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Brain Sci., Volume 9, Issue 7 (July 2019)

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Cover Story (view full-size image) Immune dysfunction is often reported in autism spectrum disorders (ASD), however, the extent and [...] Read more.
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Open AccessArticle
Common and Distinct Functional Brain Networks for Intuitive and Deliberate Decision Making
Brain Sci. 2019, 9(7), 174; https://doi.org/10.3390/brainsci9070174
Received: 5 June 2019 / Revised: 11 July 2019 / Accepted: 19 July 2019 / Published: 20 July 2019
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Abstract
Reinforcement learning studies in rodents and primates demonstrate that goal-directed and habitual choice behaviors are mediated through different fronto-striatal systems, but the evidence is less clear in humans. In this study, functional magnetic resonance imaging (fMRI) data were collected whilst participants (n [...] Read more.
Reinforcement learning studies in rodents and primates demonstrate that goal-directed and habitual choice behaviors are mediated through different fronto-striatal systems, but the evidence is less clear in humans. In this study, functional magnetic resonance imaging (fMRI) data were collected whilst participants (n = 20) performed a conditional associative learning task in which blocks of novel conditional stimuli (CS) required a deliberate choice, and blocks of familiar CS required an intuitive choice. Using standard subtraction analysis for fMRI event-related designs, activation shifted from the dorso-fronto-parietal network, which involves dorsolateral prefrontal cortex (DLPFC) for deliberate choice of novel CS, to ventro-medial frontal (VMPFC) and anterior cingulate cortex for intuitive choice of familiar CS. Supporting this finding, psycho-physiological interaction (PPI) analysis, using the peak active areas within the PFC for novel and familiar CS as seed regions, showed functional coupling between caudate and DLPFC when processing novel CS and VMPFC when processing familiar CS. These findings demonstrate separable systems for deliberate and intuitive processing, which is in keeping with rodent and primate reinforcement learning studies, although in humans they operate in a dynamic, possibly synergistic, manner particularly at the level of the striatum. Full article
(This article belongs to the Section Neuroimaging)
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Open AccessPerspective
Neural Circuit and Clinical Insights from Intraoperative Recordings During Deep Brain Stimulation Surgery
Brain Sci. 2019, 9(7), 173; https://doi.org/10.3390/brainsci9070173
Received: 28 June 2019 / Revised: 17 July 2019 / Accepted: 18 July 2019 / Published: 20 July 2019
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Abstract
Observations using invasive neural recordings from patient populations undergoing neurosurgical interventions have led to critical breakthroughs in our understanding of human neural circuit function and malfunction. The opportunity to interact with patients during neurophysiological mapping allowed for early insights in functional localization to [...] Read more.
Observations using invasive neural recordings from patient populations undergoing neurosurgical interventions have led to critical breakthroughs in our understanding of human neural circuit function and malfunction. The opportunity to interact with patients during neurophysiological mapping allowed for early insights in functional localization to improve surgical outcomes, but has since expanded into exploring fundamental aspects of human cognition including reward processing, language, the storage and retrieval of memory, decision-making, as well as sensory and motor processing. The increasing use of chronic neuromodulation, via deep brain stimulation, for a spectrum of neurological and psychiatric conditions has in tandem led to increased opportunity for linking theories of cognitive processing and neural circuit function. Our purpose here is to motivate the neuroscience and neurosurgical community to capitalize on the opportunities that this next decade will bring. To this end, we will highlight recent studies that have successfully leveraged invasive recordings during deep brain stimulation surgery to advance our understanding of human cognition with an emphasis on reward processing, improving clinical outcomes, and informing advances in neuromodulatory interventions. Full article
Open AccessArticle
Upregulation of IL-1 Receptor Antagonist in a Mouse Model of Migraine
Brain Sci. 2019, 9(7), 172; https://doi.org/10.3390/brainsci9070172
Received: 9 July 2019 / Accepted: 18 July 2019 / Published: 19 July 2019
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Abstract
Migraine is a disorder characterized by attacks of monolateral headaches, often accompanied by nausea, vomiting, and photophobia. Around 30% of patients also report aura symptoms. The cause of the aura is believed to be related to the cortical spreading depression (CSD), a wave [...] Read more.
Migraine is a disorder characterized by attacks of monolateral headaches, often accompanied by nausea, vomiting, and photophobia. Around 30% of patients also report aura symptoms. The cause of the aura is believed to be related to the cortical spreading depression (CSD), a wave of neuronal and glial depolarization originating in the occipital cortex, followed by temporary neuronal silencing. During a migraine attack, increased expression of inflammatory mediators, along with a decrease in the expression of anti-inflammatory genes, have been observed. The aim of this study was to evaluate the expression of inflammatory genes, in particular that of IL-1 receptor antagonist (IL-1RN), following CSD in a mouse model of familial hemiplegic migraine type 1 (FHM-1). We show here that the expression of IL-1RN was upregulated after the CSD, suggesting a possible attempt to modulate the inflammatory response. This study allows researchers to better understand the development of the disease and aids in the search for new therapeutic strategies in migraine. Full article
(This article belongs to the Special Issue Neuromodulation for Intractable Pain)
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Open AccessArticle
Corticotropin Releasing Factor Type 1 and 2 Receptor Signaling in the Medial Prefrontal Cortex Modulates Binge-Like Ethanol Consumption in C57BL/6J Mice
Brain Sci. 2019, 9(7), 171; https://doi.org/10.3390/brainsci9070171
Received: 10 June 2019 / Revised: 15 July 2019 / Accepted: 17 July 2019 / Published: 19 July 2019
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Abstract
Corticotropin releasing factor (CRF) signaling via limbic CRF1 and 2 receptors (CRF1R and CRF2R, respectively) is known to modulate binge-like ethanol consumption in rodents. Though CRF signaling in the medial prefrontal cortex (mPFC) has been shown to modulate anxiety-like behavior and ethanol seeking, [...] Read more.
Corticotropin releasing factor (CRF) signaling via limbic CRF1 and 2 receptors (CRF1R and CRF2R, respectively) is known to modulate binge-like ethanol consumption in rodents. Though CRF signaling in the medial prefrontal cortex (mPFC) has been shown to modulate anxiety-like behavior and ethanol seeking, its role in binge ethanol intake is unknown. Here, we used “drinking-in-the-dark” (DID) procedures in male and female C57BL/6J mice to address this gap in the literature. First, the role of CRF1R and CRF2R signaling in the mPFC on ethanol consumption was evaluated through site-directed pharmacology. Next, we evaluated if CRF1R antagonist reduction of binge-intake was modulated in part through CRF2R activation by co-administration of a CRF1R and CRF2R antagonist. Intra-mPFC inhibition of CRF1R and activation of CRF2R resulted in decreased binge-like ethanol intake. Further, the inhibitory effect of the CRF1R antagonist was attenuated by co-administration of a CRF2R antagonist. We provide novel evidence that (1) inhibition of CRF1R or activation of CRF2R in the mPFC reduces binge-like ethanol intake; and (2) the effect of CRF1R antagonism may be mediated via enhanced CRF2R activation. These observations provide the first direct behavioral pharmacological evidence that CRF receptor activity in the mPFC modulates binge-like ethanol consumption. Full article
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Open AccessArticle
White Matter Hyperintensity Regression: Comparison of Brain Atrophy and Cognitive Profiles with Progression and Stable Groups
Brain Sci. 2019, 9(7), 170; https://doi.org/10.3390/brainsci9070170
Received: 28 May 2019 / Revised: 7 July 2019 / Accepted: 16 July 2019 / Published: 19 July 2019
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Abstract
Subcortical white matter hyperintensities (WMHs) in the aging population frequently represent vascular injury that may lead to cognitive impairment. WMH progression is well described, but the factors underlying WMH regression remain poorly understood. A sample of 351 participants from the Alzheimer’s Disease Neuroimaging [...] Read more.
Subcortical white matter hyperintensities (WMHs) in the aging population frequently represent vascular injury that may lead to cognitive impairment. WMH progression is well described, but the factors underlying WMH regression remain poorly understood. A sample of 351 participants from the Alzheimer’s Disease Neuroimaging Initiative 2 (ADNI2) was explored who had WMH volumetric quantification, structural brain measures, and cognitive measures (memory and executive function) at baseline and after approximately 2 years. Selected participants were categorized into three groups based on WMH change over time, including those that demonstrated regression (n = 96; 25.5%), stability (n = 72; 19.1%), and progression (n = 209; 55.4%). There were no significant differences in age, education, sex, or cognitive status between groups. Analysis of variance demonstrated significant differences in atrophy between the progression and both regression (p = 0.004) and stable groups (p = 0.012). Memory assessments improved over time in the regression and stable groups but declined in the progression group (p = 0.003; p = 0.018). WMH regression is associated with decreased brain atrophy and improvement in memory performance over two years compared to those with WMH progression, in whom memory and brain atrophy worsened. These data suggest that WMHs are dynamic and associated with changes in atrophy and cognition. Full article
(This article belongs to the collection Collection on Cognitive Neuroscience)
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Open AccessArticle
Domain-Specific Expectations in Music Segmentation
Brain Sci. 2019, 9(7), 169; https://doi.org/10.3390/brainsci9070169
Received: 20 June 2019 / Revised: 12 July 2019 / Accepted: 16 July 2019 / Published: 17 July 2019
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Abstract
The acoustic cues that guide the assignment of phrase boundaries in music (pauses and pitch movements) overlap with those that are known for speech prosody. Based on this, researchers have focused on highlighting the similarities and neural resources shared between music and speech [...] Read more.
The acoustic cues that guide the assignment of phrase boundaries in music (pauses and pitch movements) overlap with those that are known for speech prosody. Based on this, researchers have focused on highlighting the similarities and neural resources shared between music and speech prosody segmentation. The possibility that music-specific expectations add to acoustic cues in driving the segmentation of music into phrases could weaken this bottom-up view, but it remains underexplored. We tested for domain-specific expectations in music segmentation by comparing the segmentation of the same set of ambiguous stimuli under two different instructions: stimuli were either presented as speech prosody or as music. We measured how segmentation differed, in each instruction group, from a common reference (natural speech); thus, focusing on how instruction affected delexicalization effects (natural speech vs. transformed versions with no phonetic content) on segmentation. We saw interactions between delexicalization and instruction on most segmentation indices, suggesting that there is a music mode, different from a speech prosody mode in segmentation. Our findings highlight the importance of top-down influences in segmentation, and they contribute to rethinking the analogy between music and speech prosody. Full article
(This article belongs to the Special Issue Advances in the Neurocognition of Music and Language)
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Open AccessPerspective
An Overview of Experimental and Clinical Spinal Cord Findings in Alzheimer’s Disease
Brain Sci. 2019, 9(7), 168; https://doi.org/10.3390/brainsci9070168
Received: 16 May 2019 / Revised: 10 July 2019 / Accepted: 16 July 2019 / Published: 17 July 2019
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Abstract
Alzheimer’s disease (AD) is a neurodegenerative disorder that occurs mainly in the elderly and presenile life stages. It is estimated that by the year 2050, 135 million people will be affected by AD worldwide, representing a huge burden to society. The pathological hallmarks [...] Read more.
Alzheimer’s disease (AD) is a neurodegenerative disorder that occurs mainly in the elderly and presenile life stages. It is estimated that by the year 2050, 135 million people will be affected by AD worldwide, representing a huge burden to society. The pathological hallmarks of AD mainly include intracellular neurofibrillary tangles (NFTs) caused by hyperphosphorylation of tau protein, formation of extracellular amyloid plaques, and massive neural cell death in the affected nervous system. The pathogenesis of AD is very complicated, and recent scientific research on AD is mainly concentrated on the cortex and hippocampus. Although the spinal cord is a pivotal part of the central nervous system, there are a limited number of studies focusing on the spinal cord. As an extension of the brain, the spinal cord functions as the bridge between the brain and various parts of the body. However, pathological changes in the spinal cord in AD have not been comprehensively and systematically studied at present. We here review the existing progress on the pathological features of AD in the spinal cord. Full article
(This article belongs to the Special Issue Dementia and Cognitive Ageing)
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Open AccessArticle
Sex Differences in the Effect of Alcohol Drinking on Myelinated Axons in the Anterior Cingulate Cortex of Adolescent Rats
Brain Sci. 2019, 9(7), 167; https://doi.org/10.3390/brainsci9070167
Received: 19 June 2019 / Revised: 15 July 2019 / Accepted: 15 July 2019 / Published: 16 July 2019
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Abstract
Cognitive deficits associated with teenage drinking may be due to disrupted myelination of prefrontal circuits. To better understand how alcohol affects myelination, male and female Wistar rats (n = 7–9/sex/treatment) underwent two weeks of intermittent operant self-administration of sweetened alcohol or sweetened [...] Read more.
Cognitive deficits associated with teenage drinking may be due to disrupted myelination of prefrontal circuits. To better understand how alcohol affects myelination, male and female Wistar rats (n = 7–9/sex/treatment) underwent two weeks of intermittent operant self-administration of sweetened alcohol or sweetened water early in adolescence (postnatal days 28–42) and we tested for macro- and microstructural changes to myelin. We previously reported data from the males of this study showing that alcohol drinking reduced myelinated fiber density in layers II–V of the anterior cingulate division of the medial prefrontal cortex (Cg1); herein, we show that myelinated fiber density was not significantly altered by alcohol in females. Alcohol drinking patterns were similar in both sexes, but males were in a pre-pubertal state for a larger proportion of the alcohol exposure period, which may have contributed to the differential effects on myelinated fiber density. To gain more insight into how alcohol impacts myelinated axons, brain sections from a subset of these animals (n = 6/sex/treatment) were used for microstructural analyses of the nodes of Ranvier. Confocal analysis of nodal domains, flanked by immunofluorescent-labeled contactin-associated protein (Caspr) clusters, indicated that alcohol drinking reduced nodal length-to-width ratios in layers II/III of the Cg1 in both sexes. Despite sex differences in the underlying cause (larger diameter axons after alcohol in males vs. shorter nodal lengths after alcohol in females), reduced nodal ratios could have important implications for the speed and integrity of neural transmission along these axons in both males and females. Alcohol-induced changes to myelinated axonal populations in the Cg1 may contribute to long-lasting changes in prefrontal function associated with early onset drinking. Full article
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Open AccessArticle
Marijuana Use among African American Older Adults in Economically Challenged Areas of South Los Angeles
Brain Sci. 2019, 9(7), 166; https://doi.org/10.3390/brainsci9070166
Received: 1 July 2019 / Revised: 11 July 2019 / Accepted: 15 July 2019 / Published: 16 July 2019
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Abstract
Purpose: This study explored demographic, social, behavioral, and health factors associated with current marijuana use (MU) among African American older adults who were residing in economically challenged areas of south Los Angeles. Methods: This community-based study recruited a consecutive sample of African American [...] Read more.
Purpose: This study explored demographic, social, behavioral, and health factors associated with current marijuana use (MU) among African American older adults who were residing in economically challenged areas of south Los Angeles. Methods: This community-based study recruited a consecutive sample of African American older adults (n = 340), age ≥ 55 years, residing in economically challenged areas of South Los Angeles. Interviews were conducted to collect data. Demographics (age and gender), socioeconomic status (educational attainment, income, and financial strain), marital status, living alone, health behaviors (alcohol drinking and cigarette smoking), health status (number of chronic medical conditions, body mass index, depression, and chronic pain), and current MU were collected. Logistic regression was used to analyze the data. Results: Thirty (9.1%) participants reported current MU. Age, educational attainment, chronic medical conditions, and obesity were negatively associated with current MU. Gender, income, financial strain, living alone, marital status, smoking cigarettes, drinking alcohol, depression, and pain did not correlate with MU. Conclusion: Current MU is more common in younger, healthier, less obese, less educated African American older adults. It does not seem that African American older adults use marijuana for the self-medication of chronic disease, pain, or depression. For African American older adults, MU also does not co-occur with cigarette smoking and alcohol drinking. These results may help clinicians who provide services for older African Americans in economically challenged urban areas. Full article
(This article belongs to the Special Issue Cannabis: Neuropsychiatry and Its Effects on Brain and Behavior)
Open AccessFeature PaperArticle
Systemic Dental Pulp Stem Cell Secretome Therapy in a Mouse Model of Amyotrophic Lateral Sclerosis
Brain Sci. 2019, 9(7), 165; https://doi.org/10.3390/brainsci9070165
Received: 21 June 2019 / Revised: 11 July 2019 / Accepted: 12 July 2019 / Published: 14 July 2019
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Abstract
Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron (MN) disease with no cure. Accumulating evidence indicates ALS involves a complex interaction between central glia and the peripheral immune response and neuromuscular interface. Stem cell secretomes contain various beneficial trophic factors and cytokines, [...] Read more.
Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron (MN) disease with no cure. Accumulating evidence indicates ALS involves a complex interaction between central glia and the peripheral immune response and neuromuscular interface. Stem cell secretomes contain various beneficial trophic factors and cytokines, and we recently demonstrated that administration of the secretome of adipose-derived stem cells (ASCs) during early neuromuscular junction (NMJ) denervation in the mutant superoxide dismutase (mSOD1G93A) ALS mouse ameliorated NMJ disruption. In the present study, we hypothesized that administration of dental pulp stem cell secretome in the form of conditioned medium (DPSC-CM) at different stages of disease would promote NMJ innervation, prevent MN loss and extend lifespan. Our findings show that DPSC-CM significantly improved NMJ innervation at postnatal day (PD) 47 compared to vehicle treated mSOD1G93A mice (p < 0.05). During late pre-symptomatic stages (PD70-P91), DPSC-CM significantly increased MN survival (p < 0.01) and NMJ preservation (p < 0.05), while reactive gliosis in the ventral horn remained unaffected. For DPSC-CM treated mSOD1G93A mice beginning at symptom onset, post-onset days of survival as well as overall lifespan was significantly increased compared to vehicle treated mice (p < 0.05). This is the first study to show therapeutic benefits of systemic DPSC secretome in experimental ALS, and establishes a foundation for future research into the treatment effects and mechanistic analyses of DPSC and other stem cell secretome therapies in ALS. Full article
(This article belongs to the Special Issue Novel Targets and Therapies for Motor Neuron Diseases)
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Open AccessCommentary
From Extinction Learning to Anxiety Treatment: Mind the Gap
Brain Sci. 2019, 9(7), 164; https://doi.org/10.3390/brainsci9070164
Received: 15 June 2019 / Revised: 3 July 2019 / Accepted: 9 July 2019 / Published: 11 July 2019
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Abstract
Laboratory models of extinction learning in animals and humans have the potential to illuminate methods for improving clinical treatment of fear-based clinical disorders. However, such translational research often neglects important differences between threat responses in animals and fear learning in humans, particularly as [...] Read more.
Laboratory models of extinction learning in animals and humans have the potential to illuminate methods for improving clinical treatment of fear-based clinical disorders. However, such translational research often neglects important differences between threat responses in animals and fear learning in humans, particularly as it relates to the treatment of clinical disorders. Specifically, the conscious experience of fear and anxiety, along with the capacity to deliberately engage top-down cognitive processes to modulate that experience, involves distinct brain circuitry and is measured and manipulated using different methods than typically used in laboratory research. This paper will identify how translational research that investigates methods of enhancing extinction learning can more effectively model such elements of human fear learning, and how doing so will enhance the relevance of this research to the treatment of fear-based psychological disorders. Full article
(This article belongs to the Special Issue Neurobiology of Fear: From Basic Mechanisms to Therapeutic Approaches)
Open AccessArticle
Infants’ Individuation of Faces by Gender
Brain Sci. 2019, 9(7), 163; https://doi.org/10.3390/brainsci9070163
Received: 15 May 2019 / Revised: 6 July 2019 / Accepted: 7 July 2019 / Published: 11 July 2019
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Abstract
By 3 months of age, infants can perceptually distinguish faces based upon differences in gender. However, it is still unknown when infants begin using these perceptual differences to represent faces in a conceptual, kind-based manner. The current study examined this issue by using [...] Read more.
By 3 months of age, infants can perceptually distinguish faces based upon differences in gender. However, it is still unknown when infants begin using these perceptual differences to represent faces in a conceptual, kind-based manner. The current study examined this issue by using a violation-of-expectation manual search individuation paradigm to assess 12- and 24-month-old infants’ kind-based representations of faces varying by gender. While infants of both ages successfully individuated human faces from non-face shapes in a control condition, only the 24-month-old infants’ reaching behaviors provided evidence of their individuating male from female faces. The current findings help specify when infants begin to represent male and female faces as being conceptually distinct and may serve as a starting point for socio-cognitive biases observed later in development. Full article
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Open AccessArticle
Relationship between Ischemic Stroke and Pulse Rate Variability as a Surrogate of Heart Rate Variability
Brain Sci. 2019, 9(7), 162; https://doi.org/10.3390/brainsci9070162
Received: 3 June 2019 / Revised: 27 June 2019 / Accepted: 3 July 2019 / Published: 10 July 2019
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Abstract
Autonomic reflex ascertains cardiovascular homeostasis during standing. Impaired autonomic reflex could lead to dizziness and falls while standing; this is prevalent in stroke survivors. Pulse rate variability (PRV) has been utilized in the literature in lieu of heart rate variability (HRV) for ambulatory [...] Read more.
Autonomic reflex ascertains cardiovascular homeostasis during standing. Impaired autonomic reflex could lead to dizziness and falls while standing; this is prevalent in stroke survivors. Pulse rate variability (PRV) has been utilized in the literature in lieu of heart rate variability (HRV) for ambulatory and portable monitoring of autonomic reflex predominantly in young, healthy individuals. Here, we compared the PRV with gold standard HRV for monitoring autonomic reflex in ischemic stroke survivors. Continuous blood pressure and electrocardiography were acquired from ischemic stroke survivors (64 ± 1 years) and age-matched controls (65 ± 2 years) during a 10-minute sit-to-stand test. Beat-by-beat heart period (represented by RR and peak-to-peak (PP) intervals), systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse arrival time (PAT), an indicator of arterial stiffness, were derived. Time and frequency domain HRV (from RR intervals) and PRV (from PP intervals) metrics were extracted. PAT was lower (248 ± 7 ms vs. 270 ± 8 ms, p < 0.05) suggesting higher arterial stiffness in stroke survivors compared to controls during standing. Further, compared to controls, the agreement between HRV and PRV was impaired in stroke survivors while standing. The study outcomes suggest that caution should be exercised when considering PRV as a surrogate of HRV for monitoring autonomic cardiovascular control while standing in stroke survivors. Full article
(This article belongs to the collection Collection on Systems Neuroscience)
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Open AccessArticle
Proactive and Reactive Language Control in the Bilingual Brain
Brain Sci. 2019, 9(7), 161; https://doi.org/10.3390/brainsci9070161
Received: 4 June 2019 / Revised: 28 June 2019 / Accepted: 8 July 2019 / Published: 10 July 2019
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Abstract
The current experiment investigated bilingual language control within the dual mechanisms framework. In an fMRI investigation of morphosyntactic rule production, the presence or absence of target language cues was manipulated to investigate the neural mechanisms associated with proactive and reactive global language control [...] Read more.
The current experiment investigated bilingual language control within the dual mechanisms framework. In an fMRI investigation of morphosyntactic rule production, the presence or absence of target language cues was manipulated to investigate the neural mechanisms associated with proactive and reactive global language control mechanisms. Patterns of activation across nine regions of interest (ROIs) were investigated in seventeen early Spanish–English bilingual speakers. A cue by phase interaction in the left dorsolateral prefrontal cortex (DLPFC) and pre-supplementary motor area (Pre-SMA) was observed, suggesting that these regions were more active during cue phases, and less active during execution phases, when target language cues were presented. Individual differences analyses showed that variability in proactive control (informative > non-informative cued trial activation during preparation) in the basal ganglia was correlated with proactive control in the left DLPFC, left inferior frontal gyrus (IFG), and right precentral ROIs. In contrast, reactive control (non-informative > informative cued activation during execution) in the anterior cingulate was correlated with reactive control in the Pre-SMA and left orbital frontal ROIs. The results suggest that, consistent with the dual mechanisms framework, bilinguals differ in the degree to which they use cues to proactively prepare to use a target language. Full article
(This article belongs to the Special Issue Cognitive Neuroscience of Cross-Language Interaction in Bilinguals)
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Open AccessPerspective
Disseminated Coccidioidomycosis to the Spine—Case Series and Review of Literature
Brain Sci. 2019, 9(7), 160; https://doi.org/10.3390/brainsci9070160
Received: 31 May 2019 / Revised: 3 July 2019 / Accepted: 5 July 2019 / Published: 7 July 2019
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Abstract
Coccidioidomycosis is a fungal infectious disease caused by the Coccidioides species endemic to Southwestern United States. Symptomatic patients typically present as community-acquired pneumonia. Uncommonly, in about 1% of infections, hematogenous extra pulmonary systemic dissemination involving skin, musculoskeletal system, and meninges occur. Disseminated spinal [...] Read more.
Coccidioidomycosis is a fungal infectious disease caused by the Coccidioides species endemic to Southwestern United States. Symptomatic patients typically present as community-acquired pneumonia. Uncommonly, in about 1% of infections, hematogenous extra pulmonary systemic dissemination involving skin, musculoskeletal system, and meninges occur. Disseminated spinal infection is treated with antifungal drugs and/or surgical treatment. A retrospective review of medical records at our institution was done between January 2009 to December 2018 and we present three cases of spinal coccidioidomycosis and review the current literature. Disseminated coccidioidomycosis can lead to spondylitis that can present as discitis or a localized spinal or paraspinal abscess. Spinal coccidioidomycosis is typically managed with antifungal treatments but can include surgical treatment in the setting poor response to medical therapy, intractable pain, presence of neurological deficits due to compression, or structural spinal instability. Full article
(This article belongs to the Special Issue Surgery for Spine Disease and Intractable Pain)
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Open AccessCase Report
Mixed Small Vessel Disease in a Patient with Dementia with Lewy Bodies
Brain Sci. 2019, 9(7), 159; https://doi.org/10.3390/brainsci9070159
Received: 24 May 2019 / Revised: 25 June 2019 / Accepted: 2 July 2019 / Published: 4 July 2019
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Abstract
Background: Cerebral amyloid angiopathy (CAA) is characterized by deposition of amyloid in small/medium size brain vessels, and may coexist with Alzheimer’s disease or dementia with Lewy bodies (DLB). We describe a patient with a clinical diagnosis of DLB and imaging/biochemical characteristics suggestive of [...] Read more.
Background: Cerebral amyloid angiopathy (CAA) is characterized by deposition of amyloid in small/medium size brain vessels, and may coexist with Alzheimer’s disease or dementia with Lewy bodies (DLB). We describe a patient with a clinical diagnosis of DLB and imaging/biochemical characteristics suggestive of mixed small vessel disease (both CAA and non-amyloid microangiopathy). Methods: Clinical evaluation according to recent diagnostic criteria, magnetic resonance imaging, dopamine-transporter scan (DAT-scan) and cerebrospinal fluid (CSF) analysis for dementia biomarkers were all performed. Results: The patient is a 71-year-old male, fulfilling criteria for probable DLB, with a positive DAT-scan, but with multiple microbleeds in a cortical-subcortical location suggestive of CAA, some microbleeds in deep brain nuclei suggestive of non-amyloid microangiopathy and abnormal levels of only amyloid-beta (Aβ42) in CSF. Conclusion: Coexistent mixed vascular and neurodegenerative disorders are frequent in older subjects with dementia and each one of the underlying pathologies may contribute to, or modify the clinical presentation. Full article
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Open AccessReview
The Impact of Ethologically Relevant Stressors on Adult Mammalian Neurogenesis
Brain Sci. 2019, 9(7), 158; https://doi.org/10.3390/brainsci9070158
Received: 11 June 2019 / Revised: 30 June 2019 / Accepted: 2 July 2019 / Published: 4 July 2019
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Abstract
Adult neurogenesis—the formation and functional integration of adult-generated neurons—remains a hot neuroscience topic. Decades of research have identified numerous endogenous (such as neurotransmitters and hormones) and exogenous (such as environmental enrichment and exercise) factors that regulate the various neurogenic stages. Stress, an exogenous [...] Read more.
Adult neurogenesis—the formation and functional integration of adult-generated neurons—remains a hot neuroscience topic. Decades of research have identified numerous endogenous (such as neurotransmitters and hormones) and exogenous (such as environmental enrichment and exercise) factors that regulate the various neurogenic stages. Stress, an exogenous factor, has received a lot of attention. Despite the large number of reviews discussing the impact of stress on adult neurogenesis, no systematic review on ethologically relevant stressors exists to date. The current review details the effects of conspecifically-induced psychosocial stress (specifically looking at the lack or disruption of social interactions and confrontation) as well as non-conspecifically-induced stress on mammalian adult neurogenesis. The underlying mechanisms, as well as the possible functional role of the altered neurogenesis level, are also discussed. The reviewed data suggest that ethologically relevant stressors reduce adult neurogenesis. Full article
(This article belongs to the Special Issue Adult Neurogenesis and Neurological Disorders)
Open AccessArticle
Poor Synchronization to Musical Beat Generalizes to Speech
Brain Sci. 2019, 9(7), 157; https://doi.org/10.3390/brainsci9070157
Received: 17 June 2019 / Accepted: 1 July 2019 / Published: 4 July 2019
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Abstract
The rhythmic nature of speech may recruit entrainment mechanisms in a manner similar to music. In the current study, we tested the hypothesis that individuals who display a severe deficit in synchronizing their taps to a musical beat (called beat-deaf here) would also [...] Read more.
The rhythmic nature of speech may recruit entrainment mechanisms in a manner similar to music. In the current study, we tested the hypothesis that individuals who display a severe deficit in synchronizing their taps to a musical beat (called beat-deaf here) would also experience difficulties entraining to speech. The beat-deaf participants and their matched controls were required to align taps with the perceived regularity in the rhythm of naturally spoken, regularly spoken, and sung sentences. The results showed that beat-deaf individuals synchronized their taps less accurately than the control group across conditions. In addition, participants from both groups exhibited more inter-tap variability to natural speech than to regularly spoken and sung sentences. The findings support the idea that acoustic periodicity is a major factor in domain-general entrainment to both music and speech. Therefore, a beat-finding deficit may affect periodic auditory rhythms in general, not just those for music. Full article
(This article belongs to the Special Issue Advances in the Neurocognition of Music and Language)
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Open AccessArticle
Neural State Monitoring in the Treatment of Epilepsy: Seizure Prediction—Conceptualization to First-In-Man Study
Brain Sci. 2019, 9(7), 156; https://doi.org/10.3390/brainsci9070156
Received: 17 January 2019 / Revised: 1 May 2019 / Accepted: 17 May 2019 / Published: 1 July 2019
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Abstract
This research study is part of a therapy development effort in which a novel approach was taken to develop an implantable electroencephalographic (EEG) based brain monitoring and seizure prediction system. Previous attempts to predict seizures by other groups had not been demonstrated to [...] Read more.
This research study is part of a therapy development effort in which a novel approach was taken to develop an implantable electroencephalographic (EEG) based brain monitoring and seizure prediction system. Previous attempts to predict seizures by other groups had not been demonstrated to be statistically more successful than chance. The primary clinical findings from this group were published in a clinical paper; however much of the fundamental technology, including the strategy and techniques behind the development of the seizure advisory system have not been published. Development of this technology comprised several steps: a vast high quality database of EEG recordings was assembled, a structured approach to algorithm development was undertaken, an implantable 16-channel subdural neural monitoring and seizure advisory system was designed and built, preclinical studies were conducted in a canine model, and a First-In-Man study involving implantation of 15 patients followed for two years was conducted to evaluate the algorithm. The algorithm was successfully trained to correctly provide a) notification of a high likelihood of seizure in 11 of 14 patients, and b) notification of a low likelihood of seizure in 5 of 14 patients (NCT01043406). Continuous neural state monitoring shows promise for applications in seizure prediction and likelihood estimation, and insights for further research and development are drawn. Full article
(This article belongs to the Special Issue Diagnosis and Surgical Treatment of Epilepsy) Printed Edition available
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Open AccessArticle
Regional Analysis of the Brain Transcriptome in Mice Bred for High and Low Methamphetamine Consumption
Brain Sci. 2019, 9(7), 155; https://doi.org/10.3390/brainsci9070155
Received: 3 June 2019 / Revised: 20 June 2019 / Accepted: 26 June 2019 / Published: 30 June 2019
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Abstract
Transcriptome profiling can broadly characterize drug effects and risk for addiction in the absence of drug exposure. Modern large-scale molecular methods, including RNA-sequencing (RNA-Seq), have been extensively applied to alcohol-related disease traits, but rarely to risk for methamphetamine (MA) addiction. We used RNA-Seq [...] Read more.
Transcriptome profiling can broadly characterize drug effects and risk for addiction in the absence of drug exposure. Modern large-scale molecular methods, including RNA-sequencing (RNA-Seq), have been extensively applied to alcohol-related disease traits, but rarely to risk for methamphetamine (MA) addiction. We used RNA-Seq data from selectively bred mice with high or low risk for voluntary MA intake to construct coexpression and cosplicing networks for differential risk. Three brain reward circuitry regions were explored, the nucleus accumbens (NAc), prefrontal cortex (PFC), and ventral midbrain (VMB). With respect to differential gene expression and wiring, the VMB was more strongly affected than either the PFC or NAc. Coexpression network connectivity was higher in the low MA drinking line than in the high MA drinking line in the VMB, oppositely affected in the NAc, and little impacted in the PFC. Gene modules protected from the effects of selection may help to eliminate certain mechanisms from significant involvement in risk for MA intake. One such module was enriched in genes with dopamine-associated annotations. Overall, the data suggest that mitochondrial function and glutamate-mediated synaptic plasticity have key roles in the outcomes of selective breeding for high versus low levels of MA intake. Full article
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Open AccessArticle
Neural Sensitivity to Mutual Information in Intermediate-Complexity Face Features Changes during Childhood
Brain Sci. 2019, 9(7), 154; https://doi.org/10.3390/brainsci9070154
Received: 14 May 2019 / Revised: 25 June 2019 / Accepted: 25 June 2019 / Published: 28 June 2019
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Abstract
One way in which face recognition develops during infancy and childhood is with regard to the visual information that contributes most to recognition judgments. Adult face recognition depends on critical features spanning a hierarchy of complexity, including low-level, intermediate, and high-level visual information. [...] Read more.
One way in which face recognition develops during infancy and childhood is with regard to the visual information that contributes most to recognition judgments. Adult face recognition depends on critical features spanning a hierarchy of complexity, including low-level, intermediate, and high-level visual information. To date, the development of adult-like information biases for face recognition has focused on low-level features, which are computationally well-defined but low in complexity, and high-level features, which are high in complexity, but not defined precisely. To complement this existing literature, we examined the development of children’s neural responses to intermediate-level face features characterized using mutual information. Specifically, we examined children’s and adults’ sensitivity to varying levels of category diagnosticity at the P100 and N170 components. We found that during middle childhood, sensitivity to mutual information shifts from early components to later ones, which may indicate a critical restructuring of face recognition mechanisms that takes place over several years. This approach provides a useful bridge between the study of low- and high-level visual features for face recognition and suggests many intriguing questions for further investigation. Full article
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Open AccessPerspective
Neural Foundations of Ayres Sensory Integration®
Brain Sci. 2019, 9(7), 153; https://doi.org/10.3390/brainsci9070153
Received: 11 June 2019 / Revised: 26 June 2019 / Accepted: 27 June 2019 / Published: 28 June 2019
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Abstract
Sensory integration, now trademarked as Ayres Sensory Integration® or ASI, is based on principles of neuroscience and provides a framework for understanding the contributions of the sensory and motor foundations of human behavior. The theory and practice of ASI continues to evolve [...] Read more.
Sensory integration, now trademarked as Ayres Sensory Integration® or ASI, is based on principles of neuroscience and provides a framework for understanding the contributions of the sensory and motor foundations of human behavior. The theory and practice of ASI continues to evolve as greater understanding of the neurobiology of human behavior emerges. In this paper we examine core constructs of ASI identified in the seminal work of Dr. Jean Ayres, and present current neuroscience research that underlies the main patterns of sensory integration function and dysfunction. We consider how current research verifies and clarifies Ayres’ propositions by describing functions of the vestibular, proprioceptive, and tactile sensory systems, and exploring their relationships to ocular, postural, bilateral integration, praxis, and sensory modulation. We close by proposing neuroplasticity as the mechanisms underlying change as a result of ASI intervention. Full article
(This article belongs to the Special Issue Brain Mechanisms of Sensory Processing Disorder)
Open AccessBrief Report
Rapid Communication: Plasma Interleukin-35 in Children with Autism
Brain Sci. 2019, 9(7), 152; https://doi.org/10.3390/brainsci9070152
Received: 31 May 2019 / Revised: 21 June 2019 / Accepted: 24 June 2019 / Published: 27 June 2019
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Abstract
In autism spectrum disorders (ASD) many individuals have co-morbid immune dysregulation that can lead to inflammation in the brain and periphery. The novel cytokine interleukin (IL)-35 has described anti-inflammatory properties; however, the plasma levels of IL-35 in children with ASD have never been [...] Read more.
In autism spectrum disorders (ASD) many individuals have co-morbid immune dysregulation that can lead to inflammation in the brain and periphery. The novel cytokine interleukin (IL)-35 has described anti-inflammatory properties; however, the plasma levels of IL-35 in children with ASD have never been investigated. The plasma levels of IL-35 were measured by an enzyme-linked immunosorbent assay in 30 children with ASD and 39 typically developing (TD) controls. In the current study, we found that plasma IL-35 levels were significantly decreased in children with ASD compared with TD children. Furthermore, lower IL-35 levels were associated with worse behaviors as assessed using the aberrant behavior checklist. These findings are in line with other observations of decreased regulatory cytokines such as transforming growth factor beta and IL-10 in ASD, and associations with severity of behaviors. In conclusion, regulating the expression of IL-35 may provide a new possible target for the treatment of immune issues in ASD to address an imbalance between pro- and anti-inflammatory signals that alter the behavioral phenotype. Full article
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Open AccessArticle
Effect of a Mental Stimulation Program of Computer and Internet Learning on Cognitive Functions and Wellbeing in Older Community-Dwelling Mexicans
Brain Sci. 2019, 9(7), 151; https://doi.org/10.3390/brainsci9070151
Received: 13 May 2019 / Revised: 23 June 2019 / Accepted: 24 June 2019 / Published: 27 June 2019
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Abstract
Background: It has been reported that Mental Stimulation (MS) has a positive effect on cognitive functions and wellbeing. In this sense, different training activities have been proposed for MS such as theater, learning a new language, playing a musical instrument and computing, however, [...] Read more.
Background: It has been reported that Mental Stimulation (MS) has a positive effect on cognitive functions and wellbeing. In this sense, different training activities have been proposed for MS such as theater, learning a new language, playing a musical instrument and computing, however, there are few studies on older adults in Latin American countries. For this reason, the purpose of the present study was to determine the effect of a mental stimulation program (MSP) of computer and Internet learning on cognitive functions and wellbeing in older community-dwelling Mexicans. Method: A quasi-experimental pilot study was carried out in a convenience sample of 27 adults aged 60 to 69 years, without knowledge of the use of computers and Internet, without chronic non-communicable diseases, depression or cognitive impairment. Two groups were formed: (i) experimental (EG), n = 16 and (ii) control (CG), n = 11. The EG participated in an MSP in which 20 theoretical/practical sessions of two hours each were given, two times a week, on computer and Internet. The CG did not participate in any scheduled activity. All participants were measured before and after the intervention program in processing speed (PS), cognitive inhibition (CI), working and episodicmemory (WM and EM), visuospatial processing (VP), life satisfaction (LS) and positive and negative emotions (PE and NE). Results: After participation in the MSP, the EG showed significantly higher scores on the EM and VP tests compared to the CG (p < 0.05). Conclusions: Our findings suggest that an MSP of computer and Internet learning improves episodicmemory and visuospatial processing in older community-dwelling Mexicans. Full article
(This article belongs to the collection Collection on Cognitive Neuroscience)
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Open AccessArticle
Applying a Sensing-Enabled System for Ensuring Safe Anterior Cingulate Deep Brain Stimulation for Pain
Brain Sci. 2019, 9(7), 150; https://doi.org/10.3390/brainsci9070150
Received: 22 May 2019 / Revised: 17 June 2019 / Accepted: 25 June 2019 / Published: 26 June 2019
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Abstract
Deep brain stimulation (DBS) of the anterior cingulate cortex (ACC) was offered to chronic pain patients who had exhausted medical and surgical options. However, several patients developed recurrent seizures. This work was conducted to assess the effect of ACC stimulation on the brain [...] Read more.
Deep brain stimulation (DBS) of the anterior cingulate cortex (ACC) was offered to chronic pain patients who had exhausted medical and surgical options. However, several patients developed recurrent seizures. This work was conducted to assess the effect of ACC stimulation on the brain activity and to guide safe DBS programming. A sensing-enabled neurostimulator (Activa PC + S) allowing wireless recording through the stimulating electrodes was chronically implanted in three patients. Stimulation patterns with different amplitude levels and variable ramping rates were tested to investigate whether these patterns could provide pain relief without triggering after-discharges (ADs) within local field potentials (LFPs) recorded in the ACC. In the absence of ramping, AD activity was detected following stimulation at amplitude levels below those used in chronic therapy. Adjustment of stimulus cycling patterns, by slowly ramping on/off (8-s ramp duration), was able to prevent ADs at higher amplitude levels while maintaining effective pain relief. The absence of AD activity confirmed from the implant was correlated with the absence of clinical seizures. We propose that AD activity in the ACC could be a biomarker for the likelihood of seizures in these patients, and the application of sensing-enabled techniques has the potential to advance safer brain stimulation therapies, especially in novel targets. Full article
(This article belongs to the Special Issue Neuromodulation for Intractable Pain)
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