Brain Sciences

12 pages, 237 KiB

Open AccessArticle

Driving After Drinking Alcohol Associated with Insufficient Sleep and Insomnia among Student Athletes and Non-Athletes

by Celyne H. Bastien, Jason G. Ellis, Amy Athey, Subhajit Chakravorty, Rebecca Robbins, Adam P. Knowlden, Jonathan Charest and Michael A. Grandner

Brain Sci. 2019, 9(2), 46; https://doi.org/10.3390/brainsci9020046 - 20 Feb 2019

Cited by 5 | Viewed by 5529

Abstract

Introduction: The proportion of university/college students (UCS) consuming alcohol is similar to the number of those reporting poor sleep, at approximately 30%, the proportion being greater in student athletes (SA). What remains to be understood is if poor sleep potentiates risky behaviors. Objective: [...] Read more.

Introduction: The proportion of university/college students (UCS) consuming alcohol is similar to the number of those reporting poor sleep, at approximately 30%, the proportion being greater in student athletes (SA). What remains to be understood is if poor sleep potentiates risky behaviors. Objective: Our aim was to examine the association among sleep difficulties, insomnia symptoms, and insufficient sleep on the risk of driving under the influence of alcohol in a sample of UCS and whether these associations were more pertinent in SA. Methods: Data from the National University/College Health Assessment was used from the years 2011–2014. Questions on number of drinks consumed and behaviors such as driving after drinking alcohol were related to answers to questions pertaining to sleep difficulties, insufficient sleep, and insomnia symptoms. Results: Mean alcohol intake was of about 3 drinks; SA consumed significantly more than student non-athletes (SNA). Binge-drinking episodes were significantly higher among SA than SNA. Difficulty sleeping was associated with an increased likelihood of driving after any drinks and after 5 or more drinks in both groups, effects being stronger among SA. Insomnia was associated with an increased likelihood of driving after any drinks and after 5 or more drinks in SA and after 5 or more drinks in SNA. These effects were stronger among athletes. Conclusion: The present study found that self-reported difficulties sleeping, insomnia symptoms, and insufficient sleep are associated with driving after drinking alcohol. This relationship applied to driving after drinking any alcohol or binge drinking and was again stronger among SA than SNA. Full article

(This article belongs to the Special Issue Insomnia: Beyond Hyperarousal)

12 pages, 970 KiB

Open AccessReview

Neuromodulation Strategies in Post-Traumatic Stress Disorder: From Preclinical Models to Clinical Applications

by Flavia V. Gouveia, Darryl C. Gidyk, Peter Giacobbe, Enoch Ng, Ying Meng, Benjamin Davidson, Agessandro Abrahao, Nir Lipsman and Clement Hamani

Brain Sci. 2019, 9(2), 45; https://doi.org/10.3390/brainsci9020045 - 19 Feb 2019

Cited by 22 | Viewed by 7557

Abstract

Post-traumatic stress disorder (PTSD) is an often debilitating disease with a lifetime prevalence rate between 5–8%. In war veterans, these numbers are even higher, reaching approximately 10% to 25%. Although most patients benefit from the use of medications and psychotherapy, approximately 20% to [...] Read more.

Post-traumatic stress disorder (PTSD) is an often debilitating disease with a lifetime prevalence rate between 5–8%. In war veterans, these numbers are even higher, reaching approximately 10% to 25%. Although most patients benefit from the use of medications and psychotherapy, approximately 20% to 30% do not have an adequate response to conventional treatments. Neuromodulation strategies have been investigated for various psychiatric disorders with promising results, and may represent an important treatment option for individuals with difficult-to-treat forms of PTSD. We review the relevant neurocircuitry and preclinical stimulation studies in models of fear and anxiety, as well as clinical data on the use of transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), and deep brain stimulation (DBS) for the treatment of PTSD. Full article

(This article belongs to the Special Issue Neurobiology of Fear: From Basic Mechanisms to Therapeutic Approaches)

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10 pages, 1018 KiB

Open AccessArticle

Awake Testing during Deep Brain Stimulation Surgery Predicts Postoperative Stimulation Side Effect Thresholds

by Harrison C. Walker, Jesse Faulk, AKM Fazlur Rahman, Christopher L. Gonzalez, Patrick Roush, Arie Nakhmani, Jason L. Crowell and Barton L. Guthrie

Brain Sci. 2019, 9(2), 44; https://doi.org/10.3390/brainsci9020044 - 18 Feb 2019

Cited by 11 | Viewed by 4900

Abstract

Despite substantial experience with deep brain stimulation for movement disorders and recent interest in electrode targeting under general anesthesia, little is known about whether awake macrostimulation during electrode targeting predicts postoperative side effects from stimulation. We hypothesized that intraoperative awake macrostimulation with the [...] Read more.

Despite substantial experience with deep brain stimulation for movement disorders and recent interest in electrode targeting under general anesthesia, little is known about whether awake macrostimulation during electrode targeting predicts postoperative side effects from stimulation. We hypothesized that intraoperative awake macrostimulation with the newly implanted DBS lead predicts dose-limiting side effects during device activation in clinic. We reviewed 384 electrode implants for movement disorders, characterized the presence or absence of stimulus amplitude thresholds for dose-limiting DBS side effects during surgery, and measured their predictive value for side effects during device activation in clinic with odds ratios ±95% confidence intervals. We also estimated associations between voltage thresholds for side effects within participants. Intraoperative clinical response to macrostimulation led to adjustments in DBS electrode position during surgery in 37.5% of cases (31.0% adjustment of lead depth, 18.2% new trajectory, or 11.7% both). Within and across targets and disease states, dose-limiting stimulation side effects from the final electrode position in surgery predict postoperative side effects, and side effect thresholds in clinic occur at lower stimulus amplitudes versus those encountered in surgery. In conclusion, awake clinical testing during DBS targeting impacts surgical decision-making and predicts dose-limiting side effects during subsequent device activation. Full article

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11 pages, 14362 KiB

Open AccessArticle

A Functional NIRS Study of Brain Functional Networks Induced by Social Time Coordination

by Megumi Mizuno, Tomoyuki Hiroyasu and Satoru Hiwa

Brain Sci. 2019, 9(2), 43; https://doi.org/10.3390/brainsci9020043 - 15 Feb 2019

Cited by 3 | Viewed by 6058

Abstract

The ability to coordinate one’s behavior with the others’ behavior is essential to achieve a joint action in daily life. In this paper, the brain activity during synchronized tapping task was measured using functional near infrared spectroscopy (fNIRS) to investigate the relationship between [...] Read more.

The ability to coordinate one’s behavior with the others’ behavior is essential to achieve a joint action in daily life. In this paper, the brain activity during synchronized tapping task was measured using functional near infrared spectroscopy (fNIRS) to investigate the relationship between time coordination and brain function. Furthermore, using brain functional network analysis based on graph theory, we examined important brain regions and network structures that serve as the hub when performing the synchronized tapping task. Using the data clustering method, two types of brain function networks were extracted and associated with time coordination, suggesting that they were involved in expectation and imitation behaviors. Full article

(This article belongs to the Special Issue Collection on Cognitive Neuroscience)

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19 pages, 767 KiB

Open AccessReview

The Contribution of Pluripotent Stem Cell (PSC)-Based Models to the Study of Fragile X Syndrome (FXS)

by Manar Abu Diab and Rachel Eiges

Brain Sci. 2019, 9(2), 42; https://doi.org/10.3390/brainsci9020042 - 15 Feb 2019

Cited by 8 | Viewed by 5975

Abstract

Fragile X syndrome (FXS) is the most common heritable form of cognitive impairment. It results from a deficiency in the fragile X mental retardation protein (FMRP) due to a CGG repeat expansion in the 5′-UTR of the X-linked FMR1 gene. When CGGs expand [...] Read more.

Fragile X syndrome (FXS) is the most common heritable form of cognitive impairment. It results from a deficiency in the fragile X mental retardation protein (FMRP) due to a CGG repeat expansion in the 5′-UTR of the X-linked FMR1 gene. When CGGs expand beyond 200 copies, they lead to epigenetic gene silencing of the gene. In addition, the greater the allele size, the more likely it will become unstable and exhibit mosaicism for expansion size between and within tissues in affected individuals. The timing and mechanisms of FMR1 epigenetic gene silencing and repeat instability are far from being understood given the lack of appropriate cellular and animal models that can fully recapitulate the molecular features characteristic of the disease pathogenesis in humans. This review summarizes the data collected to date from mutant human embryonic stem cells, induced pluripotent stem cells, and hybrid fusions, and discusses their contribution to the investigation of FXS, their key limitations, and future prospects. Full article

(This article belongs to the Special Issue Towards Mechanism-based Treatments for Fragile X Syndrome)

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10 pages, 1716 KiB

Open AccessArticle

Corticospinal Excitability to the Biceps Brachii is Not Different When Arm Cycling at a Self-Selected or Fixed Cadence

by Evan J. Lockyer, Anna P. Nippard, Kaitlyn Kean, Nicole Hollohan, Duane C. Button and Kevin E. Power

Brain Sci. 2019, 9(2), 41; https://doi.org/10.3390/brainsci9020041 - 14 Feb 2019

Cited by 7 | Viewed by 4430

Abstract

Background: The present study compared corticospinal excitability to the biceps brachii muscle during arm cycling at a self-selected and a fixed cadence (SSC and FC, respectively). We hypothesized that corticospinal excitability would not be different between the two conditions. Methods: The SSC was [...] Read more.

Background: The present study compared corticospinal excitability to the biceps brachii muscle during arm cycling at a self-selected and a fixed cadence (SSC and FC, respectively). We hypothesized that corticospinal excitability would not be different between the two conditions. Methods: The SSC was initially performed and the cycling cadence was recorded every 5 s for one minute. The average cadence of the SSC cycling trial was then used as a target for the FC of cycling that the participants were instructed to maintain. The motor evoked potentials (MEPs) elicited via transcranial magnetic stimulation (TMS) of the motor cortex were recorded from the biceps brachii during each trial of SSC and FC arm cycling. Results: Corticospinal excitability, as assessed via normalized MEP amplitudes (MEPs were made relative to a maximal compound muscle action potential), was not different between groups. Conclusions: Focusing on maintaining a fixed cadence during arm cycling does not influence corticospinal excitability, as assessed via TMS-evoked MEPs. Full article

(This article belongs to the Special Issue Neurophysiological Correlates to Behavioural Performance in Motor Learning)

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28 pages, 12988 KiB

Open AccessArticle

Bilingual and Monolingual First Language Acquisition Experience Differentially Shapes Children’s Property Term Learning: Evidence from Behavioral and Neurophysiological Measures

by Agnes Groba, Annick De Houwer, Hellmuth Obrig and Sonja Rossi

Brain Sci. 2019, 9(2), 40; https://doi.org/10.3390/brainsci9020040 - 12 Feb 2019

Cited by 6 | Viewed by 7324

Abstract

Studies of novel noun learning show bilingual children rely less on the Mutual Exclusivity Constraint (MEC) for word learning than monolinguals. Shifting the focus to learning novel property terms (adjectives), the present study compared 3.5- and five-year-old bilingual and monolingual preschoolers’ adherence to [...] Read more.

Studies of novel noun learning show bilingual children rely less on the Mutual Exclusivity Constraint (MEC) for word learning than monolinguals. Shifting the focus to learning novel property terms (adjectives), the present study compared 3.5- and five-year-old bilingual and monolingual preschoolers’ adherence to the MEC. We found no bilingual-monolingual differences on a behavioral forced-choice task for the 3.5-year-olds, but five-year-old monolinguals adhered more to the MEC than bilinguals did. Older bilinguals adhered less to the MEC than younger ones, while there was no difference in MEC adherence between the younger and older monolinguals. In the 5-year-olds, we additionally acquired neurophysiological data using functional near-infrared spectroscopy (fNIRS) to allow for a first explorative look at potential neuronal underpinnings. The data show that, compared to bilinguals, monolinguals reveal higher activation over three brain regions (right frontal, left temporo-parietal, and left prefrontal) that may be involved in exploiting the MEC, building on conflict detection, inhibition, solution of a disjunction, and working memory processes. Taken together, our behavioral and neurophysiological findings reveal different paths towards novel property term learning depending on children’s language acquisition context. Full article

(This article belongs to the Special Issue Cognitive Neuroscience of Cross-Language Interaction in Bilinguals)

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18 pages, 1010 KiB

Open AccessReview

Pharmacological Reactivation of the Silenced FMR1 Gene as a Targeted Therapeutic Approach for Fragile X Syndrome

by Daman Kumari, Inbal Gazy and Karen Usdin

Brain Sci. 2019, 9(2), 39; https://doi.org/10.3390/brainsci9020039 - 12 Feb 2019

Cited by 14 | Viewed by 6960

Abstract

More than ~200 CGG repeats in the 5′ untranslated region of the FMR1 gene results in transcriptional silencing and the absence of the FMR1 encoded protein, FMRP. FMRP is an RNA-binding protein that regulates the transport and translation of a variety of brain [...] Read more.

More than ~200 CGG repeats in the 5′ untranslated region of the FMR1 gene results in transcriptional silencing and the absence of the FMR1 encoded protein, FMRP. FMRP is an RNA-binding protein that regulates the transport and translation of a variety of brain mRNAs in an activity-dependent manner. The loss of FMRP causes dysregulation of many neuronal pathways and results in an intellectual disability disorder, fragile X syndrome (FXS). Currently, there is no effective treatment for FXS. In this review, we discuss reactivation of the FMR1 gene as a potential approach for FXS treatment with an emphasis on the use of small molecules to inhibit the pathways important for gene silencing. Full article

(This article belongs to the Special Issue Towards Mechanism-based Treatments for Fragile X Syndrome)

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16 pages, 1682 KiB

Open AccessArticle

Working Memory, Cognitive Load and Cardiorespiratory Fitness: Testing the CRUNCH Model with Near-Infrared Spectroscopy

by Nounagnon Frutueux Agbangla, Michel Audiffren, Jean Pylouster and Cédric T. Albinet

Brain Sci. 2019, 9(2), 38; https://doi.org/10.3390/brainsci9020038 - 9 Feb 2019

Cited by 29 | Viewed by 7431

Abstract

The present study aimed to examine the effects of chronological age and cardiorespiratory fitness (CRF) on cognitive performance and prefrontal cortex activity, and to test the compensation-related utilization of neural circuits hypothesis (CRUNCH). A total of 19 young adults (18–22 years) and 37 [...] Read more.

The present study aimed to examine the effects of chronological age and cardiorespiratory fitness (CRF) on cognitive performance and prefrontal cortex activity, and to test the compensation-related utilization of neural circuits hypothesis (CRUNCH). A total of 19 young adults (18–22 years) and 37 older ones (60–77 years) with a high or low CRF level were recruited to perform a working memory updating task under three different cognitive load conditions. Prefrontal cortex hemodynamic responses were continuously recorded using functional near-infrared spectroscopy, and behavioral performances and perceived difficulty were measured. Results showed that chronological age had deleterious effects on both cognitive performance and prefrontal cortex activation under a higher cognitive load. In older adults, however, higher levels of CRF were related to increased bilateral prefrontal cortex activation patterns that allowed them to sustain better cognitive performances, especially under the highest cognitive load. These results are discussed in the light of the neurocognitive CRUNCH model. Full article

(This article belongs to the Special Issue Exercising against Age-Effects on the Brain)

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13 pages, 424 KiB

Open AccessArticle

Assessment and Management of HIV-Associated Cognitive Impairment: Experience from a Multidisciplinary Memory Service for People Living with HIV

by Kate Alford, Sube Banerjee, Eileen Nixon, Clara O’Brien, Olivia Pounds, Andrew Butler, Claire Elphick, Phillip Henshaw, Stuart Anderson and Jaime H. Vera

Brain Sci. 2019, 9(2), 37; https://doi.org/10.3390/brainsci9020037 - 8 Feb 2019

Cited by 24 | Viewed by 7421

Abstract

As the HIV population ages, the prevalence of cognitive impairment (CI) is increasing, yet few services exist for the assessment and management of these individuals. Here we provide an initial description of a memory assessment service for people living with HIV and present [...] Read more.

As the HIV population ages, the prevalence of cognitive impairment (CI) is increasing, yet few services exist for the assessment and management of these individuals. Here we provide an initial description of a memory assessment service for people living with HIV and present data from a service evaluation undertaken in the clinic. We conducted an evaluation of the first 52 patients seen by the clinic. We present patient demographic data, assessment outcomes, diagnoses given and interventions delivered to those seen in the clinic. 41 patients (79%) of those seen in the clinic had objective CI: 16 (31%) met criteria for HIV-associated Neurocognitive Disorder (HAND), 2 (4%) were diagnosed with dementia, 14 (27%) showed CI associated with mental illness and/or drugs/alcohol, 7 (13%) had CI which was attributed to factors other than HIV and in 2 (4%) patients the cause remains unclear. 32 (62%) patients showed some abnormality on Magnetic Resonance Imaging (MRI) brain scans. Patients attending the clinic performed significantly worse than normative scores on all tests of global cognition and executive function. Interventions offered to patients included combination antiretroviral therapy modification, signposting to other services, case management, further health investigations and in-clinic advice. Our experience suggests that the need exists for specialist HIV memory services and that such a model of working can be successfully implemented into HIV patient care. Further work is needed on referral criteria and pathways. Diagnostic processes and treatment offered needs to consider and address the multifactorial aetiology of CI in HIV and this is essential for effective assessment and management. Full article

(This article belongs to the Special Issue Update on HIV-Associated Neurocognitive Disorders (HAND))

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17 pages, 324 KiB

Open AccessReview

Shared Neural Correlates Underlying Addictive Disorders and Negative Urgency

by Miji Um, Zachary T. Whitt, Rebecca Revilla, Taylor Hunton and Melissa A. Cyders

Brain Sci. 2019, 9(2), 36; https://doi.org/10.3390/brainsci9020036 - 8 Feb 2019

Cited by 31 | Viewed by 5420

Abstract

Negative urgency is a personality trait reflecting the tendency to act rashly in response to extreme negative emotions and is considered a transdiagnostic endophenotype for problematic levels of addictive behaviors. Recent research has begun to identify the neural correlates of negative urgency, many [...] Read more.

Negative urgency is a personality trait reflecting the tendency to act rashly in response to extreme negative emotions and is considered a transdiagnostic endophenotype for problematic levels of addictive behaviors. Recent research has begun to identify the neural correlates of negative urgency, many of which appear to overlap with neural circuitry underlying addictive disorders associated with negative urgency. The goal of this qualitative review is to summarize the extant literature concerning the neural correlates of negative urgency, to compare these correlates with those implicated with addictive disorders, and to propose new ways to begin to leverage such findings in treatment and intervention approaches. We also address current limitations in the field and make recommendations for areas for future growth in this research domain. Patterns of structure and function in the ventral striatum, frontal regions, such as the prefrontal cortex (PFC) and orbitofrontal cortex (OFC), and amygdala are common across addictive disorders and are related to both real-world risky behaviors and self-report measures of negative urgency. We propose that the time has come to move past considering this trait and these disorders as completely separate entities, and instead for the field to consider how general patterns of convergence across these disorders can lead to a more transdiagnostic approach to treatment and intervention. We suggest future work utilize these convergent patterns in the development of animal models of negative urgency, in the identification and testing of prime pharmacological and physiological interventions, and as objective biomarkers to be used when testing behavioral, pharmacological, and physiological intervention effectiveness. Little empirical work has been done to date in these areas and advances in these nascent fields would advance understanding and applications of the neuroscience of negative urgency. Full article

(This article belongs to the Special Issue Underlying Neurobiological and Neurocognitive Mechanisms of Impulsivity in Risk-Taking Behaviors)

15 pages, 1022 KiB

Open AccessBrief Report

Dunn’s Model of Sensory Processing: An Investigation of the Axes of the Four-Quadrant Model in Healthy Adults

by Alexia E. Metz, Daniella Boling, Ashley DeVore, Holly Holladay, Jo Fu Liao and Karen Vander Vlutch

Brain Sci. 2019, 9(2), 35; https://doi.org/10.3390/brainsci9020035 - 7 Feb 2019

Cited by 25 | Viewed by 11019

Abstract

We examined the behavioral response (BR) and threshold (T) axes of Dunn’s four-quadrant model of sensory processing (1997). We assessed whether they are ordinal ranges and if variation is associated with other similarly described characteristics: Introversion/Extraversion (I/E) of Eysenck’s personality model (Sato, 2005), [...] Read more.

We examined the behavioral response (BR) and threshold (T) axes of Dunn’s four-quadrant model of sensory processing (1997). We assessed whether they are ordinal ranges and if variation is associated with other similarly described characteristics: Introversion/Extraversion (I/E) of Eysenck’s personality model (Sato, 2005), and somatosensory event related potentials (SERP) and their gating (Davies & Gavin, 2007). From healthy adults (n = 139), we obtained: Adult/Adolescent Profile (A/ASP, Brown & Dunn, 2002) and Eysenck’s Personality Questionnaire, Brief Version (Sato, 2005) scores and peak amplitude and gating factor of SERP P50. We found that BR scores did not differ across normative categories of the A/ASP, but T scores significantly increased along the axis. I/E scores did not vary with BR scores. There were no differences or correlations in P50 amplitudes and gating with T scores. The findings suggest that the BR axis may not reflect a construct with ordinal range, but the T axis may. Dunn’s concept of BR appears to be distinct from Eysenck’s concept of I/E. SERP and its gating may not be directly reflective of sensory processing thresholds in healthy adults. Conclusions are limited by having few participants with passive behavior regulation or low threshold patterns of processing. Full article

(This article belongs to the Special Issue Brain Mechanisms of Sensory Processing Disorder)

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21 pages, 2171 KiB

Open AccessReview

The Role of Movement Analysis in Diagnosing and Monitoring Neurodegenerative Conditions: Insights from Gait and Postural Control

by Christopher Buckley, Lisa Alcock, Ríona McArdle, Rana Zia Ur Rehman, Silvia Del Din, Claudia Mazzà, Alison J. Yarnall and Lynn Rochester

Brain Sci. 2019, 9(2), 34; https://doi.org/10.3390/brainsci9020034 - 6 Feb 2019

Cited by 111 | Viewed by 12064

Abstract

Quantifying gait and postural control adds valuable information that aids in understanding neurological conditions where motor symptoms predominate and cause considerable functional impairment. Disease-specific clinical scales exist; however, they are often susceptible to subjectivity, and can lack sensitivity when identifying subtle gait and [...] Read more.

Quantifying gait and postural control adds valuable information that aids in understanding neurological conditions where motor symptoms predominate and cause considerable functional impairment. Disease-specific clinical scales exist; however, they are often susceptible to subjectivity, and can lack sensitivity when identifying subtle gait and postural impairments in prodromal cohorts and longitudinally to document disease progression. Numerous devices are available to objectively quantify a range of measurement outcomes pertaining to gait and postural control; however, efforts are required to standardise and harmonise approaches that are specific to the neurological condition and clinical assessment. Tools are urgently needed that address a number of unmet needs in neurological practice. Namely, these include timely and accurate diagnosis; disease stratification; risk prediction; tracking disease progression; and decision making for intervention optimisation and maximising therapeutic response (such as medication selection, disease staging, and targeted support). Using some recent examples of research across a range of relevant neurological conditions—including Parkinson’s disease, ataxia, and dementia—we will illustrate evidence that supports progress against these unmet clinical needs. We summarise the novel ‘big data’ approaches that utilise data mining and machine learning techniques to improve disease classification and risk prediction, and conclude with recommendations for future direction. Full article

(This article belongs to the Special Issue Diagnosis of Neurogenetic Disorders: Contribution of Next Generation Sequencing and Deep Phenotyping)

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18 pages, 967 KiB

Open AccessArticle

Impaired Recognition of Metrical and Syntactic Boundaries in Children with Developmental Language Disorders

by Susan Richards and Usha Goswami

Brain Sci. 2019, 9(2), 33; https://doi.org/10.3390/brainsci9020033 - 5 Feb 2019

Cited by 20 | Viewed by 5249

Abstract

In oral language, syntactic structure is cued in part by phrasal metrical hierarchies of acoustic stress patterns. For example, many children’s texts use prosodic phrasing comprising tightly integrated hierarchies of metre and syntax to highlight the phonological and syntactic structure of language. Children [...] Read more.

In oral language, syntactic structure is cued in part by phrasal metrical hierarchies of acoustic stress patterns. For example, many children’s texts use prosodic phrasing comprising tightly integrated hierarchies of metre and syntax to highlight the phonological and syntactic structure of language. Children with developmental language disorders (DLDs) are relatively insensitive to acoustic stress. Here, we disrupted the coincidence of metrical and syntactic boundaries as cued by stress patterns in children’s texts so that metrical and/or syntactic phrasing conflicted. We tested three groups of children: children with DLD, age-matched typically developing controls (AMC) and younger language-matched controls (YLC). Children with DLDs and younger, language-matched controls were poor at spotting both metrical and syntactic disruptions. The data are interpreted within a prosodic phrasing hypothesis of DLD based on impaired acoustic processing of speech rhythm. Full article

(This article belongs to the Special Issue Advances in the Neurocognition of Music and Language)

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15 pages, 636 KiB

Open AccessReview

The Application of Adeno-Associated Viral Vector Gene Therapy to the Treatment of Fragile X Syndrome

by David R. Hampson, Alexander W. M. Hooper and Yosuke Niibori

Brain Sci. 2019, 9(2), 32; https://doi.org/10.3390/brainsci9020032 - 2 Feb 2019

Cited by 25 | Viewed by 7371

Abstract

Viral vector-mediated gene therapy has grown by leaps and bounds over the past several years. Although the reasons for this progress are varied, a deeper understanding of the basic biology of the viruses, the identification of new and improved versions of viral vectors, [...] Read more.

Viral vector-mediated gene therapy has grown by leaps and bounds over the past several years. Although the reasons for this progress are varied, a deeper understanding of the basic biology of the viruses, the identification of new and improved versions of viral vectors, and simply the vast experience gained by extensive testing in both animal models of disease and in clinical trials, have been key factors. Several studies have investigated the efficacy of adeno-associated viral (AAV) vectors in the mouse model of fragile X syndrome where AAVs have been used to express fragile X mental retardation protein (FMRP), which is missing or highly reduced in the disorder. These studies have demonstrated a range of efficacies in different tests from full correction, to partial rescue, to no effect. Here we provide a backdrop of recent advances in AAV gene therapy as applied to central nervous system disorders, outline the salient features of the fragile X studies, and discuss several key issues for moving forward. Collectively, the findings to date from the mouse studies on fragile X syndrome, and data from clinical trials testing AAVs in other neurological conditions, indicate that AAV-mediated gene therapy could be a viable strategy for treating fragile X syndrome. Full article

(This article belongs to the Special Issue Towards Mechanism-based Treatments for Fragile X Syndrome)

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3 pages, 165 KiB

Open AccessCase Report

Missed Diagnosis of Major Depressive Disorder with Catatonia Features

by Harry Jhawer, Meesha Sidhu and Rikinkumar S. Patel

Brain Sci. 2019, 9(2), 31; https://doi.org/10.3390/brainsci9020031 - 2 Feb 2019

Cited by 10 | Viewed by 5551

Abstract

Catatonia is often a presentation of extreme anxiety and depression. Missing the diagnosis of catatonia would lead to improper treatment, which could be life-threatening. A thorough physical and psychiatric assessment is required for detecting the catatonic symptoms, especially, mutism and negativism in patients [...] Read more.

Catatonia is often a presentation of extreme anxiety and depression. Missing the diagnosis of catatonia would lead to improper treatment, which could be life-threatening. A thorough physical and psychiatric assessment is required for detecting the catatonic symptoms, especially, mutism and negativism in patients with depression. We discuss the case of a 58-year-old female that was incorrectly diagnosed and treated for major depressive disorder (MDD). The patient was then correctly diagnosed with MDD with catatonic features and improved once benzodiazepine (BZD) was started. The preferred BZD was lorazepam, with a success rate of complete remission of up to 80% in adults. Treatment was started with lorazepam 1–2 mg and improvement was seen within the first ten minutes. We believed the addition of BZD in a psychotropic regimen could improve both catatonia and depression, and should be continued for 3–6 months to prevent relapses and recurrences. Full article

(This article belongs to the Special Issue Collection on Clinical Neuroscience)

15 pages, 544 KiB

Open AccessReview

Parkinsonisms and Glucocerebrosidase Deficiency: A Comprehensive Review for Molecular and Cellular Mechanism of Glucocerebrosidase Deficiency

by Emilia M. Gatto, Gustavo Da Prat, Jose Luis Etcheverry, Guillermo Drelichman and Martin Cesarini

Brain Sci. 2019, 9(2), 30; https://doi.org/10.3390/brainsci9020030 - 1 Feb 2019

Cited by 15 | Viewed by 7810

Abstract

In the last years, lysosomal storage diseases appear as a bridge of knowledge between rare genetic inborn metabolic disorders and neurodegenerative diseases such as Parkinson’s disease (PD) or frontotemporal dementia. Epidemiological studies helped promote research in the field that continues to improve our [...] Read more.

In the last years, lysosomal storage diseases appear as a bridge of knowledge between rare genetic inborn metabolic disorders and neurodegenerative diseases such as Parkinson’s disease (PD) or frontotemporal dementia. Epidemiological studies helped promote research in the field that continues to improve our understanding of the link between mutations in the glucocerebrosidase (GBA) gene and PD. We conducted a review of this link, highlighting the association in GBA mutation carriers and in Gaucher disease type 1 patients (GD type 1). A comprehensive review of the literature from January 2008 to December 2018 was undertaken. Relevance findings include: (1) There is a bidirectional interaction between GBA and α- synuclein in protein homeostasis regulatory pathways involving the clearance of aggregated proteins. (2) The link between GBA deficiency and PD appears not to be restricted to α–synuclein aggregates but also involves Parkin and PINK1 mutations. (3) Other factors help explain this association, including early and later endosomes and the lysosomal-associated membrane protein 2A (LAMP-2A) involved in the chaperone-mediated autophagy (CMA). (4) The best knowledge allows researchers to explore new therapeutic pathways alongside substrate reduction or enzyme replacement therapies. Full article

(This article belongs to the Special Issue Diagnosis of Neurogenetic Disorders: Contribution of Next Generation Sequencing and Deep Phenotyping)

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13 pages, 303 KiB

Open AccessArticle

Race, Depression, and Financial Distress in a Nationally Representative Sample of American Adults

by Shervin Assari

Brain Sci. 2019, 9(2), 29; https://doi.org/10.3390/brainsci9020029 - 30 Jan 2019

Cited by 36 | Viewed by 6191

Abstract

Background: Although depression and financial distress are correlated, this association may differ for demographic groups, particularly based on race. Aim: Using a national sample of American adults, this study tested whether the association between Major Depressive Episode (MDE) and financial distress differs between [...] Read more.

Background: Although depression and financial distress are correlated, this association may differ for demographic groups, particularly based on race. Aim: Using a national sample of American adults, this study tested whether the association between Major Depressive Episode (MDE) and financial distress differs between African Americans and Whites. Methods: The National Survey of American Life (NSAL), 2003, enrolled 3570 African American and 891 Non-Hispanic White American adults. Demographic data (age and gender), socioeconomic position (SEP; i.e., education, employment, marital status, and income), financial distress, and 12-month MDE were measured. Logistic regression was used for data analysis. Results: In the pooled sample, 12-month MDE was associated with higher odds of financial distress, above and beyond objective SEP measures. We found MDE by race interaction on financial distress, suggesting stronger association between MDE and financial distress among African Americans, compared to Whites. Conclusions: The link between MDE and financial distress depends on race. The financial needs of African Americans with depression should be addressed. Depression screening is also needed for African Americans with financial distress. Full article

12 pages, 622 KiB

Open AccessArticle

On the Relationship between P3 Latency and Mental Ability as a Function of Increasing Demands in a Selective Attention Task

by Tugba Kapanci, Sarah Merks, Thomas H. Rammsayer and Stefan J. Troche

Brain Sci. 2019, 9(2), 28; https://doi.org/10.3390/brainsci9020028 - 29 Jan 2019

Cited by 14 | Viewed by 4687

Abstract

The mental speed approach to individual differences in mental ability (MA) is based on the assumption of higher speed of information processing in individuals with higher than those with lower MA. Empirical support of this assumption has been inconsistent when speed was measured [...] Read more.

The mental speed approach to individual differences in mental ability (MA) is based on the assumption of higher speed of information processing in individuals with higher than those with lower MA. Empirical support of this assumption has been inconsistent when speed was measured by means of the P3 latency in the event-related potential (ERP). The present study investigated the association between MA and P3 latency as a function of task demands on selective attention. For this purpose, 20 men and 90 women performed on a standard continuous performance test (CPT1 condition) as well as on two further task conditions with lower (CPT0) and higher demands (CPT2) on selective attention. MA and P3 latency negatively correlated in the standard CPT, and this negative relationship even increased systematically from the CPT1 to the CPT2 condition but was absent in the CPT0 condition. The present results indicate that task demands on selective attention are decisive to observe the expected shorter P3 latency in individuals with higher compared to those with lower MA. Full article

(This article belongs to the Special Issue ERP and EEG Markers of Brain Visual Attentional Processing)

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12 pages, 742 KiB

Open AccessArticle

A Pilot Quantitative Evaluation of Early Life Language Development in Fragile X Syndrome

by Debra L. Reisinger, Rebecca C. Shaffer, Ernest V. Pedapati, Kelli C. Dominick and Craig A. Erickson

Brain Sci. 2019, 9(2), 27; https://doi.org/10.3390/brainsci9020027 - 29 Jan 2019

Cited by 13 | Viewed by 4616

Abstract

Language delay and communication deficits are a core characteristic of the fragile X syndrome (FXS) phenotype. To date, the literature examining early language development in FXS is limited potentially due to barriers in language assessment in very young children. The present study is [...] Read more.

Language delay and communication deficits are a core characteristic of the fragile X syndrome (FXS) phenotype. To date, the literature examining early language development in FXS is limited potentially due to barriers in language assessment in very young children. The present study is one of the first to examine early language development through vocal production and the language learning environment in infants and toddlers with FXS utilizing an automated vocal analysis system. Child vocalizations, conversational turns, and adult word counts in the home environment were collected and analyzed in a group of nine infants and toddlers with FXS and compared to a typically developing (TD) normative sample. Results suggest infants and toddlers with FXS are exhibiting deficits in their early language skills when compared to their chronological expectations. Despite this, when accounting for overall developmental level, their early language skills appear to be on track. Additionally, FXS caregivers utilize less vocalizations around infants and toddlers with FXS; however, additional research is needed to understand the true gap between FXS caregivers and TD caregivers. These findings provide preliminary information about the early language learning environment and support for the feasibility of utilizing an automated vocal analysis system within the FXS population that could ease data collection and further our understanding of the emergence of language development. Full article

(This article belongs to the Special Issue Towards Mechanism-based Treatments for Fragile X Syndrome)

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8 pages, 351 KiB

Open AccessReview

Potential Application of Optogenetic Stimulation in the Treatment of Pain and Migraine Headache: A Perspective from Animal Studies

by Sufang Liu, Yuanyuan Tang, Ying Xing, Phillip Kramer, Larry Bellinger and Feng Tao

Brain Sci. 2019, 9(2), 26; https://doi.org/10.3390/brainsci9020026 - 29 Jan 2019

Cited by 12 | Viewed by 5848

Abstract

Optogenetic manipulation is uniquely useful in unraveling the functional organization of neuronal circuits in the central nervous system by enabling reversible gain- or loss-of-function of discrete populations of neurons within restricted brain regions. This state-of-the-art technology can produce circuit-specific neuromodulation by overexpressing light-sensitive [...] Read more.

Optogenetic manipulation is uniquely useful in unraveling the functional organization of neuronal circuits in the central nervous system by enabling reversible gain- or loss-of-function of discrete populations of neurons within restricted brain regions. This state-of-the-art technology can produce circuit-specific neuromodulation by overexpressing light-sensitive proteins (opsins) in particular cell types of interest. Here, we discuss the principle of optogenetic manipulation and its application in pain research using animal models, and we also discuss how to potentially use optogenetic stimulation in the treatment of migraine headache in the future. Full article

(This article belongs to the Special Issue Mechanisms Underlying Alleviation of Pain)

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21 pages, 3799 KiB

Open AccessArticle

Electrical Brain Responses Reveal Sequential Constraints on Planning during Music Performance

by Brian Mathias, William J. Gehring and Caroline Palmer

Brain Sci. 2019, 9(2), 25; https://doi.org/10.3390/brainsci9020025 - 28 Jan 2019

Cited by 9 | Viewed by 4670

Abstract

Elements in speech and music unfold sequentially over time. To produce sentences and melodies quickly and accurately, individuals must plan upcoming sequence events, as well as monitor outcomes via auditory feedback. We investigated the neural correlates of sequential planning and monitoring processes by [...] Read more.

Elements in speech and music unfold sequentially over time. To produce sentences and melodies quickly and accurately, individuals must plan upcoming sequence events, as well as monitor outcomes via auditory feedback. We investigated the neural correlates of sequential planning and monitoring processes by manipulating auditory feedback during music performance. Pianists performed isochronous melodies from memory at an initially cued rate while their electroencephalogram was recorded. Pitch feedback was occasionally altered to match either an immediately upcoming Near-Future pitch (next sequence event) or a more distant Far-Future pitch (two events ahead of the current event). Near-Future, but not Far-Future altered feedback perturbed the timing of pianists’ performances, suggesting greater interference of Near-Future sequential events with current planning processes. Near-Future feedback triggered a greater reduction in auditory sensory suppression (enhanced response) than Far-Future feedback, reflected in the P2 component elicited by the pitch event following the unexpected pitch change. Greater timing perturbations were associated with enhanced cortical sensory processing of the pitch event following the Near-Future altered feedback. Both types of feedback alterations elicited feedback-related negativity (FRN) and P3a potentials and amplified spectral power in the theta frequency range. These findings suggest similar constraints on producers’ sequential planning to those reported in speech production. Full article

(This article belongs to the Special Issue Advances in the Neurocognition of Music and Language)

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20 pages, 2614 KiB

Open AccessArticle

Connectivity Analysis Using Functional Brain Networks to Evaluate Cognitive Activity during 3D Modelling

by Muhammad Zeeshan Baig and Manolya Kavakli

Brain Sci. 2019, 9(2), 24; https://doi.org/10.3390/brainsci9020024 - 24 Jan 2019

Cited by 10 | Viewed by 4476

Abstract

Modelling 3D objects in CAD software requires special skills which require a novice user to undergo a series of training exercises to obtain. To minimize the training time for a novice user, the user-dependent factors must be studied. we have presented a comparative [...] Read more.

Modelling 3D objects in CAD software requires special skills which require a novice user to undergo a series of training exercises to obtain. To minimize the training time for a novice user, the user-dependent factors must be studied. we have presented a comparative analysis of novice/expert information flow patterns. We have used Normalized Transfer Entropy (NTE) and Electroencephalogram (EEG) to investigate the differences. The experiment was divided into three cognitive states i.e., rest, drawing, and manipulation. We applied classification algorithms on NTE matrices and graph theory measures to see the effectiveness of NTE. The results revealed that the experts show approximately the same cognitive activation in drawing and manipulation states, whereas for novices the brain activation is more in manipulation state than drawing state. The hemisphere- and lobe-wise analysis showed that expert users have developed an ability to control the information flow in various brain regions. On the other hand, novice users have shown a continuous increase in information flow activity in almost all regions when doing drawing and manipulation tasks. A classification accuracy of more than 90% was achieved with a simple K-nearest neighbors (k-NN) to classify novice and expert users. The results showed that the proposed technique can be used to develop adaptive 3D modelling systems. Full article

(This article belongs to the Special Issue Collection on Cognitive Neuroscience)

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20 pages, 270 KiB

Open AccessArticle

Neurostimulation for Intractable Chronic Pain

by Timothy R. Deer, Sameer Jain, Corey Hunter and Krishnan Chakravarthy

Brain Sci. 2019, 9(2), 23; https://doi.org/10.3390/brainsci9020023 - 24 Jan 2019

Cited by 58 | Viewed by 10554

Abstract

The field of neuromodulation has seen unprecedented growth over the course of the last decade with novel waveforms, hardware advancements, and novel chronic pain indications. We present here an updated review on spinal cord stimulation, dorsal root ganglion stimulation, and peripheral nerve stimulation. [...] Read more.

The field of neuromodulation has seen unprecedented growth over the course of the last decade with novel waveforms, hardware advancements, and novel chronic pain indications. We present here an updated review on spinal cord stimulation, dorsal root ganglion stimulation, and peripheral nerve stimulation. We focus on mechanisms of action, clinical indications, and future areas of research. We also present current drawbacks with current stimulation technology and suggest areas of future advancements. Given the current shortage of viable treatment options using a pharmacological based approach and conservative interventional therapies, neuromodulation presents an interesting area of growth and development for the interventional pain field and provides current and future practitioners a fresh outlook with regards to its place in the chronic pain treatment paradigm. Full article

(This article belongs to the Special Issue Neuromodulation for Intractable Pain)

3 pages, 155 KiB

Open AccessEditorial

Brain–Computer Interfaces for Human Augmentation

by Davide Valeriani, Caterina Cinel and Riccardo Poli

Brain Sci. 2019, 9(2), 22; https://doi.org/10.3390/brainsci9020022 - 24 Jan 2019

Cited by 12 | Viewed by 6445

Abstract

The field of brain–computer interfaces (BCIs) has grown rapidly in the last few decades, allowing the development of ever faster and more reliable assistive technologies for converting brain activity into control signals for external devices for people with severe disabilities [...] Full article

(This article belongs to the Special Issue Brain-Computer Interfaces for Human Augmentation)

8 pages, 2699 KiB

Open AccessReview

Blood Pressure Gradients in the Brain: Their Importance to Understanding Pathogenesis of Cerebral Small Vessel Disease

by J. David Spence

Brain Sci. 2019, 9(2), 21; https://doi.org/10.3390/brainsci9020021 - 23 Jan 2019

Cited by 38 | Viewed by 11454

Abstract

The term “lacunar infarction” referred to small infarctions in the basal ganglia, internal capsule, thalamus, and brainstem, due to hypertensive small vessel disease. However, it has become common to refer to all small infarctions as lacunar. It is important to understand that true [...] Read more.

The term “lacunar infarction” referred to small infarctions in the basal ganglia, internal capsule, thalamus, and brainstem, due to hypertensive small vessel disease. However, it has become common to refer to all small infarctions as lacunar. It is important to understand that true lacunes occur in a phylogenetically ancient part of the brain, the “vascular centrencephalon”, where short straight arteries with few branches transmit high blood pressure straight through to end-arterioles. The cortex is supplied by long arteries with many branches, so there is a very large blood pressure gradient in the brain. When blood pressure in the brachial artery is 117/75 mmHg, the pressure in the lenticulostriate artery would be 113/73, and the pressure in small parietal arterioles would be only 59/38 mmHg. Recent studies have reported that patients with a pulse pressure >60 mmHg and diastolic pressure <60 mmHg have a doubling of coronary risk and a 5.85-fold increase in stroke risk. This means that new low systolic targets being proposed will probably decrease the incidence of true lacunes, but increase small subcortical infarctions in the hemispheres. The pathogenesis of small vessel disease should be interpreted in the light of these blood pressure gradients. Full article

(This article belongs to the Special Issue Vascular Cognitive Impairment and Dementia Focused on Subcortical Small Vessel Disease)

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13 pages, 1069 KiB

Open AccessArticle

Victims of War: Dehydroepiandrosterone Concentrations in Hair and Their Associations with Trauma Sequelae in Palestinian Adolescents Living in the West Bank

by Lena Schindler, Mohammed Shaheen, Rotem Saar-Ashkenazy, Kifah Bani Odeh, Sophia-Helen Sass, Alon Friedman and Clemens Kirschbaum

Brain Sci. 2019, 9(2), 20; https://doi.org/10.3390/brainsci9020020 - 23 Jan 2019

Cited by 13 | Viewed by 5093

Abstract

Due to its anti-glucocorticoid properties, the steroid hormone dehydroepiandrosterone (DHEA) might play a role for coping with traumatic stress and posttraumatic stress disorder (PTSD). The majority of studies report elevated DHEA secretion and decreased cortisol/DHEA ratio associated with traumatic stress, however, contrasting results [...] Read more.

Due to its anti-glucocorticoid properties, the steroid hormone dehydroepiandrosterone (DHEA) might play a role for coping with traumatic stress and posttraumatic stress disorder (PTSD). The majority of studies report elevated DHEA secretion and decreased cortisol/DHEA ratio associated with traumatic stress, however, contrasting results have also been published. One reason for this heterogeneity might be that in past studies, DHEA has been measured in plasma or saliva samples reflecting acute hormone levels. In comparison, the current study assessed the hair levels of DHEA and cortisol as long-term markers along with self-reported data on psychopathology and coping in 92 female adolescents aged 11–16 from the West Bank affected by the Israeli–Palestinian conflict. Results showed that trauma-exposed individuals had significantly higher DHEA levels (p = 0.013) and lower cortisol/DHEA ratios (p = 0.036) than participants from the non-trauma group. Furthermore, DHEA and cortisol/DHEA ratio emerged as associated with trauma load and timing, but not with coping. By applying the novel method of DHEA analysis from hair samples, this study adds to the growing literature on the interplay of DHEA, cortisol, traumatic stress and coping, and provides valuable starting points for further research. Full article

(This article belongs to the Special Issue Neurobiological Trajectories of Psychological Trauma—Implications for Posttraumatic Stress Disorder (PTSD))

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7 pages, 1005 KiB

Open AccessBrief Report

Astrocytic Response to Acutely- and Chronically-Implanted Microelectrode Arrays in the Marmoset (Callithrix jacchus) Brain

by Samuel A. Budoff, Kim M. Yano, Fernanda C. de Mesquita, Jhulimar G. Doerl, Maxwell B. de Santana, Manuela S. L. Nascimento, Ana Carolina B. Kunicki and Mariana F. P. de Araújo

Brain Sci. 2019, 9(2), 19; https://doi.org/10.3390/brainsci9020019 - 23 Jan 2019

Cited by 8 | Viewed by 3901

Abstract

Microelectrode implants are an important tool in neuroscience research and in developing brain–machine interfaces. Data from rodents have consistently shown that astrocytes are recruited to the area surrounding implants, forming a glial scar that increases electrode impedance and reduces chronic utility. However, studies [...] Read more.

Microelectrode implants are an important tool in neuroscience research and in developing brain–machine interfaces. Data from rodents have consistently shown that astrocytes are recruited to the area surrounding implants, forming a glial scar that increases electrode impedance and reduces chronic utility. However, studies in non-human primates are scarce, with none to date in marmosets. We used glial fibrillary acidic protein (GFAP) immunostaining to characterize the acute and chronic response of the marmoset brain to microelectrodes. By using densitometry, we showed that marmoset astrocytes surround brain implants and that a glial scar is formed over time, with significant increase in the chronic condition relative to the acute condition animal. Full article

(This article belongs to the Section Neuroglia)

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13 pages, 1550 KiB

Open AccessArticle

Voice of People with Fragile X Syndrome and Their Families: Reports from a Survey on Treatment Priorities

by Jayne Dixon Weber, Elizabeth Smith, Elizabeth Berry-Kravis, Diego Cadavid, David Hessl and Craig Erickson

Brain Sci. 2019, 9(2), 18; https://doi.org/10.3390/brainsci9020018 - 23 Jan 2019

Cited by 31 | Viewed by 7492

Abstract

To date, there has been limited research on the primary concerns and treatment priorities for individuals with fragile X syndrome (FXS) and their families. The National Fragile X Foundation in collaboration with clinical investigators from industry and academia constructed a survey to investigate [...] Read more.

To date, there has been limited research on the primary concerns and treatment priorities for individuals with fragile X syndrome (FXS) and their families. The National Fragile X Foundation in collaboration with clinical investigators from industry and academia constructed a survey to investigate the main symptoms, daily living challenges, family impact, and treatment priorities for individuals with FXS and their families, which was then distributed to a large mailing list. The survey included both structured questions focused on ranking difficulties as well as qualitative analysis of open-ended questions. It was completed by 467 participants, including 439 family members or caretakers (family members/caretakers) of someone with FXS, 20 professionals who work with a person with FXS, and 8 individuals with FXS. Respondents indicated three main general areas of concern: Anxiety, behavioral problems, and learning difficulties. Important differences were noted, based on the sex and age of the individual with FXS. The results highlight the top priorities for treatment development for family members/caretakers, as well as a small group of professionals, and an even smaller group of individuals with FXS, while demonstrating challenges with “voice of the patient” research in FXS. Full article

(This article belongs to the Special Issue Towards Mechanism-based Treatments for Fragile X Syndrome)

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Brain Sci., Volume 9, Issue 2 (February 2019) – 29 articles

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