Open AccessReview
Physical Activity: A Viable Way to Reduce the Risks of Mild Cognitive Impairment, Alzheimer’s Disease, and Vascular Dementia in Older Adults
Brain Sci. 2017, 7(2), 22; doi:10.3390/brainsci7020022 -
Abstract
A recent alarming rise of neurodegenerative diseases in the developed world is one of the major medical issues affecting older adults. In this review, we provide information about the associations of physical activity (PA) with major age-related neurodegenerative diseases and syndromes, including Alzheimer’s
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A recent alarming rise of neurodegenerative diseases in the developed world is one of the major medical issues affecting older adults. In this review, we provide information about the associations of physical activity (PA) with major age-related neurodegenerative diseases and syndromes, including Alzheimer’s disease, vascular dementia, and mild cognitive impairment. We also provide evidence of PA’s role in reducing the risks of these diseases and helping to improve cognitive outcomes in older adults. Finally, we describe some potential mechanisms by which this protective effect occurs, providing guidelines for future research. Full article
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Open AccessArticle
Diffusion Assessment of Cortical Changes, Induced by Traumatic Spinal Cord Injury
Brain Sci. 2017, 7(2), 21; doi:10.3390/brainsci7020021 -
Abstract
Promising treatments are being developed to promote functional recovery after spinal cord injury (SCI). Magnetic resonance imaging, specifically Diffusion Tensor Imaging (DTI) has been shown to non-invasively measure both axonal and myelin integrity following traumatic brain and SCI. A novel data-driven model-selection algorithm
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Promising treatments are being developed to promote functional recovery after spinal cord injury (SCI). Magnetic resonance imaging, specifically Diffusion Tensor Imaging (DTI) has been shown to non-invasively measure both axonal and myelin integrity following traumatic brain and SCI. A novel data-driven model-selection algorithm known as Diffusion Basis Spectrum Imaging (DBSI) has been proposed to more accurately delineate white matter injury. The objective of this study was to investigate whether DTI/DBSI changes that extend to level of the cerebral peduncle and internal capsule following a SCI could be correlated with clinical function. A prospective non-randomized cohort of 23 patients with chronic spinal cord injuries and 17 control subjects underwent cranial diffusion weighted imaging, followed by whole brain DTI and DBSI computations. Region-based analyses were performed on cerebral peduncle and internal capsule. Three subgroups of patients were included in the region-based analysis. Tract-Based Spatial Statistics (TBSS) was also applied to allow whole-brain white matter analysis between controls and all patients. Functional assessments were made using International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) as modified by the American Spinal Injury Association (ASIA) Scale. Whole brain white matter analysis using TBSS finds no statistical difference between controls and all patients. Only cervical ASIA A/B patients in cerebral peduncle showed differences from controls in DTI and DBSI results with region-based analysis. Cervical ASIA A/B SCI patients had higher levels of axonal injury and edema/tissue loss as measured by DBSI at the level of the cerebral peduncle. DTI Fractional Anisotropy (FA), Axial Diffusivity (AD) and Radial Diffusivity (RD) was able to detect differences in cervical ASIA A/B patients, but were non-specific to pathologies. Increased water fraction indicated by DBSI non-restricted isotropic diffusion fraction in the cerebral peduncle, explains the simultaneously increased DTI AD and DTI RD values. Our results further demonstrate the utility of DTI to detect disruption in axonal integrity in white matter, yet a clear shortcoming in differentiating true axonal injury from inflammation/tissue loss. Our results suggest a preservation of axonal integrity at the cortical level and has implications for future regenerative clinical trials. Full article
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Open AccessArticle
The Effect of the Human Peptide GHK on Gene Expression Relevant to Nervous System Function and Cognitive Decline
Brain Sci. 2017, 7(2), 20; doi:10.3390/brainsci7020020 -
Abstract
Neurodegeneration, the progressive death of neurons, loss of brain function, and cognitive decline is an increasing problem for senior populations. Its causes are poorly understood and therapies are largely ineffective. Neurons, with high energy and oxygen requirements, are especially vulnerable to detrimental factors,
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Neurodegeneration, the progressive death of neurons, loss of brain function, and cognitive decline is an increasing problem for senior populations. Its causes are poorly understood and therapies are largely ineffective. Neurons, with high energy and oxygen requirements, are especially vulnerable to detrimental factors, including age-related dysregulation of biochemical pathways caused by altered expression of multiple genes. GHK (glycyl-l-histidyl-l-lysine) is a human copper-binding peptide with biological actions that appear to counter aging-associated diseases and conditions. GHK, which declines with age, has health promoting effects on many tissues such as chondrocytes, liver cells and human fibroblasts, improves wound healing and tissue regeneration (skin, hair follicles, stomach and intestinal linings, boney tissue), increases collagen, decorin, angiogenesis, and nerve outgrowth, possesses anti-oxidant, anti-inflammatory, anti-pain and anti-anxiety effects, increases cellular stemness and the secretion of trophic factors by mesenchymal stem cells. Studies using the Broad Institute Connectivity Map show that GHK peptide modulates expression of multiple genes, resetting pathological gene expression patterns back to health. GHK has been recommended as a treatment for metastatic cancer, Chronic Obstructive Lung Disease, inflammation, acute lung injury, activating stem cells, pain, and anxiety. Here, we present GHK’s effects on gene expression relevant to the nervous system health and function. Full article
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Open AccessReview
Surgical Neurostimulation for Spinal Cord Injury
Brain Sci. 2017, 7(2), 18; doi:10.3390/brainsci7020018 -
Abstract
Traumatic spinal cord injury (SCI) is a devastating neurological condition characterized by a constellation of symptoms including paralysis, paraesthesia, pain, cardiovascular, bladder, bowel and sexual dysfunction. Current treatment for SCI involves acute resuscitation, aggressive rehabilitation and symptomatic treatment for complications. Despite the progress
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Traumatic spinal cord injury (SCI) is a devastating neurological condition characterized by a constellation of symptoms including paralysis, paraesthesia, pain, cardiovascular, bladder, bowel and sexual dysfunction. Current treatment for SCI involves acute resuscitation, aggressive rehabilitation and symptomatic treatment for complications. Despite the progress in scientific understanding, regenerative therapies are lacking. In this review, we outline the current state and future potential of invasive and non-invasive neuromodulation strategies including deep brain stimulation (DBS), spinal cord stimulation (SCS), motor cortex stimulation (MCS), transcutaneous direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) in the context of SCI. We consider the ability of these therapies to address pain, sensorimotor symptoms and autonomic dysregulation associated with SCI. In addition to the potential to make important contributions to SCI treatment, neuromodulation has the added ability to contribute to our understanding of spinal cord neurobiology and the pathophysiology of SCI. Full article
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Open AccessArticle
Reducing Fall Risk with Combined Motor and Cognitive Training in Elderly Fallers
Brain Sci. 2017, 7(2), 19; doi:10.3390/brainsci7020019 -
Abstract
Background. Falling is a major clinical problem in elderly people, demanding effective solutions. At present, the only effective intervention is motor training of balance and strength. Executive function-based training (EFt) might be effective at preventing falls according to evidence showing a relationship between
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Background. Falling is a major clinical problem in elderly people, demanding effective solutions. At present, the only effective intervention is motor training of balance and strength. Executive function-based training (EFt) might be effective at preventing falls according to evidence showing a relationship between executive functions and gait abnormalities. The aim was to assess the effectiveness of a motor and a cognitive treatment developed within the EU co-funded project I-DONT-FALL. Methods. In a sample of 481 elderly people at risk of falls recruited in this multicenter randomised controlled trial, the effectiveness of a motor treatment (pure motor or mixed with EFt) of 24 one-hour sessions delivered through an i-Walker with a non-motor treatment (pure EFt or control condition) was evaluated. Similarly, a 24 one-hour session cognitive treatment (pure EFt or mixed with motor training), delivered through a touch-screen computer was compared with a non-cognitive treatment (pure motor or control condition). Results. Motor treatment, particularly when mixed with EFt, reduced significantly fear of falling (F(1,478) = 6.786, p = 0.009) although to a limited extent (ES −0.25) restricted to the period after intervention. Conclusions. This study suggests the effectiveness of motor treatment empowered by EFt in reducing fear of falling. Full article
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Open AccessArticle
Spatial Impairment and Memory in Genetic Disorders: Insights from Mouse Models
Brain Sci. 2017, 7(2), 17; doi:10.3390/brainsci7020017 -
Abstract
Research across the cognitive and brain sciences has begun to elucidate some of the processes that guide navigation and spatial memory. Boundary geometry and featural landmarks are two distinct classes of environmental cues that have dissociable neural correlates in spatial representation and follow
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Research across the cognitive and brain sciences has begun to elucidate some of the processes that guide navigation and spatial memory. Boundary geometry and featural landmarks are two distinct classes of environmental cues that have dissociable neural correlates in spatial representation and follow different patterns of learning. Consequently, spatial navigation depends both on the type of cue available and on the type of learning provided. We investigated this interaction between spatial representation and memory by administering two different tasks (working memory, reference memory) using two different environmental cues (rectangular geometry, striped landmark) in mouse models of human genetic disorders: Prader-Willi syndrome (PWScrm+/p− mice, n = 12) and Beta-catenin mutation (Thr653Lys-substituted mice, n = 12). This exploratory study provides suggestive evidence that these models exhibit different abilities and impairments in navigating by boundary geometry and featural landmarks, depending on the type of memory task administered. We discuss these data in light of the specific deficits in cognitive and brain function in these human syndromes and their animal model counterparts. Full article
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Open AccessArticle
NLRP12 Inflammasome Expression in the Rat Brain in Response to LPS during Morphine Tolerance
Brain Sci. 2017, 7(2), 14; doi:10.3390/brainsci7020014 -
Abstract
Morphine, an effective but addictive analgesic, can profoundly affect the inflammatory response to pathogens, and long-term use can result in morphine tolerance. Inflammasomes are protein complexes involved in the inflammatory response. The nucleotide-binding oligomerization domain-like receptor (NLR) Family Pyrin Domain Containing (NLRP) 12
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Morphine, an effective but addictive analgesic, can profoundly affect the inflammatory response to pathogens, and long-term use can result in morphine tolerance. Inflammasomes are protein complexes involved in the inflammatory response. The nucleotide-binding oligomerization domain-like receptor (NLR) Family Pyrin Domain Containing (NLRP) 12 (NLRP12) inflammasome has been reported to have anti-inflammatory activity. In this study, we examined the expression of NLRP12 inflammasome related genes in the adult F344 rat brain in response to the bacterial endotoxin lipopolysaccharide (LPS) in the presence and absence of morphine tolerance. Morphine tolerance was elicited using the 2 + 4 morphine-pelleting protocol. On Day 1, the rats were pelleted subcutaneously with 2 pellets of morphine (75 mg/pellet) or a placebo; on Days 2 and 4 pellets were given. On Day 5, the animals were randomly assigned to receive either 250 µg/kg LPS or saline (i.p.). The expression of 84 inflammasome related genes in the rat brain was examined using a Ploymerase Chain Reaction (PCR) array. In response to LPS, there was a significant increase in the expression of the pro-inflammatory cytokine/chemokine genes interleukin-1 beta (Il-1β), interleukin-6 (Il-6), C-C motif chemokine ligand 2 (Ccl2), C-C motif chemokine ligand 7 (Ccl7), C-X-C motif chemokine ligand 1 (Cxcl1), and C-X-C motif chemokine ligand 3 (Cxcl3) and a significant decrease in the anti-inflammatory NLRP12 gene in both morphine-tolerant and placebo-control rats compared to saline-treated rats, although the changes were greater in the placebo-control animals. The Library of Integrated Network-Based Cellular Signatures’ (LINCS) connectivity map was used to analyze the list of affected genes to identify potential targets associated with the interactions of LPS and morphine tolerance. Our data indicate that, in the morphine tolerant state, the expression of NLRP12 and its related genes is altered in response to LPS and that the Vacuolar protein-sorting-associated protein 28 (VPS28), which is involved in the transport and sorting of proteins into sub-cellular vesicles, may be the key regulator of these alterations. Full article
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Open AccessArticle
Effect of Experimental Hand Pain on Training-Induced Changes in Motor Performance and Corticospinal Excitability
Brain Sci. 2017, 7(2), 15; doi:10.3390/brainsci7020015 -
Abstract
Pain influences plasticity within the sensorimotor system and the aim of this study was to assess the effect of pain on changes in motor performance and corticospinal excitability during training for a novel motor task. A total of 30 subjects were allocated to
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Pain influences plasticity within the sensorimotor system and the aim of this study was to assess the effect of pain on changes in motor performance and corticospinal excitability during training for a novel motor task. A total of 30 subjects were allocated to one of two groups (Pain, NoPain) and performed ten training blocks of a visually-guided isometric pinch task. Each block consisted of 15 force sequences, and subjects modulated the force applied to a transducer in order to reach one of five target forces. Pain was induced by applying capsaicin cream to the thumb. Motor performance was assessed by a skill index that measured shifts in the speed–accuracy trade-off function. Neurophysiological measures were taken from the first dorsal interosseous using transcranial magnetic stimulation. Overall, the Pain group performed better throughout the training (p = 0.03), but both groups showed similar improvements across training blocks (p < 0.001), and there was no significant interaction. Corticospinal excitability in the NoPain group increased halfway through the training, but this was not observed in the Pain group (Time × Group interaction; p = 0.01). These results suggest that, even when pain does not negatively impact on the acquisition of a novel motor task, it can affect training-related changes in corticospinal excitability. Full article
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Open AccessArticle
Inhibitory Control under Threat: The Role of Spontaneous Eye Blinks in Post-Traumatic Stress Disorder
Brain Sci. 2017, 7(2), 16; doi:10.3390/brainsci7020016 -
Abstract
This study is the first to explore spontaneous eye blink rate (sEBR) in individuals with post-traumatic stress disorder (PTSD). We investigated the connection between the magnitude of flanker interference in PTSD participants and sEBR during performance on a modified version of the Eriksen
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This study is the first to explore spontaneous eye blink rate (sEBR) in individuals with post-traumatic stress disorder (PTSD). We investigated the connection between the magnitude of flanker interference in PTSD participants and sEBR during performance on a modified version of the Eriksen flanker task. As a peripheral measure of cognitive control and dopaminergic function, sEBR may illuminate the relationship between PTSD and executive function. Findings revealed a positive relationship between sEBR and flanker interference in participants diagnosed with PTSD, to both threat-related and neutral stimuli, whereas this relationship was negative in participants exposed to trauma but without PTSD and in healthy controls. Although our results are suggestive of sEBR as a potential physiological index of emotional management in PTSD, most of the correlations were not significant, indicating that further research with a larger sample is needed. Full article
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Open AccessReview
Overview of Traumatic Brain Injury: An Immunological Context
Brain Sci. 2017, 7(1), 11; doi:10.3390/brainsci7010011 -
Abstract
Traumatic brain injury (TBI) afflicts people of all ages and genders, and the severity of injury ranges from concussion/mild TBI to severe TBI. Across all spectrums, TBI has wide-ranging, and variable symptomology and outcomes. Treatment options are lacking for the early neuropathology associated
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Traumatic brain injury (TBI) afflicts people of all ages and genders, and the severity of injury ranges from concussion/mild TBI to severe TBI. Across all spectrums, TBI has wide-ranging, and variable symptomology and outcomes. Treatment options are lacking for the early neuropathology associated with TBIs and for the chronic neuropathological and neurobehavioral deficits. Inflammation and neuroinflammation appear to be major mediators of TBI outcomes. These systems are being intensively studies using animal models and human translational studies, in the hopes of understanding the mechanisms of TBI, and developing therapeutic strategies to improve the outcomes of the millions of people impacted by TBIs each year. This manuscript provides an overview of the epidemiology and outcomes of TBI, and presents data obtained from animal and human studies focusing on an inflammatory and immunological context. Such a context is timely, as recent studies blur the traditional understanding of an “immune-privileged” central nervous system. In presenting the evidence for specific, adaptive immune response after TBI, it is hoped that future studies will be interpreted using a broader perspective that includes the contributions of the peripheral immune system, to central nervous system disorders, notably TBI and post-traumatic syndromes. Full article
Open AccessArticle
A Genetic-Based Feature Selection Approach in the Identification of Left/Right Hand Motor Imagery for a Brain-Computer Interface
Brain Sci. 2017, 7(1), 12; doi:10.3390/brainsci7010012 -
Abstract
Electroencephalography is a non-invasive measure of the brain electrical activity generated by millions of neurons. Feature extraction in electroencephalography analysis is a core issue that may lead to accurate brain mental state classification. This paper presents a new feature selection method that improves
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Electroencephalography is a non-invasive measure of the brain electrical activity generated by millions of neurons. Feature extraction in electroencephalography analysis is a core issue that may lead to accurate brain mental state classification. This paper presents a new feature selection method that improves left/right hand movement identification of a motor imagery brain-computer interface, based on genetic algorithms and artificial neural networks used as classifiers. Raw electroencephalography signals are first preprocessed using appropriate filtering. Feature extraction is carried out afterwards, based on spectral and temporal signal components, and thus a feature vector is constructed. As various features might be inaccurate and mislead the classifier, thus degrading the overall system performance, the proposed approach identifies a subset of features from a large feature space, such that the classifier error rate is reduced. Experimental results show that the proposed method is able to reduce the number of features to as low as 0.5% (i.e., the number of ignored features can reach 99.5%) while improving the accuracy, sensitivity, specificity, and precision of the classifier. Full article
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Open AccessArticle
The Anterior Prefrontal Cortex and the Hippocampus Are Negatively Correlated during False Memories
Brain Sci. 2017, 7(1), 13; doi:10.3390/brainsci7010013 -
Abstract
False memories commonly activate the anterior/dorsolateral prefrontal cortex (A/DLPFC) and the hippocampus. These regions are assumed to work in concert during false memories, which would predict a positive correlation between the magnitudes of activity in these regions across participants. However, the A/DLPFC may
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False memories commonly activate the anterior/dorsolateral prefrontal cortex (A/DLPFC) and the hippocampus. These regions are assumed to work in concert during false memories, which would predict a positive correlation between the magnitudes of activity in these regions across participants. However, the A/DLPFC may also inhibit the hippocampus, which would predict a negative correlation between the magnitudes of activity in these regions. In the present functional magnetic resonance imaging (fMRI) study, during encoding, participants viewed abstract shapes in the left or right visual field. During retrieval, participants classified each old shape as previously in the “left” or “right” visual field followed by an “unsure”–“sure”–“very sure” confidence rating. The contrast of left-hits and left-misses produced two activations in the hippocampus and three activations in the left A/DLPFC. For each participant, activity associated with false memories (right–“left”–“very sure” responses) from the two hippocampal regions was plotted as a function of activity in each A/DLPFC region. Across participants, for one region in the left anterior prefrontal cortex, there was a negative correlation between the magnitudes of activity in this region and the hippocampus. This suggests that the anterior prefrontal cortex might inhibit the hippocampus during false memories and that participants engage either the anterior prefrontal cortex or the hippocampus during false memories. Full article
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Open AccessReview
Contributions of Letter-Speech Sound Learning and Visual Print Tuning to Reading Improvement: Evidence from Brain Potential and Dyslexia Training Studies
Brain Sci. 2017, 7(1), 10; doi:10.3390/brainsci7010010 -
Abstract
We use a neurocognitive perspective to discuss the contribution of learning letter-speech sound (L-SS) associations and visual specialization in the initial phases of reading in dyslexic children. We review findings from associative learning studies on related cognitive skills important for establishing and consolidating
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We use a neurocognitive perspective to discuss the contribution of learning letter-speech sound (L-SS) associations and visual specialization in the initial phases of reading in dyslexic children. We review findings from associative learning studies on related cognitive skills important for establishing and consolidating L-SS associations. Then we review brain potential studies, including our own, that yielded two markers associated with reading fluency. Here we show that the marker related to visual specialization (N170) predicts word and pseudoword reading fluency in children who received additional practice in the processing of morphological word structure. Conversely, L-SS integration (indexed by mismatch negativity (MMN)) may only remain important when direct orthography to semantic conversion is not possible, such as in pseudoword reading. In addition, the correlation between these two markers supports the notion that multisensory integration facilitates visual specialization. Finally, we review the role of implicit learning and executive functions in audiovisual learning in dyslexia. Implications for remedial research are discussed and suggestions for future studies are presented. Full article
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Open AccessReview
Single Electrode Deep Brain Stimulation with Dual Targeting at Dual Frequency for the Treatment of Chronic Pain: A Case Series and Review of the Literature
Brain Sci. 2017, 7(1), 9; doi:10.3390/brainsci7010009 -
Abstract
Deep Brain Stimulation (DBS) has been used to target many deep brain structures for the treatment of chronic pain. The periaqueductal grey and periventricular grey (PAG/PVG) is an effective target but results are variable, sometimes short-lived or subject to tolerance. The centromedian intra-laminar
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Deep Brain Stimulation (DBS) has been used to target many deep brain structures for the treatment of chronic pain. The periaqueductal grey and periventricular grey (PAG/PVG) is an effective target but results are variable, sometimes short-lived or subject to tolerance. The centromedian intra-laminar parafascicular complex (CMPf) modulates medial pain pathways and CMPf DBS may address the affective aspects of pain perception. Stimulation of multiple deep brain targets may offer a strategy to optimize management of patients with complex pain symptomatology. However, previous attempts to stimulate multiple targets requires multiple trajectories and considerable expense. Using a single electrode to stimulate multiple targets would help overcome these challenges. A pre-requisite of such a technique is the ability to use different stimulation parameters at different contacts simultaneously on the same electrode. We describe a novel technique in 3 patients with chronic pain syndromes for whom conventional medical and/or neuromodulation therapy had failed using a single electrode technique to stimulate PVG/PAG and CMPf at dual frequencies. Full article
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Open AccessFeature PaperArticle
Sex Differences in Neuromuscular Fatigability of the Knee Extensors Post-Stroke
Brain Sci. 2017, 7(1), 8; doi:10.3390/brainsci7010008 -
Abstract
Background and Purpose: Despite the implications of optimizing strength training post-stroke, little is known about the differences in fatigability between men and women with chronic stroke. The purpose of this study was to determine the sex differences in knee extensor muscle fatigability and
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Background and Purpose: Despite the implications of optimizing strength training post-stroke, little is known about the differences in fatigability between men and women with chronic stroke. The purpose of this study was to determine the sex differences in knee extensor muscle fatigability and potential mechanisms in individuals with stroke. Methods: Eighteen participants (10 men, eight women) with chronic stroke (≥6 months) and 23 (12 men, 11 women) nonstroke controls participated in the study. Participants performed an intermittent isometric contraction task (6 s contraction, 3 s rest) at 30% of maximal voluntary contraction (MVC) torque until failure to maintain the target torque. Electromyography was used to determine muscle activation and contractile properties were assessed with electrical stimulation of the quadriceps muscles. Results: Individuals with stroke had a briefer task duration (greater fatigability) than nonstroke individuals (24.1 ± 17 min vs. 34.9 ± 16 min). Men were more fatigable than women for both nonstroke controls and individuals with stroke (17.9 ± 9 min vs. 41.6 ± 15 min). Individuals with stroke had less fatigue-related changes in muscle contractile properties and women with stroke differed in their muscle activation strategy during the fatiguing contractions. Conclusions: Men and women fatigue differently post-stroke and this may be due to the way they neurally activate muscle groups. Full article
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Open AccessEditorial
Acknowledgement to Reviewers of Brain Sciences in 2016
Brain Sci. 2017, 7(1), 7; doi:10.3390/brainsci7010007 -
Abstract The editors of Brain Sciences would like to express their sincere gratitude to the following reviewers for assessing manuscripts in 2016.[...] Full article
Open AccessArticle
Relationships between GAT1 and PTSD, Depression, and Substance Use Disorder
Brain Sci. 2017, 7(1), 6; doi:10.3390/brainsci7010006 -
Abstract
Post-traumatic stress disorder (PTSD), Major Depressive Disorder (MDD), and Substance Use Disorder (SUD) have large public health impacts. Therefore, researchers have attempted to identify those at greatest risk for these phenotypes. PTSD, MDD, and SUD are in part genetically influenced. Additionally, genes in
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Post-traumatic stress disorder (PTSD), Major Depressive Disorder (MDD), and Substance Use Disorder (SUD) have large public health impacts. Therefore, researchers have attempted to identify those at greatest risk for these phenotypes. PTSD, MDD, and SUD are in part genetically influenced. Additionally, genes in the glutamate and gamma-aminobutyric acid (GABA) system are implicated in the encoding of emotional and fear memories, and thus may impact these phenotypes. The current study examined the associations of single nucleotide polymorphisms in GAT1 individually, and at the gene level, using a principal components (PC) approach, with PTSD, PTSD comorbid with MDD, and PTSD comorbid with SUD in 486 combat-exposed veterans.  Findings indicate that several GAT1 SNPs, as well as one of the GAT1 PCs, was associated with PTSD, with and without MDD and SUD comorbidity. The present study findings provide initial insights into one pathway by which shared genetic risk influences PTSD-MDD and PTSD-SUD comorbidities, and thus identify a high-risk group (based on genotype) on whom prevention and intervention efforts should be focused. Full article
Open AccessReview
Enduring, Sexually Dimorphic Impact of In Utero Exposure to Elevated Levels of Glucocorticoids on Midbrain Dopaminergic Populations
Brain Sci. 2017, 7(1), 5; doi:10.3390/brainsci7010005 -
Abstract
Glucocorticoid hormones (GCs) released from the fetal/maternal glands during late gestation are required for normal development of mammalian organs and tissues. Accordingly, synthetic glucocorticoids have proven to be invaluable in perinatal medicine where they are widely used to accelerate fetal lung maturation when
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Glucocorticoid hormones (GCs) released from the fetal/maternal glands during late gestation are required for normal development of mammalian organs and tissues. Accordingly, synthetic glucocorticoids have proven to be invaluable in perinatal medicine where they are widely used to accelerate fetal lung maturation when there is risk of pre-term birth and to promote infant survival. However, clinical and pre-clinical studies have demonstrated that inappropriate exposure of the developing brain to elevated levels of GCs, either as a result of clinical over-use or after stress-induced activation of the fetal/maternal adrenal cortex, is linked with significant effects on brain structure, neurological function and behaviour in later life. In order to understand the underlying neural processes, particular interest has focused on the midbrain dopaminergic systems, which are critical regulators of normal adaptive behaviours, cognitive and sensorimotor functions. Specifically, using a rodent model of GC exposure in late gestation (approximating human brain development at late second/early third trimester), we demonstrated enduring effects on the shape and volume of the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) (origins of the mesocorticolimbic and nigrostriatal dopaminergic pathways) on the topographical organisation and size of the dopaminergic neuronal populations and astrocytes within these nuclei and on target innervation density and neurochemical markers of dopaminergic transmission (receptors, transporters, basal and amphetamine-stimulated dopamine release at striatal and prefrontal cortical sites) that impact on the adult brain. The effects of antenatal GC treatment (AGT) were both profound and sexually-dimorphic, not only in terms of quantitative change but also qualitatively, with several parameters affected in the opposite direction in males and females. Although such substantial neurobiological changes might presage marked behavioural effects, in utero GC exposure had only a modest or no effect, depending on sex, on a range of conditioned and unconditioned behaviours known to depend on midbrain dopaminergic transmission. Collectively, these findings suggest that apparent behavioural normality in certain tests, but not others, arises from AGT-induced adaptations or compensatory mechanisms within the midbrain dopaminergic systems, which preserve some, but not all functions. Furthermore, the capacities for molecular adaptations to early environmental challenge are different, even opponent, in males and females, which may account for their differential resilience or failure to perform adequately in behavioural tests. Behavioural “normality” is thus achieved by the midbrain dopaminergic network operating outside its normal limits (in a state of allostasis), rendering it at greater risk to malfunction when challenged in later life. Sex-specific neurobiological programming of midbrain dopaminergic systems may, therefore, have psychopathological relevance for the sex bias commonly found in brain disorders associated with these systems, and which have a neurodevelopmental component, including schizophrenia, ADHD (attention/deficit hyperactivity disorders), autism, depression and substance abuse. Full article
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Open AccessCase Report
An Unusual Case of Post-Traumatic Headache Complicated by Intracranial Hypotension
Brain Sci. 2017, 7(1), 3; doi:10.3390/brainsci7010003 -
Abstract
We present a case of post-traumatic headache complicated by intracranial hypotension resulting in an acquired Chiari malformation and myelopathy with syringomyelia. This constellation of findings suggest a possible series of events that started with a traumatic cerebral spinal fluid (CSF) leak, followed by
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We present a case of post-traumatic headache complicated by intracranial hypotension resulting in an acquired Chiari malformation and myelopathy with syringomyelia. This constellation of findings suggest a possible series of events that started with a traumatic cerebral spinal fluid (CSF) leak, followed by descent of the cerebellar tonsils and disruption of CSF circulation that caused spinal cord swelling and syrinx. This unusual presentation of post-traumatic headache highlights the varying presentations and the potential sequelae of intracranial hypotension. In addition, the delayed onset of upper motor neuron symptoms along with initially normal head computerized tomography scan (CT) findings, beg the question of whether or not a post-traumatic headache warrants earlier magnetic resonance imaging (MRI). Full article
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Open AccessReview
The Interplay of Hippocampus and Ventromedial Prefrontal Cortex in Memory-Based Decision Making
Brain Sci. 2017, 7(1), 4; doi:10.3390/brainsci7010004 -
Abstract
Episodic memory and value-based decision making are two central and intensively studied research domains in cognitive neuroscience, but we are just beginning to understand how they interact to enable memory-based decisions. The two brain regions that have been associated with episodic memory and
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Episodic memory and value-based decision making are two central and intensively studied research domains in cognitive neuroscience, but we are just beginning to understand how they interact to enable memory-based decisions. The two brain regions that have been associated with episodic memory and value-based decision making are the hippocampus and the ventromedial prefrontal cortex, respectively. In this review article, we first give an overview of these brain–behavior associations and then focus on the mechanisms of potential interactions between the hippocampus and ventromedial prefrontal cortex that have been proposed and tested in recent neuroimaging studies. Based on those possible interactions, we discuss several directions for future research on the neural and cognitive foundations of memory-based decision making. Full article
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