). In the general population (k = 13, n = 26,835 individuals evaluated), the prevalence of the CHR-P state was 1.7% (95% Confidence Interval (CI) = 1.0–2.9%). In clinical samples (k = 22, n = 10,300 individuals evaluated), the prevalence of the CHR-P state was 19.2% (95% CI = 12.9–27.7%). Using a pre-screening instrument was associated with false negatives (5.6%, 95% CI = 2.2–13.3%) and a lower CHR-P prevalence (11.5%, 95% CI = 6.2–20.5%) compared to using CHR-P instruments only (28.5%, 95% CI = 23.0–34.7%, p = 0.003). (4) The prevalence of the CHR-P state is low in the general population and ten times higher in clinical samples. The prevalence of CHR-P may increase with a higher proportion of females in the general population and with a younger population in clinical samples. The CHR-P state may be unrecognized in routine clinical practice. These findings can refine detection and preventive strategies. Full article
(This article belongs to the Section Psychiatric Diseases)
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Article
Epigenetic Small Molecules Rescue Nucleocytoplasmic Transport and DNA Damage Phenotypes in C9ORF72 ALS/FTD
Brain Sci. 2021, 11(11), 1543; https://doi.org/10.3390/brainsci11111543 - 20 Nov 2021
Viewed by 400
Abstract
Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease with available treatments only marginally slowing progression or improving survival. A hexanucleotide repeat expansion mutation in the C9ORF72 gene is the most commonly known genetic cause of both sporadic and familial cases [...] Read more.
Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease with available treatments only marginally slowing progression or improving survival. A hexanucleotide repeat expansion mutation in the C9ORF72 gene is the most commonly known genetic cause of both sporadic and familial cases of ALS and frontotemporal dementia (FTD). The C9ORF72 expansion mutation produces five dipeptide repeat proteins (DPRs), and while the mechanistic determinants of DPR-mediated neurotoxicity remain incompletely understood, evidence suggests that disruption of nucleocytoplasmic transport and increased DNA damage contributes to pathology. Therefore, characterizing these disturbances and determining the relative contribution of different DPRs is needed to facilitate the development of novel therapeutics for C9ALS/FTD. To this end, we generated a series of nucleocytoplasmic transport “biosensors”, composed of the green fluorescent protein (GFP), fused to different classes of nuclear localization signals (NLSs) and nuclear export signals (NESs). Using these biosensors in conjunction with automated microscopy, we investigated the role of the three most neurotoxic DPRs (PR, GR, and GA) on seven nuclear import and two export pathways. In addition to other DPRs, we found that PR had pronounced inhibitory effects on the classical nuclear export pathway and several nuclear import pathways. To identify compounds capable of counteracting the effects of PR on nucleocytoplasmic transport, we developed a nucleocytoplasmic transport assay and screened several commercially available compound libraries, totaling 2714 compounds. In addition to restoring nucleocytoplasmic transport efficiencies, hits from the screen also counteract the cytotoxic effects of PR. Selected hits were subsequently tested for their ability to rescue another C9ALS/FTD phenotype—persistent DNA double strand breakage. Overall, we found that DPRs disrupt multiple nucleocytoplasmic transport pathways and we identified small molecules that counteract these effects—resulting in increased viability of PR-expressing cells and decreased DNA damage markers in patient-derived motor neurons. Several HDAC inhibitors were validated as hits, supporting previous studies that show that HDAC inhibitors confer therapeutic effects in neurodegenerative models. Full article
(This article belongs to the Section Neurodegenerative Diseases)
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Article
Flexible Use of Spatial Frames of Reference for Object–Location Memory in Older Adults
Brain Sci. 2021, 11(11), 1542; https://doi.org/10.3390/brainsci11111542 - 20 Nov 2021
Viewed by 350
Abstract
In memory, representations of spatial features are stored in different reference frames; features relative to our position are stored egocentrically and features relative to each other are stored allocentrically. Accessing these representations engages many cognitive and neural resources, and so is susceptible to [...] Read more.
In memory, representations of spatial features are stored in different reference frames; features relative to our position are stored egocentrically and features relative to each other are stored allocentrically. Accessing these representations engages many cognitive and neural resources, and so is susceptible to age-related breakdown. Yet, recent findings on the heterogeneity of cognitive function and spatial ability in healthy older adults suggest that aging may not uniformly impact the flexible use of spatial representations. These factors have yet to be explored in a precisely controlled task that explicitly manipulates spatial frames of reference across learning and retrieval. We used a lab-based virtual reality task to investigate the relationship between object–location memory across frames of reference, cognitive status, and self-reported spatial ability. Memory error was measured using Euclidean distance from studied object locations to participants’ responses at testing. Older adults recalled object locations less accurately when they switched between frames of reference from learning to testing, compared with when they remained in the same frame of reference. They also showed an allocentric learning advantage, producing less error when switching from an allocentric to an egocentric frame of reference, compared with the reverse direction of switching. Higher MoCA scores and better self-assessed spatial ability predicted less memory error, especially when learning occurred egocentrically. We suggest that egocentric learning deficits are driven by difficulty in binding multiple viewpoints into a coherent representation. Finally, we highlight the heterogeneity of spatial memory performance in healthy older adults as a potential cognitive marker for neurodegeneration, beyond normal aging. Full article
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Article
Anxiety, Perceived Stress, and Resilience during the COVID-19 Pandemic: Population Estimates of Persons Presenting to a General Practitioner in Romania
Brain Sci. 2021, 11(11), 1541; https://doi.org/10.3390/brainsci11111541 - 20 Nov 2021
Viewed by 374
Abstract
Facing the COVID-19 pandemic, individuals are experiencing severe mental distress. Thus, during the last year, drastic changes occurred in everyday life of every human being. Following social distancing and economic insecurity, significant increases in mental health concerns (loneliness, anxiety, depression, or insomnia) have [...] Read more.
Facing the COVID-19 pandemic, individuals are experiencing severe mental distress. Thus, during the last year, drastic changes occurred in everyday life of every human being. Following social distancing and economic insecurity, significant increases in mental health concerns (loneliness, anxiety, depression, or insomnia) have developed. The objective of this study was to explore the anxiety, perceived stress, and resilience in a population presenting at the general practitioner, during the COVID-19 pandemic. Data were collected between February and April 2021 and 440 individuals who presented to the general practitioner were evaluated. Concerning anxiety level, almost half of the respondents (49,3%, N = 217) scored above the threshold value on the anxiety scale (mild intensity 38.6%, moderate intensity 9.9%, severe intensity 0.8%). Having a low level of resilience, as well as experiencing a high level of stress, are both predictive of the occurrence of high anxiety (p < 0.001, r = −0.551 and p < 0.001, r = 0.622, respectively). Furthermore, resilience is negatively related to perceived stress (p < 0.001, r = −0.676). It is critical in the current crisis to recognize those at risk of developing mental illnesses, taking into consideration the various socioeconomic classes, as well as to maintain and improve the general public’s mental health using appropriate psychological interventions. Full article
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Article
Utility of the Intelligibility in Context Scale for Predicting Speech Intelligibility of Children with Cerebral Palsy
Brain Sci. 2021, 11(11), 1540; https://doi.org/10.3390/brainsci11111540 - 20 Nov 2021
Viewed by 431
Abstract
The Intelligibility in Context Scale (ICS) is a widely used, efficient tool for describing a child’s speech intelligibility. Few studies have explored the relationship between ICS scores and transcription intelligibility scores, which are the gold standard for clinical measurement. This study examined how [...] Read more.
The Intelligibility in Context Scale (ICS) is a widely used, efficient tool for describing a child’s speech intelligibility. Few studies have explored the relationship between ICS scores and transcription intelligibility scores, which are the gold standard for clinical measurement. This study examined how well ICS composite scores predicted transcription intelligibility scores among children with cerebral palsy (CP), how well individual questions from the ICS differentially predicted transcription intelligibility scores, and how well the ICS composite scores differentiated between children with and without speech motor impairment. Parents of 48 children with CP, who were approximately 13 years of age, completed the ICS. Ninety-six adult naïve listeners provided orthographic transcriptions of children’s speech. Transcription intelligibility scores were regressed on ICS composite scores and individual item scores. Dysarthria status was regressed on ICS composite scores. Results indicated that ICS composite scores were moderately strong predictors of transcription intelligibility scores. One individual ICS item differentially predicted transcription intelligibility scores, and dysarthria severity influenced how well ICS composite scores differentiated between children with and without speech motor impairment. Findings suggest that the ICS has potential clinical utility for children with CP, especially when used with other objective measures of speech intelligibility. Full article
(This article belongs to the Special Issue Profiles of Dysarthria: Clinical Assessment and Treatment)
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Article
An Exploratory Study on Resting-State Functional Connectivity in Individuals with Disorganized Attachment: Evidence for Key Regions in Amygdala and Hippocampus
Brain Sci. 2021, 11(11), 1539; https://doi.org/10.3390/brainsci11111539 - 19 Nov 2021
Viewed by 275
Abstract
Studies comparing organized (O) and unresolved/disorganized (UD) attachment have consistently shown structural and functional brain abnormalities, although whether and how attachment patterns may affect resting state functional connectivity (RSFC) is still little characterized. Here, we investigated RSFC of temporal and limbic regions of [...] Read more.
Studies comparing organized (O) and unresolved/disorganized (UD) attachment have consistently shown structural and functional brain abnormalities, although whether and how attachment patterns may affect resting state functional connectivity (RSFC) is still little characterized. Here, we investigated RSFC of temporal and limbic regions of interest for UD attachment. Participants’ attachment was classified via the Adult Attachment Interview, and all participants underwent clinical assessment. Functional magnetic resonance imaging data were collected from 11 UD individuals and seven matched O participants during rest. A seed-to-voxel analysis was performed, including the anterior and the posterior cingulate cortex, the bilateral insula, amygdala and hippocampus as seed regions. No group differences in the clinical scales emerged. Compared to O, the UD group showed lower RSFC between the left amygdala and the left cerebellum (lobules VIII), and lower functional coupling between the right hippocampus and the posterior portion of the right middle temporal gyrus. Moreover, UD participants showed higher RSFC between the right amygdala and the anterior cingulate cortex. Our findings suggest RSFC alterations in regions associated with encoding of salient events, emotion processing, memories retrieval and self-referential processing in UD participants, highlighting the potential role of attachment experiences in shaping brain abnormalities also in non-clinical UD individuals. Full article
(This article belongs to the Section Neuropsychology)
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Article
MR Spectroscopy of the Insula: Within- and between-Session Reproducibility of MEGA-PRESS Measurements of GABA+ and Other Metabolites
Brain Sci. 2021, 11(11), 1538; https://doi.org/10.3390/brainsci11111538 - 19 Nov 2021
Viewed by 279
Abstract
The insula plays a critical role in many neuropsychological disorders. Research investigating its neurochemistry with magnetic resonance spectroscopy (MRS) has been limited compared with cortical regions. Here, we investigate the within-session and between-session reproducibility of metabolite measurements in the insula on a 3T [...] Read more.
The insula plays a critical role in many neuropsychological disorders. Research investigating its neurochemistry with magnetic resonance spectroscopy (MRS) has been limited compared with cortical regions. Here, we investigate the within-session and between-session reproducibility of metabolite measurements in the insula on a 3T scanner. We measure N-acetylaspartate + N-acetylaspartylglutamate (tNAA), creatine + phosphocreatine (tCr), glycerophosphocholine + phosphocholine (tCho), myo-inositol (Ins), glutamate + glutamine (Glx), and γ-aminobutyric acid (GABA) in one cohort using a j-edited MEGA-PRESS sequence. We measure tNAA, tCr, tCho, Ins, and Glx in another cohort with a standard short-TE PRESS sequence as a reference for the reproducibility metrics. All participants were scanned 4 times identically: 2 back-to-back scans each day, on 2 days. Preprocessing was done using LCModel and Gannet. Reproducibility was determined using Pearson’s r, intraclass-correlation coefficients (ICC), coefficients of variation (CV%), and Bland–Altman plots. A MEGA-PRESS protocol requiring averaged results over two 6:45-min scans yielded reproducible GABA measurements (CV% = 7.15%). This averaging also yielded reproducibility metrics comparable to those from PRESS for the other metabolites. Voxel placement inconsistencies did not affect reproducibility, and no sex differences were found. The data suggest that MEGA-PRESS can reliably measure standard metabolites and GABA in the insula. Full article
(This article belongs to the Collection Insula: Rediscovering the Hidden Lobe of the Brain)
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Article
Effects of Force Modulation on Large Muscles during Human Cycling
Brain Sci. 2021, 11(11), 1537; https://doi.org/10.3390/brainsci11111537 - 19 Nov 2021
Viewed by 253
Abstract
Voluntary force modulation is defined as the ability to tune the application of force during motion. However, the mechanisms behind this modulation are not yet fully understood. In this study, we examine muscle activity under various resistance levels at a fixed cycling speed. [...] Read more.
Voluntary force modulation is defined as the ability to tune the application of force during motion. However, the mechanisms behind this modulation are not yet fully understood. In this study, we examine muscle activity under various resistance levels at a fixed cycling speed. The main goal of this research is to identify significant changes in muscle activation related to the real-time tuning of muscle force. This work revealed significant motor adaptations of the main muscles utilized in cycling as well as positive associations between the force level and the temporal and spatial inter-cycle stability in the distribution of sEMG activity. From these results, relevant biomarkers of motor adaptation could be extracted for application in clinical rehabilitation to increase the efficacy of physical therapy. Full article
(This article belongs to the Special Issue Applications of Neurotechnologies in People with Walking Disabilities)
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Article
From aMCI to AD: The Role of Visuo-Spatial Memory Span and Executive Functions in Egocentric and Allocentric Spatial Impairments
Brain Sci. 2021, 11(11), 1536; https://doi.org/10.3390/brainsci11111536 - 19 Nov 2021
Viewed by 239
Abstract
A difficulty in encoding spatial information in an egocentric (i.e., body-to-object) and especially allocentric (i.e., object-to-object) manner, and impairments in executive function (EF) are typical in amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD). Since executive functions are involved in spatial encodings, [...] Read more.
A difficulty in encoding spatial information in an egocentric (i.e., body-to-object) and especially allocentric (i.e., object-to-object) manner, and impairments in executive function (EF) are typical in amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD). Since executive functions are involved in spatial encodings, it is important to understand the extent of their reciprocal or selective impairment. To this end, AD patients, aMCI and healthy elderly people had to provide egocentric (What object was closest to you?) and allocentric (What object was closest to object X?) judgments about memorized objects. Participants’ frontal functions, attentional resources and visual-spatial memory were assessed with the Frontal Assessment Battery (FAB), the Trail Making Test (TMT) and the Corsi Block Tapping Test (forward/backward). Results showed that ADs performed worse than all others in all tasks but did not differ from aMCIs in allocentric judgments and Corsi forward. Regression analyses showed, although to different degrees in the three groups, a link between attentional resources, visuo-spatial memory and egocentric performance, and between frontal resources and allocentric performance. Therefore, visuo-spatial memory, especially when it involves allocentric frames and requires demanding active processing, should be carefully assessed to reveal early signs of conversion from aMCI to AD. Full article
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Article
Relationship between Amyloid-β Deposition and the Coupling between Structural and Functional Brain Networks in Patients with Mild Cognitive Impairment and Alzheimer’s Disease
Brain Sci. 2021, 11(11), 1535; https://doi.org/10.3390/brainsci11111535 - 19 Nov 2021
Viewed by 262
Abstract
Previous studies have demonstrated that the accumulation of amyloid-β (Aβ) pathologies has distinctive stage-specific effects on the structural and functional brain networks along the Alzheimer’s disease (AD) continuum. A more comprehensive account of both types of brain network may provide a better characterization [...] Read more.
Previous studies have demonstrated that the accumulation of amyloid-β (Aβ) pathologies has distinctive stage-specific effects on the structural and functional brain networks along the Alzheimer’s disease (AD) continuum. A more comprehensive account of both types of brain network may provide a better characterization of the stage-specific effects of Aβ pathologies. A potential candidate for this joint characterization is the coupling between the structural and functional brain networks (SC-FC coupling). We therefore investigated the effect of Aβ accumulation on global SC-FC coupling in patients with mild cognitive impairment (MCI), AD, and healthy controls. Patients with MCI were dichotomized according to their level of Aβ pathology seen in 18F-flutemetamol PET-CT scans—namely, Aβ-negative and Aβ-positive. Our results show that there was no difference in global SC-FC coupling between different cohorts. During the prodromal AD stage, there was a significant negative correlation between the level of Aβ pathology and the global SC-FC coupling of MCI patients with positive Aβ, but no significant correlation for MCI patients with negative Aβ. During the AD dementia stage, the correlation between Aβ pathology and global SC-FC coupling in patients with AD was positive. Our results suggest that Aβ pathology has distinctive stage-specific effects on global coupling between the structural and functional brain networks along the AD continuum. Full article
(This article belongs to the Topic Mechanisms and Treatments of Neurodegenerative Diseases)
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Article
Aberrant Amplitude of Low-Frequency Fluctuation and Degree Centrality within the Default Mode Network in Patients with Vascular Mild Cognitive Impairment
Brain Sci. 2021, 11(11), 1534; https://doi.org/10.3390/brainsci11111534 - 19 Nov 2021
Viewed by 244
Abstract
This study aimed to investigate whole-brain spontaneous activities changes in patients with vascular mild cognitive impairment (VaMCI), and to evaluate the relationships between these brain alterations and their neuropsychological assessments. Thirty-one patients with VaMCI and thirty-one healthy controls (HCs) underwent structural MRI and [...] Read more.
This study aimed to investigate whole-brain spontaneous activities changes in patients with vascular mild cognitive impairment (VaMCI), and to evaluate the relationships between these brain alterations and their neuropsychological assessments. Thirty-one patients with VaMCI and thirty-one healthy controls (HCs) underwent structural MRI and resting-state functional MRI (rs-fMRI) and neuropsychological assessments. The functional alterations were determined by the amplitude of low-frequency fluctuation (ALFF) and degree centrality (DC). The gray matter volume (GMV) changes were analyzed using voxel-based morphometry (VBM). Linear regression analysis was used to evaluate the relationships between the structural and functional changes of brain regions and neuropsychological assessments. The VaMCI group had significantly lower scores in the Montreal Cognitive Assessment (MoCA), and higher scores on the Hamilton Anxiety Rating Scale (HAMA) and Hamilton Depression Rating Scale (HAMD). Compared to the HCs, the VaMCI group exhibited GM atrophy in the right precentral gyrus (PreCG) and right inferior temporal gyrus (ITG). VaMCI patients further exhibited significantly decreased brain activity within the default mode network (DMN), including the bilateral precuneus (PCu), angular gyrus (AG), and medial frontal gyrus (medFG). Linear regression analysis revealed that the decreased ALFF was independently associated with lower MoCA scores, and the GM atrophy was independently associated with higher HAMD scores. The current finding suggested that aberrant spontaneous brain activity in the DMN might subserve as a potential biomarker of VaMCI, which may highlight the underlying mechanism of cognitive decline in cerebral small vessel disease. Full article
(This article belongs to the Special Issue Multimodal Data Fusion on Patients with Cognitive Impairment)
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Review
The Insula: A Stimulating Island of the Brain
Brain Sci. 2021, 11(11), 1533; https://doi.org/10.3390/brainsci11111533 - 19 Nov 2021
Viewed by 273
Abstract
Direct cortical stimulation (DCS) in epilepsy surgery patients has a long history of functional brain mapping and seizure triggering. Here, we review its findings when applied to the insula in order to map the insular functions, evaluate its local and distant connections, and [...] Read more.
Direct cortical stimulation (DCS) in epilepsy surgery patients has a long history of functional brain mapping and seizure triggering. Here, we review its findings when applied to the insula in order to map the insular functions, evaluate its local and distant connections, and trigger seizures. Clinical responses to insular DCS are frequent and diverse, showing a partial segregation with spatial overlap, including a posterior somatosensory, auditory, and vestibular part, a central olfactory-gustatory region, and an anterior visceral and cognitive-emotional portion. The study of cortico-cortical evoked potentials (CCEPs) has shown that the anterior (resp. posterior) insula has a higher connectivity rate with itself than with the posterior (resp. anterior) insula, and that both the anterior and posterior insula are closely connected, notably between the homologous insular subdivisions. All insular gyri show extensive and complex ipsilateral and contralateral extra-insular connections, more anteriorly for the anterior insula and more posteriorly for the posterior insula. As a rule, CCEPs propagate first and with a higher probability around the insular DCS site, then to the homologous region, and later to more distal regions with fast cortico-cortical axonal conduction delays. Seizures elicited by insular DCS have rarely been specifically studied, but their rate does not seem to differ from those of other DCS studies. They are mainly provoked from the insular seizure onset zone but can also be triggered by stimulating intra- and extra-insular early propagation zones. Overall, in line with the neuroimaging studies, insular DCS studies converge on the view that the insula is a multimodal functional hub with a fast propagation of information, whose organization helps understand where insular seizures start and how they propagate. Full article
(This article belongs to the Collection Insula: Rediscovering the Hidden Lobe of the Brain)
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Article
Modulation of Long-Term Potentiation by Gamma Frequency Transcranial Alternating Current Stimulation in Transgenic Mouse Models of Alzheimer’s Disease
Brain Sci. 2021, 11(11), 1532; https://doi.org/10.3390/brainsci11111532 - 19 Nov 2021
Viewed by 401
Abstract
Transcranial alternating current stimulation (tACS) is a neuromodulation procedure that is currently studied for the purpose of improving cognitive function in various diseases. A few studies have shown positive effects of tACS in Alzheimer’s disease (AD). However, the mechanism underlying tACS has not [...] Read more.
Transcranial alternating current stimulation (tACS) is a neuromodulation procedure that is currently studied for the purpose of improving cognitive function in various diseases. A few studies have shown positive effects of tACS in Alzheimer’s disease (AD). However, the mechanism underlying tACS has not been established. The purpose of this study was to investigate the mechanism of tACS in five familial AD mutation (5xFAD) mouse models. We prepared twenty 4-month-old mice and divided them into four groups: wild-type mice without stimulation (WT-NT group), wild-type mice with tACS (WT-T group), 5xFAD mice without stimulation (AD-NT group), and 5xFAD mice with tACS (AD-T group). The protocol implemented was as follows: gamma frequency 200 μA over the bilateral frontal lobe for 20 min over 2 weeks. The following tests were conducted: excitatory postsynaptic potential (EPSP) recording, Western blot analysis (cyclic AMP response element-binding (CREB) proteins, phosphorylated CREB proteins, brain-derived neurotrophic factor, and parvalbumin) to examine the synaptic plasticity. The EPSP was remarkably increased in the AD-T group compared with in the AD-NT group. In the Western blot analysis, the differences among the groups were not significant. Hence, tACS can affect the long-lasting enhancement of synaptic transmission in mice models of AD. Full article
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Article
Differences in Performance of ASD and ADHD Subjects Facing Cognitive Loads in an Innovative Reasoning Experiment
Brain Sci. 2021, 11(11), 1531; https://doi.org/10.3390/brainsci11111531 - 18 Nov 2021
Viewed by 542
Abstract
We aim to investigate whether EEG dynamics differ in adults with ASD (Autism Spectrum Disorders) and ADHD (attention-deficit/hyperactivity disorder) compared with healthy subjects during the performance of an innovative cognitive task, Aristotle’s valid and invalid syllogisms, and how these differences correlate with brain [...] Read more.
We aim to investigate whether EEG dynamics differ in adults with ASD (Autism Spectrum Disorders) and ADHD (attention-deficit/hyperactivity disorder) compared with healthy subjects during the performance of an innovative cognitive task, Aristotle’s valid and invalid syllogisms, and how these differences correlate with brain regions and behavioral data for each subject. We recorded EEGs from 14 scalp electrodes (channels) in 21 adults with ADHD, 21 with ASD, and 21 healthy, normal subjects. The subjects were exposed in a set of innovative cognitive tasks (inducing varying cognitive loads), Aristotle’s two types of syllogism mentioned above. A set of 39 questions were given to participants related to valid–invalid syllogisms as well as a separate set of questionnaires, in order to collect a number of demographic and behavioral data, with the aim of detecting shared information with values of a feature extracted from EEG, the multiscale entropy (MSE), in the 14 channels (‘brain regions’). MSE, a nonlinear information-theoretic measure of complexity, was computed to extract a feature that quantifies the complexity of the EEG. Behavior-Partial Least Squares Correlation, PLSC, is the method to detect the correlation between two sets of data, brain, and behavioral measures. -PLSC, a variant of PLSC, was applied to build a functional connectivity of the brain regions involved in the reasoning tasks. Graph-theoretic measures were used to quantify the complexity of the functional networks. Based on the results of the analysis described in this work, a mixed 14 × 2 × 3 ANOVA showed significant main effects of group factor and brain region* syllogism factor, as well as a significant brain region* group interaction. There are significant differences between the means of MSE (complexity) values at the 14 channels of the members of the ‘pathological’ groups of participants, i.e., between ASD and ADHD, while the difference in means of MSE between both ASD and ADHD and that of the control group is not significant. In conclusion, the valid–invalid type of syllogism generates significantly different complexity values, MSE, between ASD and ADHD. The complexity of activated brain regions of ASD participants increased significantly when switching from a valid to an invalid syllogism, indicating the need for more resources to ‘face’ the task escalating difficulty in ASD subjects. This increase is not so evident in both ADHD and control. Statistically significant differences were found also in the behavioral response of ASD and ADHD, compared with those of control subjects, based on the principal brain and behavior saliences extracted by PLSC. Specifically, two behavioral measures, the emotional state and the degree of confidence of participants in answering questions in Aristotle’s valid–invalid syllogisms, and one demographic variable, age, statistically and significantly discriminate the three groups’ ASD. The seed-PLC generated functional connectivity networks for ASD, ADHD, and control, were ‘projected’ on the regions of the Default Mode Network (DMN), the ‘reference’ connectivity, of which the structural changes were found significant in distinguishing the three groups. The contribution of this work lies in the examination of the relationship between brain activity and behavioral responses of healthy and ‘pathological’ participants in the case of cognitive reasoning of the type of Aristotle’s valid and invalid syllogisms, using PLSC, a machine learning approach combined with MSE, a nonlinear method of extracting a feature based on EEGs that captures a broad spectrum of EEGs linear and nonlinear characteristics. The results seem promising in adopting this type of reasoning, in the future, after further enhancements and experimental tests, as a supplementary instrument towards examining the differences in brain activity and behavioral responses of ASD and ADHD patients. The application of the combination of these two methods, after further elaboration and testing as new and complementary to the existing ones, may be considered as a tool of analysis in helping detecting more effectively such types of disorders. Full article
(This article belongs to the Section Behavioral Neuroscience)
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Editorial
The Emerging Role of Scalogram-Based Convolutional Neural Network in the Diagnosis of Epileptic Seizures
Brain Sci. 2021, 11(11), 1530; https://doi.org/10.3390/brainsci11111530 - 18 Nov 2021
Viewed by 208
Abstract
Epilepsy, a common disorder affecting 1–2% of the population, can significantly impact a person’s quality of life and can lead to disability or even death [...] Full article
(This article belongs to the Section Neurotechnology and Neuroimaging)
Article
Molecular and Clinical Characterization of a Novel Prognostic and Immunologic Biomarker GPSM3 in Low-Grade Gliomas
Brain Sci. 2021, 11(11), 1529; https://doi.org/10.3390/brainsci11111529 - 18 Nov 2021
Viewed by 282
Abstract
Background: as the most common malignancy of the central nervous system, low-grade glioma (LGG) patients suffered a poor prognosis. Tumor microenvironment, especially immune components, plays an important role in the progression of tumors. Thus, it is critical to explore the key immune-related genes, [...] Read more.
Background: as the most common malignancy of the central nervous system, low-grade glioma (LGG) patients suffered a poor prognosis. Tumor microenvironment, especially immune components, plays an important role in the progression of tumors. Thus, it is critical to explore the key immune-related genes, a comprehensive understanding of the TME in LGG helps us find novel cancer biomarkers and therapeutic targets. Methods: the GPSM3 expression level and the correlations between clinical characteristics and GPSM3 levels were analyzed with the data from CGGA and TCGA dataset. Univariate and multivariate cox regression model were built to predict the prognosis of LGG patients with multiple factors. Then the correlation between GPSM3 with immune cell infiltration was explored by ESTIMATE, CIBERSORT and TIMER2.0. At last, the correlation analyzed between GPSM3 expression and immune checkpoint related genes were also analyzed. Results: GPSM3 expression was overexpressed in LGG and negatively correlated to the GPSM3 DNA methylation. Univariate and multivariate Cox analysis demonstrated that GPSM3 expression was an independent prognostic factor in LGG patients. Functional characterization of GPSM3 revealed that it was associated with many immune processes to tumor cells. GPSM3 expression was positive related to the immune score, Stromal scores and ESTIMATE scores, but negative related to the Tumor purity. Immune features in the TME of GPSM3-high LGG group is characterized by a higher infiltrating of regulatory T cells, neutrophils, macrophages M2, and a lower proportion of monocytes than to the GPSM3-low group. Furthermore, GPSM3 expression exhibited significant correlations with the immune checkpoint-related genes, especially PD-1, PD-L1, PD-L2, CTLA4 and TIM3. Conclusions: these findings proved that GPSM3 could serve as a prognostic biomarker and potential immunotherapy target for LGG. Full article
(This article belongs to the Special Issue Frontiers in the Immunology of Brain Tumors)
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Article
fMRI Evidence for Default Mode Network Deactivation Associated with Rapid Eye Movements in Sleep
Brain Sci. 2021, 11(11), 1528; https://doi.org/10.3390/brainsci11111528 - 18 Nov 2021
Viewed by 558
Abstract
System-specific brain responses—time-locked to rapid eye movements (REMs) in sleep—are characteristically widespread, with robust and clear activation in the primary visual cortex and other structures involved in multisensory integration. This pattern suggests that REMs underwrite hierarchical processing of visual information in a time-locked [...] Read more.
System-specific brain responses—time-locked to rapid eye movements (REMs) in sleep—are characteristically widespread, with robust and clear activation in the primary visual cortex and other structures involved in multisensory integration. This pattern suggests that REMs underwrite hierarchical processing of visual information in a time-locked manner, where REMs index the generation and scanning of virtual-world models, through multisensory integration in dreaming—as in awake states. Default mode network (DMN) activity increases during rest and reduces during various tasks including visual perception. The implicit anticorrelation between the DMN and task-positive network (TPN)—that persists in REM sleep—prompted us to focus on DMN responses to temporally-precise REM events. We timed REMs during sleep from the video recordings and quantified the neural correlates of REMs—using functional MRI (fMRI)—in 24 independent studies of 11 healthy participants. A reanalysis of these data revealed that the cortical areas exempt from widespread REM-locked brain activation were restricted to the DMN. Furthermore, our analysis revealed a modest temporally-precise REM-locked decrease—phasic deactivation—in key DMN nodes, in a subset of independent studies. These results are consistent with hierarchical predictive coding; namely, permissive deactivation of DMN at the top of the hierarchy (leading to the widespread cortical activation at lower levels; especially the primary visual cortex). Additional findings indicate REM-locked cerebral vasodilation and suggest putative mechanisms for dream forgetting. Full article
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Article
Testing the Foreign Language Effect on Cognitive Reflection in Older Adults
Brain Sci. 2021, 11(11), 1527; https://doi.org/10.3390/brainsci11111527 - 18 Nov 2021
Viewed by 289
Abstract
An increasing number of people around the world communicate in more than one language, resulting in them having to make decisions in a foreign language on a daily basis. Interestingly, a burgeoning body of literature suggests that people’s decision-making is affected by whether [...] Read more.
An increasing number of people around the world communicate in more than one language, resulting in them having to make decisions in a foreign language on a daily basis. Interestingly, a burgeoning body of literature suggests that people’s decision-making is affected by whether they are reasoning in their native language (NL) or their foreign language (FL). According to the foreign language effect (FLe), people are less susceptible to bias in many decision-making tasks and more likely to display utilitarian cost-benefit analysis in moral decision-making when reasoning in a FL. While these differences have often been attributed to a reduced emotionality in the FL, an emerging body of literature has started to test the extent to which these could be attributable to increased deliberation in the FL. The present study tests whether increased deliberation leads to a FLe on cognitive reflection in a population of older adults (Mage = 65.1), from the successful aging project in Umeå, Sweden. We explored whether performance on a 6-item version of the cognitive reflection test (CRT) adapted to Swedish would differ between participants for whom Swedish was their NL and those for whom Swedish was their FL. The CRT is a task designed to elicit an incorrect, intuitive answer. In order to override the intuitive answer, one requires engaging in deliberative, analytical thinking to determine the correct answer. Therefore, we hypothesized that if thinking in a FL increases deliberation, then those performing the task in their FL would exhibit higher accuracy rates than those performing in their NL. Our results showed that age and level of education predicted performance on the task but performance on the CRT did not differ between the NL and the FL groups. In addition, in the FL group, proficiency in the FL was not related to performance in the CRT. Our results, therefore, do not provide evidence that thinking in a FL increases deliberation in a group of older adults performing a logical reasoning task that is not typically associated with an emotional connotation. Full article
(This article belongs to the Special Issue Neurocognitive Underpinnings of the Foreign Language Effect)
Review
The Role of Expectation and Beliefs on the Effects of Non-Invasive Brain Stimulation
Brain Sci. 2021, 11(11), 1526; https://doi.org/10.3390/brainsci11111526 - 18 Nov 2021
Viewed by 392
Abstract
Non-invasive brain stimulation (NIBS) techniques are used in clinical and cognitive neuroscience to induce a mild magnetic or electric field in the brain to modulate behavior and cortical activation. Despite the great body of literature demonstrating promising results, unexpected or even paradoxical outcomes [...] Read more.
Non-invasive brain stimulation (NIBS) techniques are used in clinical and cognitive neuroscience to induce a mild magnetic or electric field in the brain to modulate behavior and cortical activation. Despite the great body of literature demonstrating promising results, unexpected or even paradoxical outcomes are sometimes observed. This might be due either to technical and methodological issues (e.g., stimulation parameters, stimulated brain area), or to participants’ expectations and beliefs before and during the stimulation sessions. In this narrative review, we present some studies showing that placebo and nocebo effects, associated with positive and negative expectations, respectively, could be present in NIBS trials, both in experimental and in clinical settings. The lack of systematic evaluation of subjective expectations and beliefs before and after stimulation could represent a caveat that overshadows the potential contribution of placebo and nocebo effects in the outcome of NIBS trials. Full article
Systematic Review
Neural Decoding of EEG Signals with Machine Learning: A Systematic Review
Brain Sci. 2021, 11(11), 1525; https://doi.org/10.3390/brainsci11111525 - 18 Nov 2021
Viewed by 408
Abstract
Electroencephalography (EEG) is a non-invasive technique used to record the brain’s evoked and induced electrical activity from the scalp. Artificial intelligence, particularly machine learning (ML) and deep learning (DL) algorithms, are increasingly being applied to EEG data for pattern analysis, group membership classification, [...] Read more.
Electroencephalography (EEG) is a non-invasive technique used to record the brain’s evoked and induced electrical activity from the scalp. Artificial intelligence, particularly machine learning (ML) and deep learning (DL) algorithms, are increasingly being applied to EEG data for pattern analysis, group membership classification, and brain-computer interface purposes. This study aimed to systematically review recent advances in ML and DL supervised models for decoding and classifying EEG signals. Moreover, this article provides a comprehensive review of the state-of-the-art techniques used for EEG signal preprocessing and feature extraction. To this end, several academic databases were searched to explore relevant studies from the year 2000 to the present. Our results showed that the application of ML and DL in both mental workload and motor imagery tasks has received substantial attention in recent years. A total of 75% of DL studies applied convolutional neural networks with various learning algorithms, and 36% of ML studies achieved competitive accuracy by using a support vector machine algorithm. Wavelet transform was found to be the most common feature extraction method used for all types of tasks. We further examined the specific feature extraction methods and end classifier recommendations discovered in this systematic review. Full article
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Article
In Time with the Beat: Entrainment in Patients with Phonological Impairment, Apraxia of Speech, and Parkinson’s Disease
Brain Sci. 2021, 11(11), 1524; https://doi.org/10.3390/brainsci11111524 - 18 Nov 2021
Viewed by 397
Abstract
In the present study, we investigated if individuals with neurogenic speech sound impairments of three types, Parkinson’s dysarthria, apraxia of speech, and aphasic phonological impairment, accommodate their speech to the natural speech rhythm of an auditory model, and if so, whether the effect [...] Read more.
In the present study, we investigated if individuals with neurogenic speech sound impairments of three types, Parkinson’s dysarthria, apraxia of speech, and aphasic phonological impairment, accommodate their speech to the natural speech rhythm of an auditory model, and if so, whether the effect is more significant after hearing metrically regular sentences as compared to those with an irregular pattern. This question builds on theories of rhythmic entrainment, assuming that sensorimotor predictions of upcoming events allow humans to synchronize their actions with an external rhythm. To investigate entrainment effects, we conducted a sentence completion task relating participants’ response latencies to the spoken rhythm of the prime heard immediately before. A further research question was if the perceived rhythm interacts with the rhythm of the participants’ own productions, i.e., the trochaic or iambic stress pattern of disyllabic target words. For a control group of healthy speakers, our study revealed evidence for entrainment when trochaic target words were preceded by regularly stressed prime sentences. Persons with Parkinson’s dysarthria showed a pattern similar to that of the healthy individuals. For the patient groups with apraxia of speech and with phonological impairment, considerably longer response latencies with differing patterns were observed. Trochaic target words were initiated with significantly shorter latencies, whereas the metrical regularity of prime sentences had no consistent impact on response latencies and did not interact with the stress pattern of the target words to be produced. The absence of an entrainment in these patients may be explained by the more severe difficulties in initiating speech at all. We discuss the results in terms of clinical implications for diagnostics and therapy in neurogenic speech disorders. Full article
(This article belongs to the Special Issue Motor Speech Disorders and Prosody)
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Article
Implicit Associations between Adverbs of Place and Actions in the Physical and Digital Space
Brain Sci. 2021, 11(11), 1523; https://doi.org/10.3390/brainsci11111523 - 17 Nov 2021
Viewed by 462
Abstract
Neuropsychological, behavioral, and neurophysiological evidence indicates that the coding of space as near and far depends on the involvement of different neuronal circuits. These circuits are recruited on the basis of functional parameters, not of metrical ones, reflecting a general distinction of human [...] Read more.
Neuropsychological, behavioral, and neurophysiological evidence indicates that the coding of space as near and far depends on the involvement of different neuronal circuits. These circuits are recruited on the basis of functional parameters, not of metrical ones, reflecting a general distinction of human behavior, which alternatively attributes to the individual the role of agent or observer. Although much research in cognitive psychology was devoted to demonstrating that language and concepts are rooted in the sensorimotor system, no study has investigated the presence of implicit associations between different adverbs of place (far vs. near) and actions with different functional characteristics. Using a series of Implicit Association Test (IAT) experiments, we tested this possibility for both actions performed in physical space (grasp vs. look at) and those performed when using digital technology (content generation vs. content consumption). For both the physical and digital environments, the results showed an association between the adverb near and actions related to the role of agent, and between the adverb far and actions related to the role of observer. Present findings are the first experimental evidence of an implicit association between different adverbs of place and different actions and of the fact that adverbs of place also apply to the digital environment. Full article
(This article belongs to the Special Issue The Role of the Sensorimotor System in Cognitive Functions)
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Article
Love Stinks: The Association between Body Odors and Romantic Relationship Commitment
Brain Sci. 2021, 11(11), 1522; https://doi.org/10.3390/brainsci11111522 - 17 Nov 2021
Viewed by 364
Abstract
Anecdotal reports indicate that women dislike their partner’s body odor (BO) during the breakdown of a relationship; however, whether disliking a partner’s BO is associated with intentions to break up has not been empirically tested. Therefore, the aim of the current study was [...] Read more.
Anecdotal reports indicate that women dislike their partner’s body odor (BO) during the breakdown of a relationship; however, whether disliking a partner’s BO is associated with intentions to break up has not been empirically tested. Therefore, the aim of the current study was to investigate, for the first time, whether disliking one’s partner’s BOs is associated with experiencing lower commitment to a romantic relationship. Eighty participants (48 partnered, 32 single and previously partnered) completed self-report questionnaires about their current or previous romantic relationship and the amount of exposure to—and hedonic ratings of—their current or former partner’s BOs. Olfactory function was also tested, and participants smelled and rated various pieces of clothing imbued with a stranger’s BO. The results demonstrated that for participants who had experienced a breakup, historically higher levels of relationship commitment were associated with higher hedonic ratings of a previous partner’s BOs, regardless of the type of BOs. For participants currently in a relationship, lower relationship commitment was associated with higher breakup intentions in response to smelling their partner’s BOs. These preliminary results contribute evidence for the positive association between exposure to a partner’s BOs and favorable hedonic appraisals of BOs; however, further research needs to be conducted in this area to investigate nuances. Lower levels of exposure to one’s partner’s BOs may be more indicative of relationship commitment than exposure to hedonically unpleasant BOs of one’s partner. The findings are discussed with reference to their implications for interventions in relationship breakdown. Full article
Article
Serum Vitamin D as a Marker of Impaired Information Processing Speed and Early Disability in Multiple Sclerosis Patients
Brain Sci. 2021, 11(11), 1521; https://doi.org/10.3390/brainsci11111521 - 17 Nov 2021
Viewed by 278
Abstract
Slowed information processing speed (IPS) is the hallmark and first cognitive domain to be altered in multiple sclerosis (MS) patients. Insufficient serum vitamin D was previously associated with disease development, relapses, and progression, but little is reported on cognition. However, vitamin D and [...] Read more.
Slowed information processing speed (IPS) is the hallmark and first cognitive domain to be altered in multiple sclerosis (MS) patients. Insufficient serum vitamin D was previously associated with disease development, relapses, and progression, but little is reported on cognition. However, vitamin D and cognitive impairment (CI) in other neurodegenerative diseases have already been linked. We explored the possible correlation between vitamin D and IPS at diagnosis and early disability at last follow-up in 81 MS patients. At diagnosis, we collected vitamin D levels and performed a Symbol Digit Modalities Test (SDMT). Raw scores were adjusted for age, gender, and educational level. Early disability was evaluated with MS severity score (MSSS) and age-related MSSS (ARMSS). A total of 71 patients (86.58%) showed hypovitaminosis D (19.71 ± 8.76 ng/mL) and 18 patients (21.95%) had CI. Patients with CI showed severe hypovitaminosis D (p = 0.004). No patients with sufficient vitamin D levels had CI. We found a positive correlation between vitamin D levels at diagnosis and (1) SDMT raw and z-score that persisted after correction for sunlight exposure and MRI baseline characteristics, and (2) EDSS, MSSS, and ARMSS after a mean 2 year follow-up. Low vitamin D levels may affect both cognition and early disability in newly diagnosed MS patients. Full article
(This article belongs to the Special Issue Cognitive Involvement in Multiple Sclerosis)
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Article
Persistence of the Effects of the COVID-19 Lockdown on Sleep: A Longitudinal Study
Brain Sci. 2021, 11(11), 1520; https://doi.org/10.3390/brainsci11111520 - 17 Nov 2021
Viewed by 445
Abstract
The effects of the COVID-19 pandemic on sleep have been widely documented, but longitudinal evaluations during different phases of the “COVID-19 era” are needed to disentangle the specific consequences of the r145estrictive measures on sleep variables. The aim of this study was to [...] Read more.
The effects of the COVID-19 pandemic on sleep have been widely documented, but longitudinal evaluations during different phases of the “COVID-19 era” are needed to disentangle the specific consequences of the r145estrictive measures on sleep variables. The aim of this study was to assess the immediate effect of the lockdown’s end on sleep and sleep-related dimensions in an Italian sample, also considering the stress and depressive symptoms. We used an online survey to longitudinally collect data on sociodemographic, environmental, clinical, sleep, and sleep-related variables in two time points: during and immediately after the lockdown. The final sample included 102 participants. The large prevalence of poor sleep quality, clinically relevant pre-sleep arousal, and depressive symptoms, as well as poor sleep quality and pre-sleep arousal score observed during the lockdown, remained stable after its end. On the other hand, the prevalence of moderate-to-severe event-related stress and intrusive symptom scores exhibited a drastic reduction after the end of home confinement. Both bedtime and rise time were anticipated after the lockdown, while sleep quality exhibited only a trend of post-lockdown sleep disturbance reduction. Our findings point to a reduced stress level (specific for the intrusive symptomatology) after the end of the lockdown and persistence of sleep problems, suggesting two non-mutually exclusive hypotheses: (a) the strict restrictive measures are not the main cause of sleep problems during the pandemic and (b) home confinement induces long-lasting effects on sleep observable after its end, and a longer period of time might be needed to observe an improvement. Full article
(This article belongs to the Special Issue Sleep Disorders and COVID-19)
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Review
Digital Biomarkers in Multiple Sclerosis
Brain Sci. 2021, 11(11), 1519; https://doi.org/10.3390/brainsci11111519 - 16 Nov 2021
Viewed by 560
Abstract
For incurable diseases, such as multiple sclerosis (MS), the prevention of progression and the preservation of quality of life play a crucial role over the entire therapy period. In MS, patients tend to become ill at a younger age and are so variable [...] Read more.
For incurable diseases, such as multiple sclerosis (MS), the prevention of progression and the preservation of quality of life play a crucial role over the entire therapy period. In MS, patients tend to become ill at a younger age and are so variable in terms of their disease course that there is no standard therapy. Therefore, it is necessary to enable a therapy that is as personalized as possible and to respond promptly to any changes, whether with noticeable symptoms or symptomless. Here, measurable parameters of biological processes can be used, which provide good information with regard to prognostic and diagnostic aspects, disease activity and response to therapy, so-called biomarkers Increasing digitalization and the availability of easy-to-use devices and technology also enable healthcare professionals to use a new class of digital biomarkers—digital health technologies—to explain, influence and/or predict health-related outcomes. The technology and devices from which these digital biomarkers stem are quite broad, and range from wearables that collect patients’ activity during digitalized functional tests (e.g., the Multiple Sclerosis Performance Test, dual-tasking performance and speech) to digitalized diagnostic procedures (e.g., optical coherence tomography) and software-supported magnetic resonance imaging evaluation. These technologies offer a timesaving way to collect valuable data on a regular basis over a long period of time, not only once or twice a year during patients’ routine visit at the clinic. Therefore, they lead to real-life data acquisition, closer patient monitoring and thus a patient dataset useful for precision medicine. Despite the great benefit of such increasing digitalization, for now, the path to implementing digital biomarkers is widely unknown or inconsistent. Challenges around validation, infrastructure, evidence generation, consistent data collection and analysis still persist. In this narrative review, we explore existing and future opportunities to capture clinical digital biomarkers in the care of people with MS, which may lead to a digital twin of the patient. To do this, we searched published papers for existing opportunities to capture clinical digital biomarkers for different functional systems in the context of MS, and also gathered perspectives on digital biomarkers under development or already existing as a research approach. Full article
(This article belongs to the Special Issue Digital innovation in Multiple Sclerosis Management)
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