[Cellular mechanisms of neuroplasticity].

PubMed

Bergado-Rosado, J A; Almaguer-Melian, W

To present a unified vision of the principal known mechanisms of neuroplasticity, emphasizing their universality. The concept of the central nervous system as an immutable entity has been considerably modified during the second half of the 20th century. Neuroplasticity, that is the ability of the brain regarding change and repair is expressed in different ways, from functional modifications of existing structures to the formation, by growth and proliferation, of new structures and neurons. This study considers the molecular and cellular mechanisms of neuroplastic phenomena and classifies them into two main groups: plasticity due to growth, including the mechanisms of axonal regeneration, collateralization and reactive synaptogenesis; and functional plasticity, which includes changes in the efficacy of synaptic transmission such as long-term potentiation and the activation of silent synapses. We also describe some of the relations of neuroplastic phenomena with disease of the central nervous system, together with examples of physiological, physical and pharmacological factors which may be used in future as therapeutic tools to stimulate and modulate neuroplasticity. Neuroplastic mechanisms show a high degree of phylogenetic and ontogenetic conservation. They are important both in the genesis of disorders and disease of the nervous system and for its repair after different types of damage and trauma. Modulation of neuroplastic mechanisms by physical and chemical agents would appear to be one of the most powerful therapeutic tools of restorative neurology.

Harnessing neuroplasticity: modern approaches and clinical future.

PubMed

Sasmita, Andrew Octavian; Kuruvilla, Joshua; Ling, Anna Pick Kiong

2018-05-04

Neurological diseases and injuries to the nervous system may cause inadvertent damage to neuronal and synaptic structures. Such phenomenon would lead to the development of neurological and neurodegenerative disorders which might affect memory, cognition and motoric functions. The body has various negative feedback systems which can induce beneficial neuroplastic changes in mediating some neuronal damage; however, such efforts are often not enough to ameliorate the derogatory changes. Articles discussing studies to induce beneficial neuroplastic changes were retrieved from the databases, National Center for Biotechnology Information (NCBI) and MEDLINE, and reviewed. This review highlights the significance of neuroplasticity in restoring neuronal functions and current advances in research to employ this positive cellular event by inducing synaptogenesis, neurogenesis, clearance of toxic amyloid beta (Aβ) and tau protein aggregates, or by providing neuroprotection. Compounds ranging from natural products (e.g. bilobalides, curcumin) to novel vaccines (e.g. AADvac1, RG7345) have been reported to induce long-lasting neuroplasticity in vitro and in vitro. Activity-dependent neuroplasticity is also inducible by regimens of exercises and therapies with instances in human studies proving major successes. Lastly, mechanical stimulation of brain regions through therapeutic hypothermia or deep brain stimulation has given insight on the larger scale of neuroplasticity within the nervous system. Harnessing neuroplasticity may not only offer an arm in the vast arsenal of approaches being taken to tackle neurological disorders, such as neurodegenerative diseases, but from ample evidence, it also has major implications in neuropsychological disorders.

Targeting acetylcholine receptor M3 prevents the progression of airway hyperreactivity in a mouse model of childhood asthma.

PubMed

Patel, Kruti R; Bai, Yan; Trieu, Kenneth G; Barrios, Juliana; Ai, Xingbin

2017-10-01

Asthma often progresses into adulthood from early-life episodes of adverse environmental exposures. However, how the injury to developing lungs contributes to the pathophysiology of persistent asthma remains poorly understood. In this study, we identified an age-related mechanism along the cholinergic nerve-airway smooth muscle (ASM) axis that underlies prolonged airway hyperreactivity (AHR) in mice. We showed that ASM continued to mature until ∼3 wk after birth. Coinciding with postnatal ASM maturation, there was a critical time window for the development of ASM hypercontractility after cholinergic stimulation. We found that allergen exposure in neonatal mice, but not in adult mice, elevated the level and activity of cholinergic nerves (termed neuroplasticity). We demonstrated that cholinergic neuroplasticity is necessary for the induction of persistent AHR after neonatal exposure during rescue assays in mice deficient in neuroplasticity. In addition, early intervention with cholinergic receptor muscarinic (ChRM)-3 blocker reversed the progression of AHR in the neonatal exposure model, whereas β2-adrenoceptor agonists had no such effect. Together, our findings demonstrate a functional relationship between cholinergic neuroplasticity and ASM contractile phenotypes that operates uniquely in early life to induce persistent AHR after allergen exposure. Targeting ChRM3 may have disease-modifying benefits in childhood asthma.-Patel, K. R., Bai, Y., Trieu, K. G., Barrios, J., Ai, X. Targeting acetylcholine receptor M3 prevents the progression of airway hyperreactivity in a mouse model of childhood asthma. © FASEB.

Neuroplasticity, Psychosocial Genomics, and the Biopsychosocial Paradigm in the 21st Century

ERIC Educational Resources Information Center

Garland, Eric L.; Howard, Matthew Owen

2009-01-01

The biopsychosocial perspective is a foundation of social work theory and practice. Recent research on neuroplasticity and psychosocial genomics lends compelling support to this perspective by elucidating mechanisms through which psychosocial forces shape neurobiology. Investigations of neuroplasticity demonstrate that the adult brain can continue…

Neuroplasticity in post-stroke gait recovery and noninvasive brain stimulation

PubMed Central

Xu, Yi; Hou, Qing-hua; Russell, Shawn D.; Bennett, Bradford C.; Sellers, Andrew J.; Lin, Qiang; Huang, Dong-feng

2015-01-01

Gait disorders drastically affect the quality of life of stroke survivors, making post-stroke rehabilitation an important research focus. Noninvasive brain stimulation has potential in facilitating neuroplasticity and improving post-stroke gait impairment. However, a large inter-individual variability in the response to noninvasive brain stimulation interventions has been increasingly recognized. We first review the neurophysiology of human gait and post-stroke neuroplasticity for gait recovery, and then discuss how noninvasive brain stimulation techniques could be utilized to enhance gait recovery. While post-stroke neuroplasticity for gait recovery is characterized by use-dependent plasticity, it evolves over time, is idiosyncratic, and may develop maladaptive elements. Furthermore, noninvasive brain stimulation has limited reach capability and is facilitative-only in nature. Therefore, we recommend that noninvasive brain stimulation be used adjunctively with rehabilitation training and other concurrent neuroplasticity facilitation techniques. Additionally, when noninvasive brain stimulation is applied for the rehabilitation of gait impairment in stroke survivors, stimulation montages should be customized according to the specific types of neuroplasticity found in each individual. This could be done using multiple mapping techniques. PMID:26889202

Application of neuroplasticity theory through the use of the Feldenkrais Method(®) with a runner with scoliosis and hip and lumbar pain: A case report.

PubMed

Myers, Lori K

2016-04-01

Neuroplasticity theory has gained considerable attention in recent years in the professions of medicine, psychology and neuroscience. Most research on neuroplasticity has been in neurology focusing on stroke and other central nervous system disease and injury. Further research is necessary to advance the connection of neuroplasticity theory to musculoskeletal conditions and rehabilitation. The theory of neuroplasticity as it applies to the acquisition of new skills and modification of maladaptive, pain-perpetuating and inefficient movement patterns is fundamental to the Feldenkrais Method. This case report demonstrates the application of neuroplasticity theory with the Feldenkrais Method as the primary intervention for a 42-year-old female runner with a history of adolescent idiopathic scoliosis who presented with hip and lumbar pain. The client had clinically meaningful improvements in pain intensity and the Global Rating of Change scale while meeting her goals to resume pain free running, repetitive stair climbing at work, and other leisure activities. Copyright © 2015 Elsevier Ltd. All rights reserved.

Neuroplasticity in the auditory system.

PubMed

Gil-Loyzaga, P

2005-01-01

An increasing interest on neuroplasticity and nerve regeneration within the auditory receptor and pathway has developed in recent years. The receptor and the auditory pathway are controlled by highly complex circuits that appear during embryonic development. During this early maturation process of the auditory sensory elements, we observe the development of two types of nerve fibers: permanent fibers that will remain to reach full-term maturity and other transient fibers that will ultimately disappear. Both stable and transitory fibers however, as well as developing sensory cells, express, and probably release, their respective neuro-transmitters that could be involved in neuroplasticity. Cell culture experiments have added significant information; the in vitro administration of glutamate or GABA to isolated spiral ganglion neurons clearly modified neural development. Neuroplasticity has been also found in the adult. Nerve regeneration and neuroplasticity have been demonstrated in the adult auditory receptors as well as throughout the auditory pathway. Neuroplasticity studies could prove interesting in the elaboration of current or future therapy strategies (e.g.: cochlear implants or stem cells), but also to really understand the pathogenesis of auditory or language diseases (e.g.: deafness, tinnitus, dyslexia, etc.).

The pharmacology of neuroplasticity induced by non-invasive brain stimulation: building models for the clinical use of CNS active drugs

PubMed Central

Nitsche, Michael A; Müller-Dahlhaus, Florian; Paulus, Walter; Ziemann, Ulf

2012-01-01

The term neuroplasticity encompasses structural and functional modifications of neuronal connectivity. Abnormal neuroplasticity is involved in various neuropsychiatric diseases, such as dystonia, epilepsy, migraine, Alzheimer's disease, fronto-temporal degeneration, schizophrenia, and post cerebral stroke. Drugs affecting neuroplasticity are increasingly used as therapeutics in these conditions. Neuroplasticity was first discovered and explored in animal experimentation. However, non-invasive brain stimulation (NIBS) has enabled researchers recently to induce and study similar processes in the intact human brain. Plasticity induced by NIBS can be modulated by pharmacological interventions, targeting ion channels, or neurotransmitters. Importantly, abnormalities of plasticity as studied by NIBS are directly related to clinical symptoms in neuropsychiatric diseases. Therefore, a core theme of this review is the hypothesis that NIBS-induced plasticity can explore and potentially predict the therapeutic efficacy of CNS-acting drugs in neuropsychiatric diseases. We will (a) review the basics of neuroplasticity, as explored in animal experimentation, and relate these to our knowledge about neuroplasticity induced in humans by NIBS techniques. We will then (b) discuss pharmacological modulation of plasticity in animals and humans. Finally, we will (c) review abnormalities of plasticity in neuropsychiatric diseases, and discuss how the combination of NIBS with pharmacological intervention may improve our understanding of the pathophysiology of abnormal plasticity in these diseases and their purposeful pharmacological treatment. PMID:22869014

Integrative Analysis of Disease Signatures Shows Inflammation Disrupts Juvenile Experience-Dependent Cortical Plasticity

PubMed Central

Smith, Milo R.; Burman, Poromendro

2016-01-01

Throughout childhood and adolescence, periods of heightened neuroplasticity are critical for the development of healthy brain function and behavior. Given the high prevalence of neurodevelopmental disorders, such as autism, identifying disruptors of developmental plasticity represents an essential step for developing strategies for prevention and intervention. Applying a novel computational approach that systematically assessed connections between 436 transcriptional signatures of disease and multiple signatures of neuroplasticity, we identified inflammation as a common pathological process central to a diverse set of diseases predicted to dysregulate plasticity signatures. We tested the hypothesis that inflammation disrupts developmental cortical plasticity in vivo using the mouse ocular dominance model of experience-dependent plasticity in primary visual cortex. We found that the administration of systemic lipopolysaccharide suppressed plasticity during juvenile critical period with accompanying transcriptional changes in a particular set of molecular regulators within primary visual cortex. These findings suggest that inflammation may have unrecognized adverse consequences on the postnatal developmental trajectory and indicate that treating inflammation may reduce the burden of neurodevelopmental disorders. PMID:28101530

Nongenomic Actions of 17-β Estradiol Restore Respiratory Neuroplasticity in Young Ovariectomized Female Rats

PubMed Central

Dougherty, Brendan J.; Kopp, Elizabeth S.

2017-01-01

Gonadal steroids modulate CNS plasticity, including phrenic long-term facilitation (pLTF), a form of spinal respiratory neuroplasticity resulting in increased phrenic nerve motor output following exposure to acute intermittent hypoxia (aIH; three 5 min episodes, 10.5% O2). Despite the importance of respiratory system neuroplasticity, and its dependence on estrogen in males, little is known about pLTF expression or mechanisms of estrogen signaling in females. Here, we tested the hypotheses that (1) pLTF expression in young, gonadally intact female rats would be expressed during estrous cycle stages in which 17β-estradiol (E2) is naturally high (e.g., proestrus vs estrus), (2) pLTF would be absent in ovariectomized (OVX) rats and in physiological conditions in which serum progesterone, but not E2, is elevated (e.g., lactating rats, 3–10 d postpartum), and (3) acute E2 administration would be sufficient to restore pLTF in OVX rats. Recordings of phrenic nerve activity in female Sprague Dawley rats (3–4 months) revealed a direct correlation between serum E2 levels and pLTF expression in cycling female rats. pLTF was abolished with OVX, but was re-established by acute E2 replacement (3 h, intraperitoneal). To identify underlying E2 signaling mechanisms, we intrathecally applied BSA-conjugated E2 over the spinal phrenic motor nucleus and found that pLTF expression was restored within 15 min, suggesting nongenomic E2 effects at membrane estrogen receptors. These data are the first to investigate the role of ovarian E2 in young cycling females, and to identify a role for nongenomic estrogen signaling in any form of respiratory system neuroplasticity. SIGNIFICANCE STATEMENT Exposure to acute intermittent hypoxia induces phrenic long-term facilitation (pLTF), a form of spinal respiratory motor plasticity that improves breathing in models of spinal cord injury. Although pathways leading to pLTF are well studied in males and estradiol (E2) is known to be required, it has seldom been investigated in females, and underlying mechanisms of E2 signaling are unknown in either sex. We found that while ovariectomy abolished pLTF, it could be restored by acute systemic E2, or by intraspinal application of the membrane-impermeable E2 (BSA-conjugated E2; 15 min). The ability of nongenomic estrogen signaling within the cervical spinal cord to recover respiratory neuroplasticity in disorders of respiratory insufficiency suggests that membrane estrogen receptors may represent novel therapeutic targets to restore breathing in both sexes. PMID:28592693

Reactive Oxygen Species-Mediated Loss of Synaptic Akt1 Signaling Leads to Deficient Activity-Dependent Protein Translation Early in Alzheimer's Disease.

PubMed

Ahmad, Faraz; Singh, Kunal; Das, Debajyoti; Gowaikar, Ruturaj; Shaw, Eisha; Ramachandran, Arathy; Rupanagudi, Khader Valli; Kommaddi, Reddy Peera; Bennett, David A; Ravindranath, Vijayalakshmi

2017-12-01

Synaptic deficits are known to underlie the cognitive dysfunction seen in Alzheimer's disease (AD). Generation of reactive oxygen species (ROS) by β-amyloid has also been implicated in AD pathogenesis. However, it is unclear whether ROS contributes to synaptic dysfunction seen in AD pathogenesis and, therefore, we examined whether altered redox signaling could contribute to synaptic deficits in AD. Activity dependent but not basal translation was impaired in synaptoneurosomes from 1-month old presymptomatic APP Swe /PS1ΔE9 (APP/PS1) mice, and this deficit was sustained till middle age (MA, 9-10 months). ROS generation leads to oxidative modification of Akt1 in the synapse and consequent reduction in Akt1-mechanistic target of rapamycin (mTOR) signaling, leading to deficiency in activity-dependent protein translation. Moreover, we found a similar loss of activity-dependent protein translation in synaptoneurosomes from postmortem AD brains. Loss of activity-dependent protein translation occurs presymptomatically early in the pathogenesis of AD. This is caused by ROS-mediated loss of pAkt1, leading to reduced synaptic Akt1-mTOR signaling and is rescued by overexpression of Akt1. ROS-mediated damage is restricted to the synaptosomes, indicating selectivity. We demonstrate that ROS-mediated oxidative modification of Akt1 contributes to synaptic dysfunction in AD, seen as loss of activity-dependent protein translation that is essential for synaptic plasticity and maintenance. Therapeutic strategies promoting Akt1-mTOR signaling at synapses may provide novel target(s) for disease-modifying therapy in AD. Antioxid. Redox Signal. 27, 1269-1280.

Old Dogs Learning New Tricks: Neuroplasticity Beyond the Juvenile Period

PubMed Central

Lillard, Angeline S.; Erisir, Alev

2014-01-01

Twenty years ago, the prevalent view in psychology was that although learning and the formation of new memories are lifelong occurrences, the neural changes associated with these events were all in the existing receptors. No new neural hardware, from synapses to neurons, was thought to appear after a protracted period early in life. In the past 20 years, another view has supplanted this one, showing that although the juvenile period is especially suited to neuroplastic adaptation, there is hard neuroplastic change later in life as well. We review a selection of evidence for this view from both animal and human models, showing how it reflects three principles of neuroplasticity: 1) earlier and later experience-induced changes to neuroarchitecture differ in degree more so than in type; 2) the types of experiences that lead to neuroplastic change narrow with age; and 3) differences in the amenability of neural circuitry to change result from basic differences in neuroarchitecture and neuroenvironment in different phases of development. PMID:24648605

Innovative strength training-induced neuroplasticity and increased muscle size and strength in children with spastic cerebral palsy: an experimenter-blind case study--three-month follow-up.

PubMed

Lee, Dong Ryul; Kim, Yun Hee; Kim, Dong A; Lee, Jung Ah; Hwang, Pil Woo; Lee, Min Jin; You, Sung Hyun

2014-01-01

In children with cerebral palsy (CP), the never-learned-to-use (NLTU) effect and underutilization suppress the normal development of cortical plasticity in the paretic limb, which further inhibits its functional use and increases associated muscle weakness. To highlight the effects of a novel comprehensive hand repetitive intensive strengthening training system on neuroplastic changes associated with upper extremity (UE) muscle strength and motor performance in children with spastic hemiplegic CP. Two children with spastic hemiplegic CP were recruited. Intervention with the comprehensive hand repetitive intensive strengthening training system was provided for 60 min a day, three times a week, for 10 weeks. Neuroplastic changes, muscle size, strength, and associated motor function were measured using functional magnetic resonance imaging (MRI), ultrasound imaging, and standardized motor tests, respectively. The functional MRI data showed that the comprehensive hand repetitive intensive strengthening training intervention produced measurable neuroplastic changes in the neural substrates associated with motor control and learning. These neuroplastic changes were associated with increased muscle size, strength and motor function. These results provide compelling evidence of neuroplastic changes and associated improvements in muscle size and motor function following innovative upper extremity strengthening exercise.

Characterizing synaptic protein development in human visual cortex enables alignment of synaptic age with rat visual cortex

PubMed Central

Pinto, Joshua G. A.; Jones, David G.; Williams, C. Kate; Murphy, Kathryn M.

2015-01-01

Although many potential neuroplasticity based therapies have been developed in the lab, few have translated into established clinical treatments for human neurologic or neuropsychiatric diseases. Animal models, especially of the visual system, have shaped our understanding of neuroplasticity by characterizing the mechanisms that promote neural changes and defining timing of the sensitive period. The lack of knowledge about development of synaptic plasticity mechanisms in human cortex, and about alignment of synaptic age between animals and humans, has limited translation of neuroplasticity therapies. In this study, we quantified expression of a set of highly conserved pre- and post-synaptic proteins (Synapsin, Synaptophysin, PSD-95, Gephyrin) and found that synaptic development in human primary visual cortex (V1) continues into late childhood. Indeed, this is many years longer than suggested by neuroanatomical studies and points to a prolonged sensitive period for plasticity in human sensory cortex. In addition, during childhood we found waves of inter-individual variability that are different for the four proteins and include a stage during early development (<1 year) when only Gephyrin has high inter-individual variability. We also found that pre- and post-synaptic protein balances develop quickly, suggesting that maturation of certain synaptic functions happens within the 1 year or 2 of life. A multidimensional analysis (principle component analysis) showed that most of the variance was captured by the sum of the four synaptic proteins. We used that sum to compare development of human and rat visual cortex and identified a simple linear equation that provides robust alignment of synaptic age between humans and rats. Alignment of synaptic ages is important for age-appropriate targeting and effective translation of neuroplasticity therapies from the lab to the clinic. PMID:25729353

Yoga- and meditation-based lifestyle intervention increases neuroplasticity and reduces severity of major depressive disorder: A randomized controlled trial.

PubMed

Tolahunase, Madhuri R; Sagar, Rajesh; Faiq, Muneeb; Dada, Rima

2018-01-01

Current interventions for major depressive disorder (MDD) are suboptimal, and only one third respond to them on initial treatment. Neuroplasticity theories are the basis for several emerging treatments. Evidence on the impact of yoga, a well-known mind-body intervention, on neuroplasticity in MDD is limited. To determine the effects of 12-week yoga- and meditation-based lifestyle intervention (YMLI) on depression severity and systemic biomarkers of neuroplasticity in adult MDD patients on routine drug treatment. A total of 58 MDD patients were randomized into yoga or control group. The severity of depression was assessed with Beck Depression Inventory-II scale (BDI-II). Blood samples were collected before and after intervention for the measurement of the biomarkers that characterize neuroplasticity, including mind-body communicative and cellular health biomarkers. There was a significant decrease [difference between means, (95% CI)] in BDI-II score [-5.83 (-7.27, -4.39), p < 0.001] and significant increase in BDNF (ng/ml) [5.48 (3.50, 7.46), p < 0.001] after YMLI compared to control group. YMLI significantly increased DHEAS, sirtuin 1, and telomerase activity levels, and decreased cortisol, and IL-6 levels, in addition to decreasing DNA damage and balancing oxidative stress. Multiple regression analyses were used to associate neuroplasticity biomarkers with depression severity. A 'post-intervention change in BDNF' x 'group' interaction indicated that yoga group had more BDNF in association with less BDI-II scores relative to controls. Increased sirtuin 1 and telomerase activity and decreased cortisol significantly predicted this association (all p < 0.05). These results suggest that decrease in depression severity after YMLI in MDD is associated with improved systemic biomarkers of neuroplasticity. Thus YMLI can be considered as a therapeutic intervention in MDD management.

Promoting Neuroplasticity for Motor Rehabilitation After Stroke: Considering the Effects of Aerobic Exercise and Genetic Variation on Brain-Derived Neurotrophic Factor

PubMed Central

Mang, Cameron S.; Campbell, Kristin L.; Ross, Colin J.D.

2013-01-01

Recovery of motor function after stroke involves relearning motor skills and is mediated by neuroplasticity. Recent research has focused on developing rehabilitation strategies that facilitate such neuroplasticity to maximize functional outcome poststroke. Although many molecular signaling pathways are involved, brain-derived neurotrophic factor (BDNF) has emerged as a key facilitator of neuroplasticity involved in motor learning and rehabilitation after stroke. Thus, rehabilitation strategies that optimize BDNF effects on neuroplasticity may be especially effective for improving motor function poststroke. Two potential poststroke rehabilitation strategies that consider the importance of BDNF are the use of aerobic exercise to enhance brain function and the incorporation of genetic information to individualize therapy. Converging evidence demonstrates that aerobic exercise increases BDNF production and consequently enhances learning and memory processes. Nevertheless, a common genetic variant reduces activity-dependent secretion of the BDNF protein. Thus, BDNF gene variation may affect response to motor rehabilitation training and potentially modulate the effects of aerobic exercise on neuroplasticity. This perspective article discusses evidence that aerobic exercise promotes neuroplasticity by increasing BDNF production and considers how aerobic exercise may facilitate the acquisition and retention of motor skills for poststroke rehabilitation. Next, the impact of the BDNF gene val66met polymorphism on motor learning and response to rehabilitation is explored. It is concluded that the effects of aerobic exercise on BDNF and motor learning may be better exploited if aerobic exercise is paired more closely in time with motor training. Additionally, information about BDNF genotype could provide insight into the type and magnitude of effects that aerobic exercise may have across individuals and potentially help guide an individualized prescription of aerobic exercise to enhance motor rehabilitation poststroke. PMID:23907078

Excessive endoplasmic reticulum stress and decreased neuroplasticity-associated proteins in prefrontal cortex of obese rats and the regulatory effects of aerobic exercise.

PubMed

Li, Feng; Liu, Bei Bei; Cai, Ming; Li, Jing Jing; Lou, Shu-Jie

2018-04-06

Studies have shown high fat diet induced obesity may cause cognition impairment and down-regulation of neuroplasticity-associated proteins, while aerobic exercise could improve that damage. Endoplasmic reticulum stress (ERS) has been reported to play a key role in regulating neuroplasticity-associated proteins expression, folding and post-translational modification in hippocampus of obese rodent models, however, the effects of ERS on neuroplasticity-associated proteins and possible underlying mechanisms in prefrontal cortex are not fully clear. In order to clarify changes of neuroplasticity-associated proteins and ERS in the prefrontal cortex of obese rats, male SD rats were fed on high fat diet for 8 weeks to establish the obese model. Then, 8 weeks of aerobic exercise treadmill intervention was arranged for the obese rats. Results showed that high fat diet induced obesity caused hyperlipidemia, and significantly promoted FATP1 expression in the prefrontal cortex, meanwhile, we found up-regulation of GRP78, p-PERK, p-eIF2α, caspase-12, CHOP, and Bax/Bcl-2, reflecting the activation of ERS and ERS-mediated apoptosis. Moreover, reduced BDNF and SYN was found in obese rats. However, FATP1, GRP78, p-PERK, p-eIF2α, caspase-12, CHOP, and Bax/Bcl-2 expressions were obviously reversed by aerobic exercise intervention. These results suggested that dietary obesity could induce Prefrontal ERS in SD rats and excessive ERS may play a critical role in decreasing the levels of neuroplasticity-associated proteins. Moreover, aerobic exercise could relieve ERS, thus promoted the expression of neuroplasticity-associated proteins. Copyright © 2018. Published by Elsevier Inc.

Peripheral nerve injuries, pain, and neuroplasticity.

PubMed

Osborne, Natalie R; Anastakis, Dimitri J; Davis, Karen D

Peripheral nerve injuries (PNIs) cause both structural and functional brain changes that may be associated with significant sensorimotor abnormalities and pain. The aim of this narrative review is to provide hand therapists an overview of PNI-induced neuroplasticity and to explain how the brain changes following PNI, repair, and during rehabilitation. Toward this goal, we review key aspects of neuroplasticity and neuroimaging and discuss sensory testing techniques used to study neuroplasticity in PNI patients. We describe the specific brain changes that occur during the repair and recovery process of both traumatic (eg, transection) and nontraumatic (eg, compression) nerve injuries. We also explain how these changes contribute to common symptoms including hypoesthesia, hyperalgesia, cold sensitivity, and chronic neurogenic pain. In addition, we describe how maladaptive neuroplasticity as well as psychological and personality characteristics impacts treatment outcome. Greater understanding of the brain's contribution to symptoms in recovering PNI patients could help guide rehabilitation strategies and inform the development of novel techniques to counteract these maladaptive brain changes and ultimately improve outcomes. Copyright © 2018 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.

Neuroplasticity in the context of motor rehabilitation after stroke

PubMed Central

Dimyan, Michael A.; Cohen, Leonardo G.

2016-01-01

Approximately one-third of patients with stroke exhibit persistent disability after the initial cerebrovascular episode, with motor impairments accounting for most poststroke disability. Exercise and training have long been used to restore motor function after stroke. Better training strategies and therapies to enhance the effects of these rehabilitative protocols are currently being developed for poststroke disability. The advancement of our understanding of the neuroplastic changes associated with poststroke motor impairment and the innate mechanisms of repair is crucial to this endeavor. Pharmaceutical, biological and electrophysiological treatments that augment neuroplasticity are being explored to further extend the boundaries of poststroke rehabilitation. Potential motor rehabilitation therapies, such as stem cell therapy, exogenous tissue engineering and brain–computer interface technologies, could be integral in helping patients with stroke regain motor control. As the methods for providing motor rehabilitation change, the primary goals of poststroke rehabilitation will be driven by the activity and quality of life needs of individual patients. This Review aims to provide a focused overview of neuroplasticity associated with poststroke motor impairment, and the latest experimental interventions being developed to manipulate neuroplasticity to enhance motor rehabilitation. PMID:21243015

Neuroplasticity in the context of motor rehabilitation after stroke.

PubMed

Dimyan, Michael A; Cohen, Leonardo G

2011-02-01

Approximately one-third of patients with stroke exhibit persistent disability after the initial cerebrovascular episode, with motor impairments accounting for most poststroke disability. Exercise and training have long been used to restore motor function after stroke. Better training strategies and therapies to enhance the effects of these rehabilitative protocols are currently being developed for poststroke disability. The advancement of our understanding of the neuroplastic changes associated with poststroke motor impairment and the innate mechanisms of repair is crucial to this endeavor. Pharmaceutical, biological and electrophysiological treatments that augment neuroplasticity are being explored to further extend the boundaries of poststroke rehabilitation. Potential motor rehabilitation therapies, such as stem cell therapy, exogenous tissue engineering and brain-computer interface technologies, could be integral in helping patients with stroke regain motor control. As the methods for providing motor rehabilitation change, the primary goals of poststroke rehabilitation will be driven by the activity and quality of life needs of individual patients. This Review aims to provide a focused overview of neuroplasticity associated with poststroke motor impairment, and the latest experimental interventions being developed to manipulate neuroplasticity to enhance motor rehabilitation.

Molecular Mechanisms of Neuroplasticity: An Expanding Universe.

PubMed

Gulyaeva, N V

2017-03-01

Biochemical processes in synapses and other neuronal compartments underlie neuroplasticity (functional and structural alterations in the brain enabling adaptation to the environment, learning, memory, as well as rehabilitation after brain injury). This basic molecular level of brain plasticity covers numerous specific proteins (enzymes, receptors, structural proteins, etc.) participating in many coordinated and interacting signal and metabolic processes, their modulation forming a molecular basis for brain plasticity. The articles in this issue are focused on different "hot points" in the research area of biochemical mechanisms supporting neuroplasticity.

Intermittent hypercapnic hypoxia during sleep does not induce ventilatory long-term facilitation in healthy males.

PubMed

Deacon, Naomi L; McEvoy, R Doug; Stadler, Daniel L; Catcheside, Peter G

2017-09-01

Intermittent hypoxia-induced ventilatory neuroplasticity is likely important in obstructive sleep apnea pathophysiology. Although concomitant CO 2 levels and arousal state critically influence neuroplastic effects of intermittent hypoxia, no studies have investigated intermittent hypercapnic hypoxia effects during sleep in humans. Thus the purpose of this study was to investigate if intermittent hypercapnic hypoxia during sleep induces neuroplasticity (ventilatory long-term facilitation and increased chemoreflex responsiveness) in humans. Twelve healthy males were exposed to intermittent hypercapnic hypoxia (24 × 30 s episodes of 3% CO 2 and 3.0 ± 0.2% O 2 ) and intermittent medical air during sleep after 2 wk washout period in a randomized crossover study design. Minute ventilation, end-tidal CO 2 , O 2 saturation, breath timing, upper airway resistance, and genioglossal and diaphragm electromyograms were examined during 10 min of stable stage 2 sleep preceding gas exposure, during gas and intervening room air periods, and throughout 1 h of room air recovery. There were no significant differences between conditions across time to indicate long-term facilitation of ventilation, genioglossal or diaphragm electromyogram activity, and no change in ventilatory response from the first to last gas exposure to suggest any change in chemoreflex responsiveness. These findings contrast with previous intermittent hypoxia studies without intermittent hypercapnia and suggest that the more relevant gas disturbance stimulus of concomitant intermittent hypercapnia frequently occurring in sleep apnea influences acute neuroplastic effects of intermittent hypoxia. These findings highlight the need for further studies of intermittent hypercapnic hypoxia during sleep to clarify the role of ventilatory neuroplasticity in the pathophysiology of sleep apnea. NEW & NOTEWORTHY Both arousal state and concomitant CO 2 levels are known modulators of the effects of intermittent hypoxia on ventilatory neuroplasticity. This is the first study to investigate the effects of combined intermittent hypercapnic hypoxia during sleep in humans. The lack of neuroplastic effects suggests a need for further studies more closely replicating obstructive sleep apnea to determine the pathophysiological relevance of intermittent hypoxia-induced ventilatory neuroplasticity. Copyright © 2017 the American Physiological Society.

Characterization of GABA/sub A/ receptor-mediated /sup 36/chloride uptake in rat brain synaptoneurosomes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luu, M.D.; Morrow, A.L.; Paul, S.M.

1987-09-07

..gamma..-Aminobutyric acid (GABA) receptor-mediated /sup 36/chloride (/sup 36/Cl/sup -/) uptake was measured in synaptoneurosomes from rat brain. GABA and GABA agonists stimulated /sup 36/Cl/sup -/ uptake in a concentration-dependent manner with the following order of potency: Muscimol>GABA>piperidine-4-sulfonic acid (P4S)>4,5,6,7-tetrahydroisoxazolo-(5,4-c)pyridin-3-ol (THIP)=3-aminopropanesulfonic acid (3APS)>>taurine. Both P4S and 3APS behaved as partial agonists, while the GABA/sub B/ agonist, baclofen, was ineffective. The response to muscimol was inhibited by bicuculline and picrotoxin in a mixed competitive/non-competitive manner. Other inhibitors of GABA receptor-opened channels or non-neuronal anion channels such as penicillin, picrate, furosemide and disulfonic acid stilbenes also inhibited the response to muscimol. A regionalmore » variation in muscimol-stimulated /sup 36/Cl/sup -/ uptake was observed; the largest responses were observed in the cerebral cortex, cerebellum and hippocampus, moderate responses were obtained in the striatum and hypothalamus and the smallest response was observed in the pons-medulla. GABA receptor-mediated /sup 36/Cl/sup -/ uptake was also dependent on the anion present in the media. The muscinol response varied in media containing the following anions: Br/sup -/>Cl/sup -/greater than or equal toNO/sub 3//sup -/>I/sup -/greater than or equal toSCN/sup -/>>C/sub 3/H/sub 5/OO/sup -/greater than or equal toClO/sub 4//sup -/>F/sup -/, consistent with the relative anion permeability through GABA receptor-gated anion channels and the enhancement of convulsant binding to the GABA receptor-gated Cl/sup -/ channel. 43 references, 4 figures, 3 tables.« less

Reactive Oxygen Species-Mediated Loss of Synaptic Akt1 Signaling Leads to Deficient Activity-Dependent Protein Translation Early in Alzheimer's Disease

PubMed Central

Ahmad, Faraz; Singh, Kunal; Das, Debajyoti; Gowaikar, Ruturaj; Shaw, Eisha; Ramachandran, Arathy; Rupanagudi, Khader Valli; Kommaddi, Reddy Peera; Bennett, David A.

2017-01-01

Abstract Aims: Synaptic deficits are known to underlie the cognitive dysfunction seen in Alzheimer's disease (AD). Generation of reactive oxygen species (ROS) by β-amyloid has also been implicated in AD pathogenesis. However, it is unclear whether ROS contributes to synaptic dysfunction seen in AD pathogenesis and, therefore, we examined whether altered redox signaling could contribute to synaptic deficits in AD. Results: Activity dependent but not basal translation was impaired in synaptoneurosomes from 1-month old presymptomatic APPSwe/PS1ΔE9 (APP/PS1) mice, and this deficit was sustained till middle age (MA, 9–10 months). ROS generation leads to oxidative modification of Akt1 in the synapse and consequent reduction in Akt1-mechanistic target of rapamycin (mTOR) signaling, leading to deficiency in activity-dependent protein translation. Moreover, we found a similar loss of activity-dependent protein translation in synaptoneurosomes from postmortem AD brains. Innovation: Loss of activity-dependent protein translation occurs presymptomatically early in the pathogenesis of AD. This is caused by ROS-mediated loss of pAkt1, leading to reduced synaptic Akt1-mTOR signaling and is rescued by overexpression of Akt1. ROS-mediated damage is restricted to the synaptosomes, indicating selectivity. Conclusions: We demonstrate that ROS-mediated oxidative modification of Akt1 contributes to synaptic dysfunction in AD, seen as loss of activity-dependent protein translation that is essential for synaptic plasticity and maintenance. Therapeutic strategies promoting Akt1-mTOR signaling at synapses may provide novel target(s) for disease-modifying therapy in AD. Antioxid. Redox Signal. 27, 1269–1280. PMID:28264587

Structural and functional neuroplasticity in human learning of spatial routes.

PubMed

Keller, Timothy A; Just, Marcel Adam

2016-01-15

Recent findings with both animals and humans suggest that decreases in microscopic movements of water in the hippocampus reflect short-term neuroplasticity resulting from learning. Here we examine whether such neuroplastic structural changes concurrently alter the functional connectivity between hippocampus and other regions involved in learning. We collected both diffusion-weighted images and fMRI data before and after humans performed a 45min spatial route-learning task. Relative to a control group with equal practice time, there was decreased diffusivity in the posterior-dorsal dentate gyrus of the left hippocampus in the route-learning group accompanied by increased synchronization of fMRI-measured BOLD signal between this region and cortical areas, and by changes in behavioral performance. These concurrent changes characterize the multidimensionality of neuroplasticity as it enables human spatial learning. Copyright © 2015 Elsevier Inc. All rights reserved.

Cognitive tutoring induces widespread neuroplasticity and remediates brain function in children with mathematical learning disabilities.

PubMed

Iuculano, Teresa; Rosenberg-Lee, Miriam; Richardson, Jennifer; Tenison, Caitlin; Fuchs, Lynn; Supekar, Kaustubh; Menon, Vinod

2015-09-30

Competency with numbers is essential in today's society; yet, up to 20% of children exhibit moderate to severe mathematical learning disabilities (MLD). Behavioural intervention can be effective, but the neurobiological mechanisms underlying successful intervention are unknown. Here we demonstrate that eight weeks of 1:1 cognitive tutoring not only remediates poor performance in children with MLD, but also induces widespread changes in brain activity. Neuroplasticity manifests as normalization of aberrant functional responses in a distributed network of parietal, prefrontal and ventral temporal-occipital areas that support successful numerical problem solving, and is correlated with performance gains. Remarkably, machine learning algorithms show that brain activity patterns in children with MLD are significantly discriminable from neurotypical peers before, but not after, tutoring, suggesting that behavioural gains are not due to compensatory mechanisms. Our study identifies functional brain mechanisms underlying effective intervention in children with MLD and provides novel metrics for assessing response to intervention.

Brain-Derived Neurotrophic Factor, Depression, and Physical Activity: Making the Neuroplastic Connection

PubMed Central

2017-01-01

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that is vital to the survival, growth, and maintenance of neurons in key brain circuits involved in emotional and cognitive function. Convergent evidence indicates that neuroplastic mechanisms involving BDNF are deleteriously altered in major depressive disorder (MDD) and animal models of stress. Herein, clinical and preclinical evidence provided that stress-induced depressive pathology contributes to altered BDNF level and function in persons with MDD and, thereby, disruptions in neuroplasticity at the regional and circuit level. Conversely, effective therapeutics that mitigate depressive-related symptoms (e.g., antidepressants and physical activity) optimize BDNF in key brain regions, promote neuronal health and recovery of function in MDD-related circuits, and enhance pharmacotherapeutic response. A greater knowledge of the interrelationship between BDNF, depression, therapeutic mechanisms of action, and neuroplasticity is important as it necessarily precedes the derivation and deployment of more efficacious treatments. PMID:28928987

Localizationism to neuroplasticity---the evolution of metaphysical neuroscience.

PubMed

Acharya, Sourya; Shukla, Samarth; Mahajan, S N; Diwan, S K

2012-09-01

Neuroplasticity (also referred to as brain plasticity, cortical plasticity or cortical re-mapping) is the changing of neurons, organization of their networks, and their function via new experiences. The brain consists of nerve cells or neurons and glial cells which are interconnected, and learning may happen through changing of the strength of the connections between neurons, by adding or removing connections, or by adding new cells. "Plasticity" relates to learning by adding or removing connections, or adding cells. Contrary to the traditional belief of neurolocalizationism, which states that each region of brain is dedicated for a particular type of activity, neuroplasticity has struggled a long way and has created a safe niche in the neuroscientific hall of honor. Salute to the neuroplasticians for their efforts to revolutionize the doctrine of neurology for the better understanding of the remarkable powers of brain. This article is a brief attempt to fathom the mysterious and scientific ways of neuroplasticity.

Brain-Derived Neurotrophic Factor, Depression, and Physical Activity: Making the Neuroplastic Connection.

PubMed

Phillips, Cristy

2017-01-01

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that is vital to the survival, growth, and maintenance of neurons in key brain circuits involved in emotional and cognitive function. Convergent evidence indicates that neuroplastic mechanisms involving BDNF are deleteriously altered in major depressive disorder (MDD) and animal models of stress. Herein, clinical and preclinical evidence provided that stress-induced depressive pathology contributes to altered BDNF level and function in persons with MDD and, thereby, disruptions in neuroplasticity at the regional and circuit level. Conversely, effective therapeutics that mitigate depressive-related symptoms (e.g., antidepressants and physical activity) optimize BDNF in key brain regions, promote neuronal health and recovery of function in MDD-related circuits, and enhance pharmacotherapeutic response. A greater knowledge of the interrelationship between BDNF, depression, therapeutic mechanisms of action, and neuroplasticity is important as it necessarily precedes the derivation and deployment of more efficacious treatments.

Exercise-enhanced Neuroplasticity Targeting Motor and Cognitive Circuitry in Parkinson’s Disease

PubMed Central

Petzinger, G. M.; Fisher, B. E.; McEwen, S.; Beeler, J. A.; Walsh, J. P.; Jakowec, M. W.

2013-01-01

The purpose of this review is to highlight the potential role of exercise in promoting neuroplasticity and repair in Parkinson’s disease (PD). Exercise interventions in individuals with PD incorporate goal-based motor skill training in order to engage cognitive circuitry important in motor learning. Using this exercise approach, physical therapy facilitates learning through instruction and feedback (reinforcement), and encouragement to perform beyond self-perceived capability. Individuals with PD become more cognitively engaged with the practice and learning of movements and skills that were previously automatic and unconscious. Studies that have incorporated both goal-based training and aerobic exercise have supported the potential for improving both cognitive and automatic components of motor control. Utilizing animal models, basic research is beginning to reveal exercise-induced effects on neuroplasticity. Since neuroplasticity occurs at the level of circuits and synaptic connections, we examine the effects of exercise from this perspective. PMID:23769598

Lifestyle Modulators of Neuroplasticity: How Physical Activity, Mental Engagement, and Diet Promote Cognitive Health during Aging.

PubMed

Phillips, Cristy

2017-01-01

The number of the elderly across the globe will approximate 2.1 billion by 2050. Juxtaposed against this burgeoning segment of the population is evidence that nonpathological aging is associated with an increased risk for cognitive decline in a variety of domains, changes that can cause mild disability even before the onset of dementia. Given that pharmacological treatments that mitigate dementia are still outstanding, alternative therapeutic options are being investigated increasingly. The results from translational studies have shown that modifiable lifestyle factors-including physical activity, cognitive engagement, and diet-are a key strategy for maintaining brain health during aging. Indeed, a multiplicity of studies has demonstrated relationships between lifestyle factors, brain structure and function, and cognitive function in aging adults. For example, physical activity and diet modulate common neuroplasticity substrates (neurotrophic signaling, neurogenesis, inflammation, stress response, and antioxidant defense) in the brain whereas cognitive engagement enhances brain and cognitive reserve. The aims of this review are to evaluate the relationship between modifiable lifestyle factors, neuroplasticity, and optimal brain health during aging; to identify putative mechanisms that contribute positive brain aging; and to highlight future directions for scientists and clinicians. Undoubtedly, the translation of cutting-edge knowledge derived from the field of cognitive neuroscience will advance our understanding and enhance clinical treatment interventions as we endeavor to promote brain health during aging.

Lifestyle Modulators of Neuroplasticity: How Physical Activity, Mental Engagement, and Diet Promote Cognitive Health during Aging

PubMed Central

2017-01-01

The number of the elderly across the globe will approximate 2.1 billion by 2050. Juxtaposed against this burgeoning segment of the population is evidence that nonpathological aging is associated with an increased risk for cognitive decline in a variety of domains, changes that can cause mild disability even before the onset of dementia. Given that pharmacological treatments that mitigate dementia are still outstanding, alternative therapeutic options are being investigated increasingly. The results from translational studies have shown that modifiable lifestyle factors—including physical activity, cognitive engagement, and diet—are a key strategy for maintaining brain health during aging. Indeed, a multiplicity of studies has demonstrated relationships between lifestyle factors, brain structure and function, and cognitive function in aging adults. For example, physical activity and diet modulate common neuroplasticity substrates (neurotrophic signaling, neurogenesis, inflammation, stress response, and antioxidant defense) in the brain whereas cognitive engagement enhances brain and cognitive reserve. The aims of this review are to evaluate the relationship between modifiable lifestyle factors, neuroplasticity, and optimal brain health during aging; to identify putative mechanisms that contribute positive brain aging; and to highlight future directions for scientists and clinicians. Undoubtedly, the translation of cutting-edge knowledge derived from the field of cognitive neuroscience will advance our understanding and enhance clinical treatment interventions as we endeavor to promote brain health during aging. PMID:28695017

Enhancing Neuroplasticity to Augment Cognitive Remediation in Schizophrenia.

PubMed

Jahshan, Carol; Rassovsky, Yuri; Green, Michael F

2017-01-01

There is a burgeoning need for innovative treatment strategies to improve the cognitive deficits in schizophrenia. Cognitive remediation (CR) is effective at the group level, but the variability in treatment response is large. Given that CR may depend on intact neuroplasticity to produce cognitive gains, it is reasonable to combine it with strategies that harness patients' neuroplastic potential. In this review, we discuss two non-pharmacological approaches that can enhance neuroplasticity and possibly augment the effects of CR in schizophrenia: physical exercise and transcranial direct current stimulation (tDCS). Substantial body of evidence supports the beneficial effect of physical exercise on cognition, and a handful of studies in schizophrenia have shown that physical exercise in conjunction with CR has a larger impact on cognition than CR alone. Physical exercise is thought to stimulate neuroplasticity through the regulation of central growth factors, and current evidence points to brain-derived neurotrophic factor as the potential underlying mechanism through which physical exercise might enhance the effectiveness of CR. tDCS has emerged as a potential tool for cognitive enhancement and seems to affect the cellular mechanisms involved in long-term potentiation (LTP). A few reports have demonstrated the feasibility of integrating tDCS with CR in schizophrenia, but there are insufficient data to determine if this multimodal approach leads to incremental performance gain in patients. Larger randomized controlled trials are necessary to understand the mechanisms of the combined tDCS-CR intervention. Future research should take advantage of new developments in neuroplasticity paradigms to examine the effects of these interventions on LTP.

Effect of Neuroscience-Based Cognitive Skill Training on Growth of Cognitive Deficits Associated with Learning Disabilities in Children Grades 2-4

ERIC Educational Resources Information Center

Avtzon, Sarah Abitbol

2012-01-01

Working memory, executive functions, and cognitive processes associated with specific academic areas, are empirically identified as being the core underlying cognitive deficits in students with specific learning disabilities. Using Hebb's theory of neuroplasticity and the principle of automaticity as theoretical bases, this experimental study…

Repeated restraint stress-induced atrophy of glutamatergic pyramidal neurons and decreases in glutamatergic efflux in the rat amygdala are prevented by the antidepressant agomelatine.

PubMed

Grillo, C A; Risher, M; Macht, V A; Bumgardner, A L; Hang, A; Gabriel, C; Mocaër, E; Piroli, G G; Fadel, J R; Reagan, L P

2015-01-22

Major depressive illness is among the most prevalent neuropsychiatric disorders and is associated with neuroplasticity deficits in limbic structures such as the amygdala. Since exposure to stressful life events is proposed to contribute to depressive illness, our recent studies examined the effects of stress on amygdalar neuroplasticity. These studies determined that repeated stress elicits deficits in glutamatergic activity in the amygdala, neuroplasticity deficits that can be prevented by some but not all antidepressants. In view of these observations, the goal of the current study was to determine the effects of repeated restraint stress (RRS) on the dendritic architecture of pyramidal neurons in the rat basolateral nucleus of the amygdala (CBL), as well as glutamate efflux in the CBL and central nucleus of the amygdala (CMX) via in vivo microdialysis. We also examined the ability of the antidepressant agomelatine to prevent RRS-induced neuroplasticity deficits. Compared with control rats, rats subjected to RRS exhibited atrophy of CBL pyramidal neurons, including decreases in total dendritic length, branch points, and dendritic complexity index. In addition, glutamate efflux was significantly reduced in the CMX of rats subjected to RRS, thereby identifying a potential neurochemical consequence of stress-induced dendritic atrophy of CBL pyramidal neurons. Lastly, an acute stress challenge increased corticosterone (CORT) levels in the CBL, suggesting that stress-induced increases in CORT levels may contribute to the neuroanatomical and neurochemical effects of RRS in the CBL. Importantly, these RRS-induced changes were prevented by daily agomelatine administration. These results demonstrate that the neuroanatomical and neurochemical properties of glutamatergic neurons in the rat amygdala are adversely affected by repeated stress and suggest that the therapeutic effects of agomelatine may include protection of structural and neurochemical plasticity in limbic structures like the amygdala. Published by Elsevier Ltd.

Similarities and differences in neuroplasticity mechanisms between brain gliomas and nonlesional epilepsy.

PubMed

Bourdillon, Pierre; Apra, Caroline; Guénot, Marc; Duffau, Hugues

2017-12-01

To analyze the conceptual and practical implications of a hodotopic approach in neurosurgery, and to compare the similarities and the differences in neuroplasticity mechanisms between low-grade gliomas and nonlesional epilepsy. We review the recent data about the hodotopic organization of the brain connectome, alongside the organization of epileptic networks, and analyze how these two structures interact, suggesting therapeutic prospects. Then we focus on the mechanisms of neuroplasticity involved in glioma natural course and after glioma surgery. Comparing these mechanisms with those in action in an epileptic brain highlights their differences, but more importantly, gives an original perspective to the consequences of surgery on an epileptic brain and what could be expected after pathologic white matter removal. The organization of the brain connectome and the neuroplasticity is the same in all humans, but different pathologic mechanisms are involved, and specific therapeutic approaches have been developed in epilepsy and glioma surgery. We demonstrate that the "connectome" point of view can enrich epilepsy care. We also underscore how theoretical and practical tools commonly used in epilepsy investigations, such as invasive electroencephalography, can be of great help in awake surgery in general. Putting together advances in understanding of connectomics and neuroplasticity, leads to significant conceptual improvements in epilepsy surgery. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

α-Tocopherol and Hippocampal Neural Plasticity in Physiological and Pathological Conditions

PubMed Central

Ambrogini, Patrizia; Betti, Michele; Galati, Claudia; Di Palma, Michael; Lattanzi, Davide; Savelli, David; Galli, Francesco; Cuppini, Riccardo; Minelli, Andrea

2016-01-01

Neuroplasticity is an “umbrella term” referring to the complex, multifaceted physiological processes that mediate the ongoing structural and functional modifications occurring, at various time- and size-scales, in the ever-changing immature and adult brain, and that represent the basis for fundamental neurocognitive behavioral functions; in addition, maladaptive neuroplasticity plays a role in the pathophysiology of neuropsychiatric dysfunctions. Experiential cues and several endogenous and exogenous factors can regulate neuroplasticity; among these, vitamin E, and in particular α-tocopherol (α-T), the isoform with highest bioactivity, exerts potent effects on many plasticity-related events in both the physiological and pathological brain. In this review, the role of vitamin E/α-T in regulating diverse aspects of neuroplasticity is analyzed and discussed, focusing on the hippocampus, a brain structure that remains highly plastic throughout the lifespan and is involved in cognitive functions. Vitamin E-mediated influences on hippocampal synaptic plasticity and related cognitive behavior, on post-natal development and adult hippocampal neurogenesis, as well as on cellular and molecular disruptions in kainate-induced temporal seizures are described. Besides underscoring the relevance of its antioxidant properties, non-antioxidant functions of vitamin E/α-T, mainly involving regulation of cell signaling molecules and their target proteins, have been highlighted to help interpret the possible mechanisms underlying the effects on neuroplasticity. PMID:27983697

The effect of manual therapy and neuroplasticity education on chronic low back pain: a randomized clinical trial.

PubMed

Louw, Adriaan; Farrell, Kevin; Landers, Merrill; Barclay, Martin; Goodman, Elise; Gillund, Jordan; McCaffrey, Sara; Timmerman, Laura

2017-12-01

To determine if a neuroplasticity educational explanation for a manual therapy technique will produce a different outcome compared to a traditional mechanical explanation. Sixty-two patients with chronic low back pain (CLBP) were recruited for the study. Following consent, demographic data were obtained as well as pain ratings for low back pain (LBP) and leg pain (Numeric Pain Rating Scale), disability (Oswestry Disability Index), fear-avoidance (Fear-Avoidance-Beliefs Questionnaire), forward flexion (fingertips-to-floor), and straight leg raise (SLR) (inclinometer). Patients were then randomly allocated to receive one of two explanations (neuroplasticity or mechanical), a manual therapy technique to their lumbar spine, followed by post-intervention measurements of LBP, leg pain, forward flexion, and SLR. Sixty-two patients (female 35 [56.5%]), with a mean age of 60.1 years and mean duration of 9.26 years of CLBP participated in the study. There were no statistically significant interactions for LBP ( p  = .325), leg pain ( p  = .172), and trunk flexion ( p  = .818) between the groups, but SLR showed a significant difference in favor of the neuroplasticity explanation ( p  = .041). Additionally, the neuroplasticity group were 7.2 times (95% confidence interval = 1.8-28.6) more likely to improve beyond the MDC on the SLR than participants in the mechanical group. The results of this study show that a neuroplasticity explanation, compared to a traditional biomechanical explanation, resulted in a measureable difference in SLR in patients with CLBP when receiving manual therapy. Future studies need to explore if the increase in SLR correlated to changes in cortical maps of the low back.

Dairy fat blend improves brain DHA and neuroplasticity and regulates corticosterone in mice.

PubMed

Dinel, A L; Rey, C; Bonhomme, C; Le Ruyet, P; Joffre, C; Layé, S

2016-06-01

Mimicking the breast milk lipid composition appears to be necessary for infant formula to cover the brain's needs in n-3 PUFA. In this study, we evaluated the impact of partial replacement of vegetable oil (VL) in infant formula by dairy fat (DL) on docosahexaenoic acid (DHA) brain level, neuroplasticity and corticosterone in mice. Mice were fed with balanced VL or balanced DL diets enriched or not in DHA and arachidonic acid (ARA) from the first day of gestation. Brain DHA level, microglia number, neurogenesis, corticosterone and glucocorticoid receptor expression were measured in the offsprings. DL diet increased DHA and neuroplasticity in the brain of mice at postnatal day (PND) 14 and at adulthood compared to VL. At PND14, ARA and DHA supplementation increased DHA in VL but not in DL mice brain. Importantly, DHA and ARA supplementation further improved neurogenesis and decreased corticosterone level in DL mice at adulthood. In conclusion, dairy lipids improve brain DHA level and neuroplasticity. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Depression and neuroplasticity. Interaction of nervous, endocrine and immune systems].

PubMed

Cassano, Paola; Argibay, Pablo

2010-01-01

Clinical depression is a physical and psychic disease that has neuropathological basis, although the clear understanding of its ethiopathology is still missing. There is evidence of a genetic component in depression, however, the participation of environment is crucial. Stress plays an essential role in the onset of depression. The interaction and the response of the endocrine system with the immune and nervous system are altered in depression. The observation of the effect of antidepressants on monoaminergic transmitters leads to the hypothesis of monoamines. However this hypothesis cannot explain many of the mechanisms involved in the action of antidepressants. The new hypothesis proposed to explain the action of antidepressant is the neuro-plasticity hypothesis. This hypothesis suggests that the effects of antidepressants on nervous, immune and endocrine systems are able to induce neuroadaptative changes in the brain. The neuroplasticity have been described as the ability of the brain to reorganize itself and form new neuronal connections throughout life. It is proposed that antidepressants influence neuroplasticity inducing improvements in the symptoms of this illness.

Time of Day Does Not Modulate Improvements in Motor Performance following a Repetitive Ballistic Motor Training Task

PubMed Central

Sale, Martin V.; Ridding, Michael C.; Nordstrom, Michael A.

2013-01-01

Repetitive performance of a task can result in learning. The neural mechanisms underpinning such use-dependent plasticity are influenced by several neuromodulators. Variations in neuromodulator levels may contribute to the variability in performance outcomes following training. Circulating levels of the neuromodulator cortisol change throughout the day. High cortisol levels inhibit neuroplasticity induced with a transcranial magnetic stimulation (TMS) paradigm that has similarities to use-dependent plasticity. The present study investigated whether performance changes following a motor training task are modulated by time of day and/or changes in endogenous cortisol levels. Motor training involving 30 minutes of repeated maximum left thumb abduction was undertaken by twenty-two participants twice, once in the morning (8 AM) and once in the evening (8 PM) on separate occasions. Saliva was assayed for cortisol concentration. Motor performance, quantified by measuring maximum left thumb abduction acceleration, significantly increased by 28% following training. Neuroplastic changes in corticomotor excitability of abductor pollicis brevis, quantified with TMS, increased significantly by 23% following training. Training-related motor performance improvements and neuroplasticity were unaffected by time of day and salivary cortisol concentration. Although similar neural elements and processes contribute to motor learning, training-induced neuroplasticity, and TMS-induced neuroplasticity, our findings suggest that the influence of time of day and cortisol differs for these three interventions. PMID:23577271

Motor skill changes and neurophysiologic adaptation to recovery-oriented virtual rehabilitation of hand function in a person with subacute stroke: a case study

PubMed Central

Fluet, Gerard G.; Patel, Jigna; Qiu, Qinyin; Yarossi, Matthew; Massood, Supriya; Adamovich, Sergei V.; Tunik, Eugene; Merians, Alma S.

2016-01-01

Purpose The complexity of upper extremity (UE) behavior requires recovery of near normal neuromuscular function to minimize residual disability following a stroke. This requirement places a premium on spontaneous recovery and neuroplastic adaptation to rehabilitation by the lesioned hemisphere. Motor skill learning is frequently cited as a requirement for neuroplasticity. Studies examining the links between training, motor learning, neuroplasticity, and improvements in hand motor function are indicated. Methods This case study describes a patient with slow recovering hand and finger movement (Total Upper Extremity Fugl–Meyer examination score = 25/66, Wrist and Hand items = 2/24 on poststroke day 37) following a stroke. The patient received an intensive eight-session intervention utilizing simulated activities that focused on the recovery of finger extension, finger individuation, and pinch-grasp force modulation. Results Over the eight sessions, the patient demonstrated improvements on untrained transfer tasks, which suggest that motor learning had occurred, as well a dramatic increase in hand function and corresponding expansion of the cortical motor map area representing several key muscles of the paretic hand. Recovery of hand function and motor map expansion continued after discharge through the three-month retention testing. Conclusion This case study describes a neuroplasticity based intervention for UE hemiparesis and a model for examining the relationship between training, motor skill acquisition, neuroplasticity, and motor function changes. PMID:27669997

Dynamic Brains and the Changing Rules of Neuroplasticity: Implications for Learning and Recovery

PubMed Central

Voss, Patrice; Thomas, Maryse E.; Cisneros-Franco, J. Miguel; de Villers-Sidani, Étienne

2017-01-01

A growing number of research publications have illustrated the remarkable ability of the brain to reorganize itself in response to various sensory experiences. A traditional view of this plastic nature of the brain is that it is predominantly limited to short epochs during early development. Although examples showing that neuroplasticity exists outside of these finite time-windows have existed for some time, it is only recently that we have started to develop a fuller understanding of the different regulators that modulate and underlie plasticity. In this article, we will provide several lines of evidence indicating that mechanisms of neuroplasticity are extremely variable across individuals and throughout the lifetime. This variability is attributable to several factors including inhibitory network function, neuromodulator systems, age, sex, brain disease, and psychological traits. We will also provide evidence of how neuroplasticity can be manipulated in both the healthy and diseased brain, including recent data in both young and aged rats demonstrating how plasticity within auditory cortex can be manipulated pharmacologically and by varying the quality of sensory inputs. We propose that a better understanding of the individual differences that exist within the various mechanisms that govern experience-dependent neuroplasticity will improve our ability to harness brain plasticity for the development of personalized translational strategies for learning and recovery following brain injury or disease. PMID:29085312

Neuroplastic Changes Induced by Cognitive Rehabilitation in Traumatic Brain Injury: A Review.

PubMed

Galetto, Valentina; Sacco, Katiuscia

2017-09-01

Cognitive deficits are among the most disabling consequences of traumatic brain injury (TBI), leading to long-term outcomes and interfering with the individual's recovery. One of the most effective ways to reduce the impact of cognitive disturbance in everyday life is cognitive rehabilitation, which is based on the principles of brain neuroplasticity and restoration. Although there are many studies in the literature focusing on the effectiveness of cognitive interventions in reducing cognitive deficits following TBI, only a few of them focus on neural modifications induced by cognitive treatment. The use of neuroimaging or neurophysiological measures to evaluate brain changes induced by cognitive rehabilitation may have relevant clinical implications, since they could add individualized elements to cognitive assessment. Nevertheless, there are no review studies in the literature investigating neuroplastic changes induced by cognitive training in TBI individuals. Due to lack of data, the goal of this article is to review what is currently known on the cerebral modifications following rehabilitation programs in chronic TBI. Studies investigating both the functional and structural neural modifications induced by cognitive training in TBI subjects were identified from the results of database searches. Forty-five published articles were initially selected. Of these, 34 were excluded because they did not meet the inclusion criteria. Eleven studies were found that focused solely on the functional and neurophysiological changes induced by cognitive rehabilitation. Outcomes showed that cerebral activation may be significantly modified by cognitive rehabilitation, in spite of the severity of the injury.

The Various Forms of Neuroplasticity: Biological Bases of Learning and Teaching

ERIC Educational Resources Information Center

Tovar-Moll, Fernanda; Lent, Roberto

2016-01-01

Education is a socially structured form of learning. It involves the brains of different players--students, teachers, family members, and others--in permanent interaction. The biological set of mechanisms by which these brains receive, encode, store, and retrieve mutually exchanged information is called "neuroplasticity". This is the…

Death receptor Fas (CD95) signaling in the central nervous system: tuning neuroplasticity?

PubMed

Reich, Arno; Spering, Christopher; Schulz, Jörg B

2008-09-01

For over a decade, neuroscientific research has focused on processes of apoptosis and its contribution to the pathophysiology of neurological diseases. In the central nervous system, the degree of intrinsic mitochondrial-mediated apoptotic signaling expresses a cell's individual metabolic stress, whereas activation of the extrinsic death receptor-induced cascade is regarded as a sign of imbalanced cellular networks. Under physiological conditions, most neurons possess death receptors without being sensitive to receptor-mediated apoptosis. This paradox raises two questions: what is the evolutionary advantage of expressing potentially harmful proteins? How is their signaling controlled? This review summarizes the functional relevance of FasL-Fas signaling--a quintessential death ligand/receptor system--in different neurological disease models ranging from traumatic, inflammatory and ischemic to neurodegenerative processes. Furthermore, it outlines alternative non-apoptotic Fas signaling, shedding new light on its neuroplastic capacity. Finally, receptor-proximal regulatory proteins are introduced and identified as potential protagonists of disease-modifying neurological therapies.

Cognitive tutoring induces widespread neuroplasticity and remediates brain function in children with mathematical learning disabilities

PubMed Central

Iuculano, Teresa; Rosenberg-Lee, Miriam; Richardson, Jennifer; Tenison, Caitlin; Fuchs, Lynn; Supekar, Kaustubh; Menon, Vinod

2015-01-01

Competency with numbers is essential in today's society; yet, up to 20% of children exhibit moderate to severe mathematical learning disabilities (MLD). Behavioural intervention can be effective, but the neurobiological mechanisms underlying successful intervention are unknown. Here we demonstrate that eight weeks of 1:1 cognitive tutoring not only remediates poor performance in children with MLD, but also induces widespread changes in brain activity. Neuroplasticity manifests as normalization of aberrant functional responses in a distributed network of parietal, prefrontal and ventral temporal–occipital areas that support successful numerical problem solving, and is correlated with performance gains. Remarkably, machine learning algorithms show that brain activity patterns in children with MLD are significantly discriminable from neurotypical peers before, but not after, tutoring, suggesting that behavioural gains are not due to compensatory mechanisms. Our study identifies functional brain mechanisms underlying effective intervention in children with MLD and provides novel metrics for assessing response to intervention. PMID:26419418

Facilitating neurorehabilitation through principles of engagement.

PubMed

Danzl, Megan M; Etter, Nicole M; Andreatta, Richard D; Kitzman, Patrick H

2012-01-01

A primary goal of neurorehabilitation is to guide recovery of functional skills after injury through evidence-based interventions that operate to manipulate the sensorimotor environment of the client. While choice of intervention is an important decision for clinicians, we contend it is only one part of producing optimal activity-dependent neuroplastic changes. A key variable in the rehabilitation equation is engagement. Applying principles of engagement may yield greater neuroplastic changes and functional outcomes for clients. We review the principles of neuroplasticity and engagement and their potential linkage through concepts of attention and motivation and strategies such as mental practice and enriched environments. Clinical applications and challenges for enhancing engagement during rehabilitation are presented. Engagement strategies, such as building trust and rapport, motivational interviewing, enhancing the client education process, and interventions that empower clients, are reviewed. Well-controlled research is needed to test our theoretical framework and suggested outcomes. Clinicians may enhance engagement by investing time and energy in the growth and development of the therapeutic relationship with clients, as this is paramount to maintaining clients' investment in continuing therapy and also may act as a driver of neuroplastic changes.

Motherhood and infant contact regulate neuroplasticity in the serotonergic midbrain dorsal raphe.

PubMed

Holschbach, M Allie; Lonstein, Joseph S

2017-02-01

The adult brain shows remarkable neuroplasticity in response to hormones and the socioemotional modifications that they influence. In females with reproductive and maternal experience, this neuroplasticity includes the birth and death of cells in several forebrain regions involved in maternal caregiving and postpartum affective state. Such plasticity in midbrain sites critical for these behavioral and emotional processes has never been examined, though. By visualizing bromodeoxyuridine (BrdU) to label mitotic cells, NeuroD for neuronal precursors, and TUNEL to identify dying cells, we found that the midbrain dorsal raphe nucleus (DR, the source of most ascending serotoninergic projections) exhibited significant neuroplasticity in response to motherhood. Specifically, BrdU analyses revealed that DR newborn cell survival (but not proliferation) was regulated by reproductive state, such that cells born early postpartum were less likely to survive 12 days to reach the late postpartum period compared to cells born during late pregnancy that survived 12 days to reach the early postpartum period. Many of the surviving cells in the DR were NeuN immunoreactive, suggesting a neuronal phenotype. Consistent with these findings, late postpartum rats had fewer NeuroD-immunoreactive DR cells than early postpartum rats. Maternal experience contributed to the late postpartum reduction in DR newborn cell survival because removing the litter at parturition increased cell survival as well as reduced cell death. Unlike cytogenesis in the maternal hippocampus, which is reduced by circulating glucocorticoids, DR newborn cell survival was unaffected by postpartum adrenalectomy. These effects of reproductive state and motherhood on DR plasticity were associated with concurrent changes in DR levels of serotonin's precursor, 5-HTP, and its metabolite, 5-HIAA. Our results demonstrate for the first time that cytogenesis occurs in the midbrain DR of any adult mammal, that DR plasticity is influenced by female reproductive state and maternal experience, and that this plasticity is accompanied by changes in DR serotonergic function. Because serotonin is critical for postpartum caregiving behaviors and maternal affective state, plasticity in the DR may contribute to the neurochemical changes necessary for successful motherhood. Copyright © 2016 Elsevier Ltd. All rights reserved.

Physical Activity Modulates Common Neuroplasticity Substrates in Major Depressive and Bipolar Disorder.

PubMed

Phillips, Cristy

2017-01-01

Mood disorders (MDs) are chronic, recurrent mental diseases that affect millions of individuals worldwide. Although the biogenic amine model has provided some clinical utility, a need remains to better understand the interrelated mechanisms that contribute to neuroplasticity deficits in MDs and the means by which various therapeutics mitigate them. Of those therapeutics being investigated, physical activity (PA) has shown clear and consistent promise. Accordingly, the aims of this review are to (1) explicate key modulators, processes, and interactions that impinge upon multiple susceptibility points to effectuate neuroplasticity deficits in MDs; (2) explore the putative mechanisms by which PA mitigates these features; (3) review protocols used to induce the positive effects of PA in MDs; and (4) highlight implications for clinicians and researchers.

Neurometaplasticity: Glucoallostasis control of plasticity of the neural networks of error commission, detection, and correction modulates neuroplasticity to influence task precision

NASA Astrophysics Data System (ADS)

Welcome, Menizibeya O.; Dane, Şenol; Mastorakis, Nikos E.; Pereverzev, Vladimir A.

2017-12-01

The term "metaplasticity" is a recent one, which means plasticity of synaptic plasticity. Correspondingly, neurometaplasticity simply means plasticity of neuroplasticity, indicating that a previous plastic event determines the current plasticity of neurons. Emerging studies suggest that neurometaplasticity underlie many neural activities and neurobehavioral disorders. In our previous work, we indicated that glucoallostasis is essential for the control of plasticity of the neural network that control error commission, detection and correction. Here we review recent works, which suggest that task precision depends on the modulatory effects of neuroplasticity on the neural networks of error commission, detection, and correction. Furthermore, we discuss neurometaplasticity and its role in error commission, detection, and correction.

Neural basis of major depressive disorder: Beyond monoamine hypothesis.

PubMed

Boku, Shuken; Nakagawa, Shin; Toda, Hiroyuki; Hishimoto, Akitoyo

2018-01-01

The monoamine hypothesis has been accepted as the most common hypothesis of major depressive disorder (MDD) for a long period because of its simplicity and understandability. Actually, most currently used antidepressants have been considered to act based on the monoamine hypothesis. However, an important problem of the monoamine hypothesis has been pointed out as follows: it fails to explain the latency of response to antidepressants. In addition, many patients with MDD have remained refractory to currently used antidepressants. Therefore, monoamine-alternate hypotheses are required to explain the latency of response to antidepressants. Such hypotheses have been expected to contribute to identifying hopeful new therapeutic targets for MDD. Past studies have revealed that the volume of the hippocampus is decreased in patients with MDD, which is likely caused by the failure of the hypothalamic-pituitary-adrenal axis and following elevation of glucocorticoids. Two hypotheses have been proposed to explain the volume of the hippocampus: (i) the neuroplasticity hypothesis; and (ii) the neurogenesis hypothesis. The neuroplasticity hypothesis explains how the hippocampal volume is decreased by the morphological changes of hippocampal neurons, such as the shortening length of dendrites and the decreased number and density of spines. The neurogenesis hypothesis explains how the hippocampal volume is decreased by the decrease of neurogenesis in the hippocampal dentate gyrus. These hypotheses are able to explain the latency of response to antidepressants. In this review, we first overview how the neuroplasticity and neurogenesis hypotheses have been developed. We then describe the details of these hypotheses. © 2017 The Authors. Psychiatry and Clinical Neurosciences © 2017 Japanese Society of Psychiatry and Neurology.

Environmental Enrichment and Social Isolation Mediate Neuroplasticity of Medium Spiny Neurons through the GSK3 Pathway.

PubMed

Scala, Federico; Nenov, Miroslav N; Crofton, Elizabeth J; Singh, Aditya K; Folorunso, Oluwarotimi; Zhang, Yafang; Chesson, Brent C; Wildburger, Norelle C; James, Thomas F; Alshammari, Musaad A; Alshammari, Tahani K; Elfrink, Hannah; Grassi, Claudio; Kasper, James M; Smith, Ashley E; Hommel, Jonathan D; Lichti, Cheryl F; Rudra, Jai S; D'Ascenzo, Marcello; Green, Thomas A; Laezza, Fernanda

2018-04-10

Resilience and vulnerability to neuropsychiatric disorders are linked to molecular changes underlying excitability that are still poorly understood. Here, we identify glycogen-synthase kinase 3β (GSK3β) and voltage-gated Na + channel Nav1.6 as regulators of neuroplasticity induced by environmentally enriched (EC) or isolated (IC) conditions-models for resilience and vulnerability. Transcriptomic studies in the nucleus accumbens from EC and IC rats predicted low levels of GSK3β and SCN8A mRNA as a protective phenotype associated with reduced excitability in medium spiny neurons (MSNs). In vivo genetic manipulations demonstrate that GSK3β and Nav1.6 are molecular determinants of MSN excitability and that silencing of GSK3β prevents maladaptive plasticity of IC MSNs. In vitro studies reveal direct interaction of GSK3β with Nav1.6 and phosphorylation at Nav1.6 T1936 by GSK3β. A GSK3β-Nav1.6 T1936 competing peptide reduces MSNs excitability in IC, but not EC rats. These results identify GSK3β regulation of Nav1.6 as a biosignature of MSNs maladaptive plasticity. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Probing the Role of HDACs and Mechanisms of Chromatin-Mediated Neuroplasticity

PubMed Central

Haggarty, Stephen J.; Tsai, Li-Huei

2011-01-01

Advancing our understanding of neuroplasticity and the development of novel therapeutics based upon this knowledge is critical in order to improve the treatment and prevention of a myriad of nervous system disorders. Epigenetic mechanisms of neuroplasticity involve the post-translational modification of chromatin and the recruitment or loss of macromolecular complexes that control neuronal activity-dependent gene expression. While over a century after Ramón y Cajal first described nuclear subcompartments and foci that we now know correspond to sites of active transcription with acetylated histones that are under epigenetic control, the rate and extent to which epigenetic processes act in a dynamic and combinatorial fashion to shape experience-dependent phenotypic and behavioral plasticity in response to various types of neuronal stimuli over a range of time scales is only now coming into focus. With growing recognition that a subset of human diseases involving cognitive dysfunction can be classified as ‘chromatinopathies’, in which aberrant chromatin-mediated neuroplasticity plays a causal role in the underlying disease pathophysiology, understanding the molecular nature of epigenetic mechanisms in the nervous system may provide important new avenues for the development of novel therapeutics. In this review, we discuss the chemistry and neurobiology of the histone deacetylase (HDAC) family of chromatin-modifying enzymes, outline the role of HDACs in the epigenetic control of neuronal function, and discuss the potential relevance of these epigenetic mechanisms to the development of therapeutics aiming to enhance memory and neuroplasticity. Finally, open questions, challenges, and critical needs for the field of ‘neuroepigenetics’ in the years to come will be summarized. PMID:21545841

The Effect of Aerobic Exercise on Neuroplasticity within the Motor Cortex following Stroke

PubMed Central

Murdoch, Kate; Buckley, Jonathan D.; McDonnell, Michelle N.

2016-01-01

Background Aerobic exercise is associated with enhanced plasticity in the motor cortex of healthy individuals, but the effect of aerobic exercise on neuroplasticity following a stroke is unknown. Objective The aim of this study was to compare corticomotoneuronal excitability and neuroplasticity in the upper limb cortical representation following a single session of low intensity lower limb cycling, or a rest control condition. Methods We recruited chronic stroke survivors to take part in three experimental conditions in a randomised, cross-over design. Corticomotoneuronal excitability was examined using transcranial magnetic stimulation to elicit motor evoked potentials in the affected first dorsal interosseus muscle. Following baseline measures, participants either cycled on a stationary bike at a low exercise intensity for 30 minutes, or remained resting in a seated position for 30 minutes. Neuroplasticity within the motor cortex was then examined using an intermittent theta burst stimulation (iTBS) paradigm. During the third experimental condition, participants cycled for the 30 minutes but did not receive any iTBS. Results Twelve participants completed the study. We found no significant effect of aerobic exercise on corticomotoneuronal excitability when compared to the no exercise condition (P > 0.05 for all group and time comparisons). The use of iTBS did not induce a neuroplastic-like response in the motor cortex with or without the addition of aerobic exercise. Conclusions Our results suggest that following a stroke, the brain may be less responsive to non-invasive brain stimulation paradigms that aim to induce short-term reorganisation, and aerobic exercise was unable to induce or improve this response. PMID:27018862

High-intensity Aerobic Exercise Blocks the Facilitation of iTBS-induced Plasticity in the Human Motor Cortex.

PubMed

Smith, Ashleigh E; Goldsworthy, Mitchell R; Wood, Fiona M; Olds, Timothy S; Garside, Tessa; Ridding, Michael C

2018-03-01

Acute exercise studies using transcranial magnetic stimulation (TMS) can provide important insights into the mechanisms underpinning the positive relationship between regular engagement in physical activity and cortical neuroplasticity. Emerging evidence indicates that a single session of aerobic exercise can promote the response to an experimentally induced suppressive neuroplasticity paradigm; however, little is known about the neuroplasticity response to facilitatory paradigms, including intermittent theta burst stimulation (iTBS). To more fully characterize the effects of exercise on brain plasticity we investigated if a single 30 min bout of high-intensity cycling (80% predicted heart rate reserve) modulated the response to an iTBS paradigm compared to rest. In 18 participants (9 females; 25.5 ± 5.0 years, range: 18-35 years) iTBS was applied using standard repetitive transcranial magnetic stimulation techniques immediately following exercise or 30 min of rest. Motor evoked potentials (MEPs) were recorded from the right first dorsal interosseous muscle at baseline, after the exercise/rest period but before iTBS, and at 5 time points following iTBS (0, 5, 10, 20 and 30 min). Contrary to our hypothesis, MEPs were suppressed following iTBS after a single 30 min bout of lower limb aerobic exercise compared to rest. These results indicate that acute aerobic exercise may not always enhance the response to an experimentally induced neuroplasticity paradigm. Further investigation of the factors that influence the relationship between exercise and neuroplasticity is warranted. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Exercise-induced neuroplasticity in human Parkinson's disease: What is the evidence telling us?

PubMed

Hirsch, Mark A; Iyer, Sanjay S; Sanjak, Mohammed

2016-01-01

While animal models of exercise and PD have pushed the field forward, few studies have addressed exercise-induced neuroplasticity in human PD. As a first step toward promoting greater international collaboration on exercise-induced neuroplasticity in human PD, we present data on 8 human PD studies (published between 2008 and 2015) with 144 adults with PD of varying disease severity (Hoehn and Yahr stage 1 to stage 3), using various experimental (e.g., randomized controlled trial) and quasi-experimental designs on the effects of cognitive and physical activity on brain structure or function in PD. We focus on plasticity mechanisms of intervention-induced increases in maximal corticomotor excitability, exercise-induced changes in voxel-based gray matter volume changes and increases in exercise-induced serum levels of brain derived neurotrophic factor (BDNF). Finally, we provide a future perspective for promoting international, collaborative research on exercise-induced neuroplasticity in human PD. An emerging body of evidence suggests exercise triggers several plasticity related events in the human PD brain including corticomotor excitation, increases and decreases in gray matter volume and changes in BDNF levels. Copyright © 2015 Elsevier Ltd. All rights reserved.

Physical Activity Modulates Common Neuroplasticity Substrates in Major Depressive and Bipolar Disorder

PubMed Central

2017-01-01

Mood disorders (MDs) are chronic, recurrent mental diseases that affect millions of individuals worldwide. Although the biogenic amine model has provided some clinical utility, a need remains to better understand the interrelated mechanisms that contribute to neuroplasticity deficits in MDs and the means by which various therapeutics mitigate them. Of those therapeutics being investigated, physical activity (PA) has shown clear and consistent promise. Accordingly, the aims of this review are to (1) explicate key modulators, processes, and interactions that impinge upon multiple susceptibility points to effectuate neuroplasticity deficits in MDs; (2) explore the putative mechanisms by which PA mitigates these features; (3) review protocols used to induce the positive effects of PA in MDs; and (4) highlight implications for clinicians and researchers. PMID:28529805

Motor learning in a complex balance task and associated neuroplasticity: a comparison between endurance athletes and nonathletes.

PubMed

Seidel, Oliver; Carius, Daniel; Kenville, Rouven; Ragert, Patrick

2017-09-01

Studies suggested that motor expertise is associated with functional and structural brain alterations, which positively affect sensorimotor performance and learning capabilities. The purpose of the present study was to unravel differences in motor skill learning and associated functional neuroplasticity between endurance athletes (EA) and nonathletes (NA). For this purpose, participants had to perform a multimodal balance task (MBT) training on 2 sessions, which were separated by 1 wk. Before and after MBT training, a static balance task (SBT) had to be performed. MBT-induced functional neuroplasticity and neuromuscular alterations were assessed by means of functional near-infrared spectroscopy (fNIRS) and electromyography (EMG) during SBT performance. We hypothesized that EA would showed superior initial SBT performance and stronger MBT-induced improvements in SBT learning rates compared with NA. On a cortical level, we hypothesized that MBT training would lead to differential learning-dependent functional changes in motor-related brain regions [such as primary motor cortex (M1)] during SBT performance. In fact, EA showed superior initial SBT performance, whereas learning rates did not differ between groups. On a cortical level, fNIRS recordings (time × group interaction) revealed a stronger MBT-induced decrease in left M1 and inferior parietal lobe (IPL) for deoxygenated hemoglobin in EA. Even more interesting, learning rates were correlated with fNIRS changes in right M1/IPL. On the basis of these findings, we provide novel evidence for superior MBT training-induced functional neuroplasticity in highly trained athletes. Future studies should investigate these effects in different sports disciplines to strengthen previous work on experience-dependent neuroplasticity. NEW & NOTEWORTHY Motor expertise is associated with functional/structural brain plasticity. How such neuroplastic reorganization translates into altered motor learning processes remains elusive. We investigated endurance athletes (EA) and nonathletes (NA) in a multimodal balance task (MBT). EA showed superior static balance performance (SBT), whereas MBT-induced SBT improvements did not differ between groups. Functional near-infrared spectroscopy recordings revealed a differential MBT training-induced decrease of deoxygenated hemoglobin in left primary motor cortex and inferior parietal lobe between groups. Copyright © 2017 the American Physiological Society.

Is neuroplasticity in the central nervous system the missing link to our understanding of chronic musculoskeletal disorders?

PubMed

Pelletier, René; Higgins, Johanne; Bourbonnais, Daniel

2015-02-12

Musculoskeletal rehabilitative care and research have traditionally been guided by a structural pathology paradigm and directed their resources towards the structural, functional, and biological abnormalities located locally within the musculoskeletal system to understand and treat Musculoskeletal Disorders (MSD). However the structural pathology model does not adequately explain many of the clinical and experimental findings in subjects with chronic MSD and, more importantly, treatment guided by this paradigm fails to effectively treat many of these conditions. Increasing evidence reveals structural and functional changes within the Central Nervous System (CNS) of people with chronic MSD that appear to play a prominent role in the pathophysiology of these disorders. These neuroplastic changes are reflective of adaptive neurophysiological processes occurring as the result of altered afferent stimuli including nociceptive and neuropathic transmission to spinal, subcortical and cortical areas with MSD that are initially beneficial but may persist in a chronic state, may be part and parcel in the pathophysiology of the condition and the development and maintenance of chronic signs and symptoms. Neuroplastic changes within different areas of the CNS may help to explain the transition from acute to chronic conditions, sensory-motor findings, perceptual disturbances, why some individuals continue to experience pain when no structural cause can be discerned, and why some fail to respond to conservative interventions in subjects with chronic MSD. We argue that a change in paradigm is necessary that integrates CNS changes associated with chronic MSD and that these findings are highly relevant for the design and implementation of rehabilitative interventions for this population. Recent findings suggest that a change in model and approach is required in the rehabilitation of chronic MSD that integrate the findings of neuroplastic changes across the CNS and are targeted by rehabilitative interventions. Effects of current interventions may be mediated through peripheral and central changes but may not specifically address all underlying neuroplastic changes in the CNS potentially associated with chronic MSD. Novel approaches to address these neuroplastic changes show promise and require further investigation to improve efficacy of currents approaches.

Cognitive Remediation for the Treatment of Cognitive Dysfunction in the Early Course of Psychosis.

PubMed

Lewandowski, Kathryn E

2016-01-01

The development of cognitive remediation programs has been a key step toward the creation of a treatment approach to address the cognitive-symptom domain in psychosis. Studies support the efficacy of cognitive remediation in producing moderate effects on cognition at the group level in patients with schizophrenia. Cognitive remediation may harness neuroplasticity in relevant systems that underpin the cognitive functions being addressed. Since neuroplasticity may be greater in people who (1) are younger and (2) have not yet experienced the consequences of long-term psychosis, cognitive remediation may be particularly effective in people in the early course of illness or in the prodrome, prior to the onset of frank symptoms. The present article reviews the evidence for implementing cognitive remediation in patients with recent-onset psychosis and people identified as being at high risk for developing schizophrenia, and also the evidence for cognitive remediation to modify neural targets. Promising findings suggest that cognitive remediation may be useful in addressing cognitive deficits in early-course and prodromal participants. Additionally, a growing literature using neuroimaging techniques demonstrates the ability of cognitive remediation paradigms to engage neural targets.

Pharmacological and Behavioral Enhancement of Neuroplasticity in the MPTP-Lesioned Mouse and Nonhuman Primate

DTIC Science & Technology

2008-05-01

effect of amphetamine in mice neonatally lesioned with 6- hydroxydopamine. J Neurosci Res. 78, 289-96. 22 Berger-Sweeney, J., Stearns, N. A., Frick...through its effect on pre- and post- synaptic dopamine biosynthesis, uptake and receptor expression as well as glutamatergic synapses. This hypothesis...These studies were designed to be complementary in that both non-pharmacological and pharmacological effects of neuroplasticity are being

The role of Insulin-Like Growth Factor 1 (IGF-1) in brain development, maturation and neuroplasticity.

PubMed

Dyer, Adam H; Vahdatpour, Cyrus; Sanfeliu, Albert; Tropea, Daniela

2016-06-14

Insulin-Like Growth Factor 1 (IGF-1) is a phylogenetically ancient neurotrophic hormone with crucial roles to play in CNS development and maturation. Recently, IGF-1 has been shown to have potent effects on cellular neuroplasticity. Neuroplasticty refers to the adaptive changes made by the CNS in the face of changing functional demands and is crucial in processes such as learning and memory. IGF-1, signaling through its glycoprotein receptor (IGF-1R), and canonical signaling pathways such as the PI3K-Akt and Ras-Raf-MAP pathways, has potent effects on cellular neuroplasticity in the CNS. In the present review, the role of IGF-1 in brain development is reviewed, followed by a detailed discussion of the role played by IGF in cellular neuroplasticity in the CNS. Findings from models of perturbed and reparative plasticity detailing the role played by IGF-1 are discussed, followed by the electrophysiological, structural and functional evidence supporting this role. Finally, the post-lesion and post-injury roles played by IGF-1 are briefly evaluated. We discuss the putative neurobiology underlying these changes, reviewing recent evidence and highlighting areas for further research. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Catecholaminergic consolidation of motor cortical neuroplasticity in humans.

PubMed

Nitsche, Michael A; Grundey, Jessica; Liebetanz, David; Lang, Nicolas; Tergau, Frithjof; Paulus, Walter

2004-11-01

Amphetamine, a catecholaminergic re-uptake-blocker, is able to improve neuroplastic mechanisms in humans. However, so far not much is known about the underlying physiological mechanisms. Here, we study the impact of amphetamine on NMDA receptor-dependent long-lasting excitability modifications in the human motor cortex elicited by weak transcranial direct current stimulation (tDCS). Amphetamine significantly enhanced and prolonged increases in anodal, tDCS-induced, long-lasting excitability. Under amphetamine premedication, anodal tDCS resulted in an enhancement of excitability which lasted until the morning after tDCS, compared to approximately 1 h in the placebo condition. Prolongation of the excitability enhancement was most pronounced for long-term effects; the duration of short-term excitability enhancement was only slightly increased. Since the additional application of the NMDA receptor antagonist dextromethorphane blocked any enhancement of tDCS-driven excitability under amphetamine, we conclude that amphetamine consolidates the tDCS-induced neuroplastic effects, but does not initiate them. The fact that propanolol, a beta-adrenergic antagonist, diminished the duration of the tDCS-generated after-effects suggests that adrenergic receptors play a certain role in the consolidation of NMDA receptor-dependent motor cortical excitability modifications in humans. This result may enable researchers to optimize neuroplastic processes in the human brain on the rational basis of purpose-designed pharmacological interventions.

Differential tinnitus-related neuroplastic alterations of cortical thickness and surface area.

PubMed

Meyer, Martin; Neff, Patrick; Liem, Franziskus; Kleinjung, Tobias; Weidt, Steffi; Langguth, Berthold; Schecklmann, Martin

2016-12-01

Structural neuroimaging techniques have been used to identify cortical and subcortical regions constituting the neuroarchitecture of tinnitus. One recent investigation used voxel-based morphometry (VBM) to analyze a sample of tinnitus patients (TI, n = 257) (Schecklmann et al., 2013). A negative relationship between individual distress and cortical volume (CV) in bilateral auditory regions was observed. However, CV has meanwhile been identified as a neuroanatomical measurement that confounds genetically distinct neuroanatomical traits, namely cortical thickness (CT) and cortical surface area (CSA). We performed a re-analysis of the identical sample using the automated FreeSurfer surface-based morphometry (SBM) approach (Fischl, 2012). First, we replicated the negative correlation between tinnitus distress and bilateral supratemporal gray matter volume. Second, we observed a negative correlation for CSA in the left periauditory cortex and anterior insula. Furthermore, we noted a positive correlation between tinnitus duration and CT in the left periauditory cortex as well as a negative correlation in the subcallosal anterior cingulate, a region collated to the serotonergic circuit and germane to inhibitory functions. In short, the results elucidate differential neuroanatomical alterations of CSA and CT for the two independent tinnitus-related psychological traits distress and duration. Beyond this, the study provides further evidence for the distinction and specific susceptibility of CSA and CT within the context of neuroplasticity of the human brain. Copyright © 2016 Elsevier B.V. All rights reserved.

Neuroplasticity and Calcium Signaling in Stressed Rat Amygdala

DTIC Science & Technology

2005-02-01

kainate receptor and neuroplasticity in the amygdala. National Institute of aging, November, 2001. • He Li: GluR5 kainate receptor mediated synaptic...functions in the amygdala. National Institute of Mental Health, April, 2002. 50 " Maria F. M. Braga: Chronic Stress Causes Impairment of aI-Adrenoceptor...resistance All animal experiments were performed in accordance with of 1.5-5.0 Mf when filled with a solution containing (in our institutional guidelines

Natural Rewards, Neuroplasticity, and Non-Drug Addictions

PubMed Central

Olsen, Christopher M.

2011-01-01

There is a high degree of overlap between brain regions involved in processing natural rewards and drugs of abuse. “Non-drug” or “behavioral” addictions have become increasingly documented in the clinic, and pathologies include compulsive activities such as shopping, eating, exercising, sexual behavior, and gambling. Like drug addiction, non-drug addictions manifest in symptoms including craving, impaired control over the behavior, tolerance, withdrawal, and high rates of relapse. These alterations in behavior suggest that plasticity may be occurring in brain regions associated with drug addiction. In this review, I summarize data demonstrating that exposure to non-drug rewards can alter neural plasticity in regions of the brain that are affected by drugs of abuse. Research suggests that there are several similarities between neuroplasticity induced by natural and drug rewards and that, depending on the reward, repeated exposure to natural rewards might induce neuroplasticity that either promotes or counteracts addictive behavior. PMID:21459101

Oral biomarkers in exercise-induced neuroplasticity in Parkinson's disease.

PubMed

Mougeot, J-Lc; Hirsch, M A; Stevens, C B; Mougeot, Fkb

2016-11-01

In this article, we review candidate biomarkers for Parkinson's disease (PD) in oral cavity, potential of oral biomarkers as markers of neuroplasticity, and literature on the effects of exercise on oral cavity biomarkers in PD. We first describe how pathophysiological pathways of PD may be transduced from brain stem and ganglia to oral cavity through the autonomic nervous system or transduced by a reverse path. Next we describe the effects of exercise in PD and potential impact on oral cavity. We propose that biomarkers in oral cavity may be useful targets for describing exercise-induced brain neuroplasticity in PD. Nevertheless, much research remains to be carried out before applying these biomarkers for the determination of disease state and therapeutic response to develop strategies to mitigate motor or non-motor symptoms in PD. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The origin, and application of somatosensory evoked potentials as a neurophysiological technique to investigate neuroplasticity.

PubMed

Passmore, Steven R; Murphy, Bernadette; Lee, Timothy D

2014-06-01

Somatosensory evoked potentionals (SEPs) can be used to elucidate differences in cortical activity associated with a spinal manipulation (SM) intervention. The purpose of this narrative review is to overview the origin and application of SEPs, a neurophysiological technique to investigate neuroplasticity. Summaries of: 1) parameters for SEP generation and waveform recording; 2) SEP peak nomenclature, interpretation and generators; 3) peaks pertaining to tactile information processing (relevant to both chiropractic and other manual therapies); 4) utilization and application of SEPs; 5) SEPs concurrent with an experimental task and at baseline/control/pretest; 6) SEPs pain studies; and 7) SEPs design (pre/post) and neural reorganization/neuroplasticity; and 8) SEPs and future chiropractic research are all reviewed. Understanding what SEPs are, and their application allows chiropractors, educators, and other manual therapists interested in SM to understand the context, and importance of research findings from SM studies that involve SEPs.

Neuroplasticity of prehensile neural networks after quadriplegia.

PubMed

Di Rienzo, F; Guillot, A; Mateo, S; Daligault, S; Delpuech, C; Rode, G; Collet, C

2014-08-22

Targeting cortical neuroplasticity through rehabilitation-based practice is believed to enhance functional recovery after spinal cord injury (SCI). While prehensile performance is severely disturbed after C6-C7 SCI, subjects with tetraplegia can learn a compensatory passive prehension using the tenodesis effect. During tenodesis, an active wrist extension triggers a passive flexion of the fingers allowing grasping. We investigated whether motor imagery training could promote activity-dependent neuroplasticity and improve prehensile tenodesis performance. SCI participants (n=6) and healthy participants (HP, n=6) took part in a repeated measurement design. After an extended baseline period of 3 weeks including repeated magnetoencephalography (MEG) measurements, MI training was embedded within the classical course of physiotherapy for 5 additional weeks (three sessions per week). An immediate MEG post-test and a follow-up at 2 months were performed. Before MI training, compensatory activations and recruitment of deafferented cortical regions characterized the cortical activity during actual and imagined prehension in SCI participants. After MI training, MEG data yielded reduced compensatory activations. Cortical recruitment became similar to that in HP. Behavioral analysis evidenced decreased movement variability suggesting motor learning of tenodesis. Data suggest that MI training participated to reverse compensatory neuroplasticity in SCI participants, and promoted the integration of new upper limb prehensile coordination in the neural networks functionally dedicated to the control of healthy prehension before injury. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Genetics and pharmacogenetics of mood disorders.

PubMed

Serretti, Alessandro

2017-04-30

Genetic research in Psychiatry is viewed by clinicians with both hope and curiosity sometimes mixed with disillusionment. Indeed, in the last 30 years many results have not been confirmed and clinical applications are still missing. However recent findings suggest that we are at the beginning of a new era. A set of variants within neuroplasticity and inflammation genes have been identified as a valid basis for both bipolar disorder and major depression. Similarly, a set of genes has been identified as a liability factor for response and tolerability to antidepressants and the first clinical applications are already in the market. However, some caution should be applied until definite findings are available.

Mapping the dynamics of cortical neuroplasticity of skilled motor learning using micro X-ray fluorescence and histofluorescence imaging of zinc in the rat

PubMed Central

Alaverdashvili, Mariam; Paterson, Phyllis G.

2017-01-01

Synchrotron-based X-ray fluorescence imaging (XFI) of zinc (Zn) has been recently implemented to understand the efficiency of various therapeutic interventions targeting post-stroke neuroprotection and neuroplasticity. However, it is uncertain if micro XFI can resolve neuroplasticity-induced changes. Thus, we explored if learning-associated behavioral changes would be accompanied by changes in cortical Zn concentration measured by XFI in healthy adult rats. Proficiency in a skilled reach-to-eat task during early and late stages of motor learning served as a functional measure of neuroplasticity. c-Fos protein and vesicular Zn expression were employed as indirect neuronal measures of brain plasticity. A total Zn map (20 × 20 × 30 μm3 resolution) generated by micro XFI failed to reflect increases in either c-Fos or vesicular Zn in the motor cortex contralateral to the trained forelimb or improved proficiency in the skilled reaching task. Remarkably, vesicular Zn increased in the late stage of motor learning along with a concurrent decrease in the number of c-fos-ip neurons relative to the early stage of motor learning. This inverse dynamics of c-fos and vesicular Zn level as the motor skill advances suggest that a qualitatively different neural population, comprised of fewer active but more efficiently connected neurons, supports a skilled action in the late versus early stage of motor learning. The lack of sensitivity of the XFI-generated Zn map to visualize the plasticity-associated changes in vesicular Zn suggests that the Zn level measured by micro XFI should not be used as a surrogate marker of neuroplasticity in response to the acquisition of skilled motor actions. Nanoscopic XFI could be explored in future as a means of imaging these subtle physiological changes. PMID:27840249

Motor skill changes and neurophysiologic adaptation to recovery-oriented virtual rehabilitation of hand function in a person with subacute stroke: a case study.

PubMed

Fluet, Gerard G; Patel, Jigna; Qiu, Qinyin; Yarossi, Matthew; Massood, Supriya; Adamovich, Sergei V; Tunik, Eugene; Merians, Alma S

2017-07-01

The complexity of upper extremity (UE) behavior requires recovery of near normal neuromuscular function to minimize residual disability following a stroke. This requirement places a premium on spontaneous recovery and neuroplastic adaptation to rehabilitation by the lesioned hemisphere. Motor skill learning is frequently cited as a requirement for neuroplasticity. Studies examining the links between training, motor learning, neuroplasticity, and improvements in hand motor function are indicated. This case study describes a patient with slow recovering hand and finger movement (Total Upper Extremity Fugl-Meyer examination score = 25/66, Wrist and Hand items = 2/24 on poststroke day 37) following a stroke. The patient received an intensive eight-session intervention utilizing simulated activities that focused on the recovery of finger extension, finger individuation, and pinch-grasp force modulation. Over the eight sessions, the patient demonstrated improvements on untrained transfer tasks, which suggest that motor learning had occurred, as well a dramatic increase in hand function and corresponding expansion of the cortical motor map area representing several key muscles of the paretic hand. Recovery of hand function and motor map expansion continued after discharge through the three-month retention testing. This case study describes a neuroplasticity based intervention for UE hemiparesis and a model for examining the relationship between training, motor skill acquisition, neuroplasticity, and motor function changes. Implications for rehabilitation Intensive hand and finger rehabilitation activities can be added to an in-patient rehabilitation program for persons with subacute stroke. Targeted training of the thumb may have an impact on activity level function in persons with upper extremity hemiparesis. Untrained transfer tasks can be utilized to confirm that training tasks have elicited motor learning. Changes in cortical motor maps can be used to document changes in brain function which can be used to evaluate changes in motor behavior persons with subacute stroke.

Mild Thyroid Hormone Insufficiency During Development Compromises Activity-Dependent Neuroplasticity in the Hippocampus of Adult Male Rats

EPA Pesticide Factsheets

behavioral measures of learning and memory in adult offspring of rats treated with thyroid hormone synthesis inhibitor, propylthiouracil.Electrophysiological measures of 'memory' in form of plasticity model known as long term potentiation (LTP)Molecular changes induced by LTPThis dataset is associated with the following publication:Gilbert , M., K. Sanchez-Huerta, and C. Wood. Mild Thyroid Hormone Insufficiency During Development Compromises Activity-Dependent Neuroplasticity in the Hippocampus of Adult Make Rats. ENDOCRINOLOGY. Endocrine Society, 157(2): 774-87, (2016).

Phrenic motoneuron expression of serotonergic and glutamatergic receptors following upper cervical spinal cord injury

PubMed Central

Mantilla, Carlos B.; Bailey, Jeffrey P.; Zhan, Wen-Zhi; Sieck, Gary C.

2012-01-01

Following cervical spinal cord injury at C2 (SH hemisection model) there is progressive recovery of phrenic activity. Neuroplasticity in the postsynaptic expression of neurotransmitter receptors may contribute to functional recovery. Phrenic motoneurons express multiple serotonergic (5-HTR) and glutamatergic (GluR) receptors, but the timing and possible role of these different neurotransmitter receptor subtypes in the neuroplasticity following SH are not clear. The current study was designed to test the hypothesis that there is an increased expression of serotonergic and glutamatergic neurotransmitter receptors within phrenic motoneurons after SH. In adult male rats, phrenic motoneurons were labeled retrogradely by intrapleural injection of Alexa 488-conjugated cholera toxin B. In thin (10 μm) frozen sections of the spinal cord, fluorescently-labeled phrenic motoneurons were visualized for laser capture microdissection (LCM). Using quantitative real-time RT-PCR in LCM samples, the time course of changes in 5-HTR and GluR mRNA expression was determined in phrenic motoneurons up to 21 days post-SH. Expression of 5-HTR subtypes 1b, 2a and 2c and GluR subtypes AMPA, NMDA, mGluR1 and mGluR5 was evident in phrenic motoneurons from control and SH rats. Phrenic motoneuron expression of 5-HTR2a increased ~8-fold (relative to control) at 14 days post-SH, whereas NMDA expression increased ~16-fold by 21-days post-SH. There were no other significant changes in receptor expression at any time post-SH. This is the first study to systematically document changes in motoneuron expression of multiple neurotransmitter receptors involved in regulation of motoneuron excitability. By providing information on the neuroplasticity of receptors expressed in a motoneuron pool that is inactivated by a higher-level spinal cord injury, appropriate pharmacological targets can be identified to alter motoneuron excitability. PMID:22227062

Assessing and inducing neuroplasticity with transcranial magnetic stimulation and robotics for motor function.

PubMed

O'Malley, Marcia K; Ro, Tony; Levin, Harvey S

2006-12-01

To describe 2 new ways of assessing and inducing neuroplasticity in the human brain--transcranial magnetic stimulation (TMS) and robotics--and to investigate and promote the recovery of motor function after brain damage. We identified recent articles and books directly bearing on TMS and robotics. Articles using these tools for purposes other than rehabilitation were excluded. From these studies, we emphasize the methodologic and technical details of these tools as applicable for assessing and inducing plasticity. Because both tools have only recently been used for rehabilitation, the majority of the articles selected for this review have been published only within the last 10 years. We used the PubMed and Compendex databases to find relevant peer-reviewed studies for this review. The studies were required to be relevant to rehabilitation and to use TMS or robotics methodologies. Guidelines were applied via independent extraction by multiple observers. Despite the limited amount of research using these procedures for assessing and inducing neuroplasticity, there is growing evidence that both TMS and robotics can be very effective, inexpensive, and convenient ways for assessing and inducing rehabilitation. Although TMS has primarily been used as an assessment tool for motor function, an increasing number of studies are using TMS as a tool to directly induce plasticity and improve motor function. Similarly, robotic devices have been used for rehabilitation because of their suitability for delivery of highly repeatable training. New directions in robotics-assisted rehabilitation are taking advantage of novel measurements that can be acquired via the devices, enabling unique methods of assessment of motor recovery. As refinements in technology and advances in our knowledge continue, TMS and robotics should play an increasing role in assessing and promoting the recovery of function. Ongoing and future studies combining TMS and robotics within the same populations may prove fruitful for a more detailed and comprehensive assessment of the central and peripheral changes in the nervous system during precisely induced recovery.

Musical training, neuroplasticity and cognition.

PubMed

Rodrigues, Ana Carolina; Loureiro, Maurício Alves; Caramelli, Paulo

2010-01-01

The influence of music on the human brain has been recently investigated in numerous studies. Several investigations have shown that structural and functional cerebral neuroplastic processes emerge as a result of long-term musical training, which in turn may produce cognitive differences between musicians and non-musicians. Musicians can be considered ideal cases for studies on brain adaptation, due to their unique and intensive training experiences. This article presents a review of recent findings showing positive effects of musical training on non-musical cognitive abilities, which probably reflect plastic changes in brains of musicians.

Neuroplastic changes in the sensorimotor cortex associated with orthodontic tooth movement in rats.

PubMed

Sood, Mandeep; Lee, Jye-Chang; Avivi-Arber, Limor; Bhatt, Poolak; Sessle, Barry J

2015-07-01

Orthodontic tooth movement (OTM) causes transient pain and changes in the dental occlusion that may lead to altered somatosensory inputs and patterns of mastication. This study used intracortical microstimulation (ICMS) and electromyographic (EMG) recordings to test whether neuroplastic changes occur in the ICMS-defined motor representations of left and right anterior digastric (LAD, RAD), masseter, buccinator, and genioglossus (GG) muscles within the rat's face primary motor cortex (face-M1) and adjacent face primary somatosensory cortex (face-S1) during OTM. Analyses included any changes in the number of ICMS sites representing these muscles and in the onset latencies of ICMS-evoked responses in the muscles. Sprague-Dawley rats were divided into experimental (E), sham (S), and naive (N) groups; OTM was induced in the E group. Statistical analyses involved a mixed model repeated-measures analysis of variance (MMRM ANOVA). OTM resulted in significant neuroplastic changes in the number of positive sites in the E group for LAD, RAD, and GG muscles in face-M1 and face-S1 at days 1, 7, and 28 of continuous orthodontic force application, and in the number of sites in face-M1 from which ICMS could simultaneously evoke EMG responses in different combinations of LAD, RAD, and GG muscles. However, the onset latencies of ICMS-evoked responses were not significantly different between groups or between face-M1 and face-S1. The neuroplastic changes documented in this study may reflect adaptive sensorimotor changes in response to the altered environment in the oral cavity induced by OTM. © 2015 Wiley Periodicals, Inc.

Structural but not functional neuroplasticity one year after effective cognitive behaviour therapy for social anxiety disorder.

PubMed

Månsson, Kristoffer N T; Salami, Alireza; Carlbring, Per; Boraxbekk, C-J; Andersson, Gerhard; Furmark, Tomas

2017-02-01

Effective psychiatric treatments ameliorate excessive anxiety and induce neuroplasticity immediately after the intervention, indicating that emotional components in the human brain are rapidly adaptable. Still, the interplay between structural and functional neuroplasticity is poorly understood, and studies of treatment-induced long-term neuroplasticity are rare. Functional and structural magnetic resonance imaging (using 3T MRI) was performed in 13 subjects with social anxiety disorder on 3 occasions over 1year. All subjects underwent 9 weeks of Internet-delivered cognitive behaviour therapy in a randomized cross-over design and independent assessors used the Clinically Global Impression-Improvement (CGI-I) scale to determine treatment response. Gray matter (GM) volume, assessed with voxel-based morphometry, and functional blood-oxygen level-dependent (BOLD) responsivity to self-referential criticism were compared between treatment responders and non-responders using 2×2 (group×time; pretreatment to follow-up) ANOVA. At 1-year follow-up, 7 (54%) subjects were classified as CGI-I responders. Left amygdala GM volume was more reduced in responders relative to non-responders from pretreatment to 1-year follow-up (Z=3.67, Family-Wise Error corrected p=0.02). In contrast to previous short-term effects, altered BOLD activations to self-referential criticism did not separate responder groups at follow-up. The structure and function of the amygdala changes immediately after effective psychological treatment of social anxiety disorder, but only reduced amygdala GM volume, and not functional activity, is associated with a clinical response 1year after CBT. Copyright © 2016 Elsevier B.V. All rights reserved.

Evolution of Neuroplasticity in Response to Physical Activity in Old Age: The Case for Dancing

PubMed Central

Müller, Patrick; Rehfeld, Kathrin; Schmicker, Marlen; Hökelmann, Anita; Dordevic, Milos; Lessmann, Volkmar; Brigadski, Tanja; Kaufmann, Jörn; Müller, Notger G.

2017-01-01

From animal research, it is known that combining physical activity with sensory enrichment has stronger and longer-lasting effects on the brain than either treatment alone. For humans dancing has been suggested to be analogous to such combined training. Here we assessed whether a newly designed dance training program that stresses the constant learning of new movement patterns is superior in terms of neuroplasticity to conventional fitness activities with repetitive exercises and whether extending the training duration has additional benefits. Twenty-two healthy seniors (63–80 years) who had been randomly assigned to either a dance or a sport group completed the entire 18-month study. MRI, BDNF and neuropsychological tests were performed at baseline and after 6 and 18 months of intervention. After 6 months, we found a significant increase in gray matter volume in the left precentral gyrus in the dancers compared to controls. This neuroplasticity effect may have been mediated by the increased BDNF plasma levels observed in the dancers. Regarding cognitive measures, both groups showed significant improvements in attention after 6 months and in verbal memory after 18 months. In addition, volume increases in the parahippocampal region were observed in the dancers after 18 months. The results of our study suggest that participating in a long-term dance program that requires constant cognitive and motor learning is superior to engaging in repetitive physical exercises in inducing neuroplasticity in the brains of seniors. Therefore, dance is highly promising in its potential to counteract age-related gray matter decline. PMID:28352225

Exercise Induced Neuroplasticity to Enhance Therapeutic Outcomes of Cognitive Remediation in Schizophrenia: Analyzing the Role of Brai nderived Neurotrophic Factor.

PubMed

Campos, Carlos; Rocha, Nuno B F; Lattari, Eduardo; Nardi, Antonio E; Machado, Sergio

2017-01-01

Cognitive impairment is a major manifestation of schizophrenia and a crucial treatment target as these deficits are closely related to patients' functional outcomes. Cognitive remediation is the gold-standard practice to address cognitive deficits in schizophrenia. There is clear evidence stating that cognitive remediation improves cognitive function and promotes structural neuroplastic changes in patients with schizophrenia, with brain-derived neurotrophic factor (BDNF) expression emerging as a potential biomarker for its efficacy. This is particularly important as there is clear evidence relating atypical BDNF expression to cognitive impairment in patients with schizophrenia. Despite the valuable role of cognitive remediation in the management of schizophrenia, there is still a need to develop methods that allow maximizing its efficacy. In this review, we present a hypothesis arguing that cognitive remediation efficacy for patients with schizophrenia can be enhanced by aerobic exercise-induced BDNF upregulation. There have been a few trials reporting that combining aerobic exercise with cognitive training was superior to cognitive training alone to improve cognitive functioning in patients with schizophrenia. Furthermore, there is preliminary evidence suggesting that combined aerobic and cognitive training can increase peripheral BDNF levels. Thereby, engaging in aerobic exercise in close temporal proximity to cognitive remediation may allow achieving a state of neuroplastic readiness in the brain, facilitating cognitive functioning enhancement. Although this hypothesis still lacks evidence, future clinical trials using cognitive remediation for schizophrenia should explore strategies to maximize neuroplasticity and achieve optimal cognitive improvements. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Cortical Plasticity in Depression

PubMed Central

Cantone, Mariagiovanna; Bramanti, Alessia; Pennisi, Manuela; Bramanti, Placido; Pennisi, Giovanni; Bella, Rita

2017-01-01

Neural plasticity is considered the neurophysiological correlate of learning and memory, although several studies have also noted that it plays crucial roles in a number of neurological and psychiatric diseases. Indeed, impaired brain plasticity may be one of the pathophysiological mechanisms that underlies both cognitive decline and major depression. Moreover, a degree of cognitive impairment is frequently observed throughout the clinical spectrum of mood disorders, and the relationship between depression and cognition is often bidirectional. However, most evidence for dysfunctional neural plasticity in depression has been indirect. Transcranial magnetic stimulation has emerged as a noninvasive tool for investigating several parameters of cortical excitability with the aim of exploring the functions of different neurotransmission pathways and for probing in vivo plasticity in both healthy humans and those with pathological conditions. In particular, depressed patients exhibit a significant interhemispheric difference in motor cortex excitability, an imbalanced inhibitory or excitatory intracortical neurochemical circuitry, reduced postexercise facilitation, and an impaired long-term potentiation-like response to paired-associative transcranial magnetic stimulation, and these symptoms may indicate disrupted plasticity. Research aimed at disentangling the mechanism by which neuroplasticity plays a role in the pathological processes that lead to depression and evaluating the effects of modulating neuroplasticity are needed for the field to facilitate more powerful translational research studies and identify novel therapeutic targets. PMID:28629225

Variability of Neuronal Responses: Types and Functional Significance in Neuroplasticity and Neural Darwinism

PubMed Central

Chervyakov, Alexander V.; Sinitsyn, Dmitry O.; Piradov, Michael A.

2016-01-01

HIGHLIGHTS We suggest classifying variability of neuronal responses as follows: false (associated with a lack of knowledge about the influential factors), “genuine harmful” (noise), “genuine neutral” (synonyms, repeats), and “genuine useful” (the basis of neuroplasticity and learning).The genuine neutral variability is considered in terms of the phenomenon of degeneracy.Of particular importance is the genuine useful variability that is considered as a potential basis for neuroplasticity and learning. This type of variability is considered in terms of the neural Darwinism theory. In many cases, neural signals detected under the same external experimental conditions significantly change from trial to trial. The variability phenomenon, which complicates extraction of reproducible results and is ignored in many studies by averaging, has attracted attention of researchers in recent years. In this paper, we classify possible types of variability based on its functional significance and describe features of each type. We describe the key adaptive significance of variability at the neural network level and the degeneracy phenomenon that may be important for learning processes in connection with the principle of neuronal group selection. PMID:27932969

Variability of Neuronal Responses: Types and Functional Significance in Neuroplasticity and Neural Darwinism.

PubMed

Chervyakov, Alexander V; Sinitsyn, Dmitry O; Piradov, Michael A

2016-01-01

HIGHLIGHTS We suggest classifying variability of neuronal responses as follows: false (associated with a lack of knowledge about the influential factors), "genuine harmful" (noise), "genuine neutral" (synonyms, repeats), and "genuine useful" (the basis of neuroplasticity and learning).The genuine neutral variability is considered in terms of the phenomenon of degeneracy.Of particular importance is the genuine useful variability that is considered as a potential basis for neuroplasticity and learning. This type of variability is considered in terms of the neural Darwinism theory. In many cases, neural signals detected under the same external experimental conditions significantly change from trial to trial. The variability phenomenon, which complicates extraction of reproducible results and is ignored in many studies by averaging, has attracted attention of researchers in recent years. In this paper, we classify possible types of variability based on its functional significance and describe features of each type. We describe the key adaptive significance of variability at the neural network level and the degeneracy phenomenon that may be important for learning processes in connection with the principle of neuronal group selection.

Influence of Aerobic Training and Combinations of Interventions on Cognition and Neuroplasticity after Stroke

PubMed Central

Constans, Annabelle; Pin-barre, Caroline; Temprado, Jean-Jacques; Decherchi, Patrick; Laurin, Jérôme

2016-01-01

Stroke often aggravated age-related cognitive impairments that strongly affect several aspects of quality of life. However, few studies are, to date, focused on rehabilitation strategies that could improve cognition. Among possible interventions, aerobic training is well known to enhance cardiovascular and motor functions but may also induce beneficial effects on cognitive functions. To assess the effectiveness of aerobic training on cognition, it seems necessary to know whether training promotes the neuroplasticity in brain areas involved in cognitive functions. In the present review, we first explore in both human and animal how aerobic training could improve cognition after stroke by highlighting the neuroplasticity mechanisms. Then, we address the potential effect of combinations between aerobic training with other interventions, including resistance exercises and pharmacological treatments. In addition, we postulate that classic recommendations for aerobic training need to be reconsidered to target both cognition and motor recovery because the current guidelines are only focused on cardiovascular and motor recovery. Finally, methodological limitations of training programs and cognitive function assessment are also developed in this review to clarify their effectiveness in stroke patients. PMID:27445801

Interventional programmes to improve cognition during healthy and pathological ageing: Cortical modulations and evidence for brain plasticity.

PubMed

Cespón, Jesús; Miniussi, Carlo; Pellicciari, Maria Concetta

2018-05-01

A growing body of evidence suggests that healthy elderly individuals and patients with Alzheimer's disease retain an important potential for neuroplasticity. This review summarizes studies investigating the modulation of neural activity and structural brain integrity in response to interventions involving cognitive training, physical exercise and non-invasive brain stimulation in healthy elderly and cognitively impaired subjects (including patients with mild cognitive impairment (MCI) and Alzheimer's disease). Moreover, given the clinical relevance of neuroplasticity, we discuss how evidence for neuroplasticity can be inferred from the functional and structural brain changes observed after implementing these interventions. We emphasize that multimodal programmes, which combine several types of interventions, improve cognitive function to a greater extent than programmes that use a single interventional approach. We suggest specific methods for weighting the relative importance of cognitive training, physical exercise and non-invasive brain stimulation according to the functional and structural state of the brain of the targeted subject to maximize the cognitive improvements induced by multimodal programmes. Copyright © 2018 Elsevier B.V. All rights reserved.

Response contingency directs long-term cocaine-induced neuroplasticity in prefrontal and striatal dopamine terminals.

PubMed

Wiskerke, Joost; Schoffelmeer, Anton N M; De Vries, Taco J

2016-10-01

Exposure to addictive substances such as cocaine is well-known to alter brain organisation. Cocaine-induced neuroadaptations depend on several factors, including drug administration paradigm. To date, studies addressing the consequences of cocaine exposure on dopamine transmission have either not been designed to investigate the role of response contingency or focused only on short-term neuroplasticity. We demonstrate a key role of response contingency in directing long-term cocaine-induced neuroplasticity throughout projection areas of the mesocorticolimbic dopamine system. We found enhanced electrically-evoked [(3)H]dopamine release from superfused brain slices of nucleus accumbens shell and core, dorsal striatum and medial prefrontal cortex three weeks after cessation of cocaine self-administration. In yoked cocaine rats receiving the same amount of cocaine passively, sensitised dopamine terminal reactivity was only observed in the nucleus accumbens core. Control sucrose self-administration experiments demonstrated that the observed neuroadaptations were not the result of instrumental learning per se. Thus, long-term withdrawal from cocaine self-administration is associated with widespread sensitisation of dopamine terminals throughout frontostriatal circuitries. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Harnessing the power of neuroplasticity for intervention

PubMed Central

Kolb, Bryan; Muhammad, Arif

2014-01-01

A fundamental property of the brain is its capacity to change with a wide variety of experiences, including injury. Although there are spontaneous reparative changes following injury, these changes are rarely sufficient to support significant functional recovery. Research on the basic principles of brain plasticity is leading to new approaches to treating the injured brain. We review factors that affect synaptic organization in the normal brain, evidence of spontaneous neuroplasticity after injury, and the evidence that factors including postinjury experience, pharmacotherapy, and cell-based therapies, can form the basis of rehabilitation strategies after brain injuries early in life and in adulthood. PMID:25018713

[Neuroplasticity as a basis for early rehabilitation of stroke patients].

PubMed

Putilina, M V

2011-01-01

The review is devoted to the current state of the problem of early rehabilitation of stroke patients. The rate of primary disability in patients after stroke is 3.2 per 10000 population but only 20% of previously working patients return to work. Early rehabilitation is treatment actions during a period following stroke. Adequate treatment during this period may decrease the extent of brain damage and improve disease outcome. The complexity of rehabilitation consists in using several complementary pharmacological and non-pharmacological rehabilitation measures. Appearance of new techniques of rehabilitation treatment aimed at neuroplasticity stimulation increases treatment potential of rehabilitative technologies.

Relationships among cognition, emotion, and motivation: implications for intervention and neuroplasticity in psychopathology.

PubMed

Crocker, Laura D; Heller, Wendy; Warren, Stacie L; O'Hare, Aminda J; Infantolino, Zachary P; Miller, Gregory A

2013-01-01

Emotion-cognition and motivation-cognition relationships and related brain mechanisms are receiving increasing attention in the clinical research literature as a means of understanding diverse types of psychopathology and improving biological and psychological treatments. This paper reviews and integrates some of the growing evidence for cognitive biases and deficits in depression and anxiety, how these disruptions interact with emotional and motivational processes, and what brain mechanisms appear to be involved. This integration sets the stage for understanding the role of neuroplasticity in implementing change in cognitive, emotional, and motivational processes in psychopathology as a function of intervention.

Long-Term Moderate Exercise Rescues Age-Related Decline in Hippocampal Neuronal Complexity and Memory.

PubMed

Tsai, Sheng-Feng; Ku, Nai-Wen; Wang, Tzu-Feng; Yang, Yan-Hsiang; Shih, Yao-Hsiang; Wu, Shih-Ying; Lee, Chu-Wan; Yu, Megan; Yang, Ting-Ting; Kuo, Yu-Min

2018-05-07

Aging impairs hippocampal neuroplasticity and hippocampus-related learning and memory. In contrast, exercise training is known to improve hippocampal neuronal function. However, whether exercise is capable of restoring memory function in old animals is less clear. Here, we investigated the effects of exercise on the hippocampal neuroplasticity and memory functions during aging. Young (3 months), middle-aged (9-12 months), and old (18 months) mice underwent moderate-intensity treadmill running training for 6 weeks, and their hippocampus-related learning and memory, and the plasticity of their CA1 neurons was evaluated. The memory performance (Morris water maze and novel object recognition tests), and dendritic complexity (branch and length) and spine density of their hippocampal CA1 neurons decreased as their age increased. The induction and maintenance of high-frequency stimulation-induced long-term potentiation in the CA1 area and the expressions of neuroplasticity-related proteins were not affected by age. Treadmill running increased CA1 neuron long-term potentiation and dendritic complexity in all three age groups, and it restored the learning and memory ability in middle-aged and old mice. Furthermore, treadmill running upregulated the hippocampal expressions of brain-derived neurotrophic factor and monocarboxylate transporter-4 in middle-aged mice, glutamine synthetase in old mice, and full-length TrkB in middle-aged and old mice. The hippocampus-related memory function declines from middle age, but long-term moderate-intensity running effectively increased hippocampal neuroplasticity and memory in mice of different ages, even when the memory impairment had progressed to an advanced stage. Thus, long-term, moderate intensity exercise training might be a way of delaying and treating aging-related memory decline. © 2018 S. Karger AG, Basel.

Brain stimulation-induced neuroplasticity underlying therapeutic response in phantom sounds.

PubMed

Poeppl, Timm B; Langguth, Berthold; Lehner, Astrid; Frodl, Thomas; Rupprecht, Rainer; Kreuzer, Peter M; Landgrebe, Michael; Schecklmann, Martin

2018-01-01

Noninvasive brain stimulation can modify phantom sounds for longer periods by modulating neural activity and putatively inducing regional neuroplastic changes. However, treatment response is limited and there are no good demographic or clinical predictors for treatment outcome. We used state-of-the-art voxel-based morphometry (VBM) to investigate whether transcranial magnetic stimulation-induced neuroplasticity determines therapeutic outcome. Sixty subjects chronically experiencing phantom sounds (i.e., tinnitus) received repetitive transcranial magnetic stimulation (rTMS) of left dorsolateral prefrontal and temporal cortex according to a protocol that has been shown to yield a significantly higher number of treatment responders than sham stimulation and previous stimulation protocols. Structural magnetic resonance imaging was performed before and after rTMS. In VBM whole-brain analyses (P < 0.05, FWE corrected), we assessed longitudinal gray matter changes as well as structural connectivity between the ensuing regions. We observed longitudinal mesoscopic gray matter changes of left dorsolateral prefontal (DLPFC), left operculo-insular, and right inferior temporal cortex (ITC) in responders (N = 22) but not nonresponders (N = 38), as indicated by a group × time interaction and post-hoc tests. These results were neither influenced by age, sex, hearing loss nor by tinnitus laterality, duration, and severity at baseline. Furthermore, we found robust DLPFC-insula and insula-ITC connectivity in responders, while only relatively weak DLPFC-insula connectivity and no insula-ITC connectivity could be demonstrated in nonresponders. Our results reinforce the implication of nonauditory brain regions in phantom sounds and suggest the dependence of therapeutic response on their neuroplastic capabilities. The latter in turn may depend on (differences in) their individual structural connectivity. Hum Brain Mapp 39:554-562, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Physical exercise prevents cognitive impairment by enhancing hippocampal neuroplasticity and mitochondrial function in doxorubicin-induced chemobrain.

PubMed

Park, Hye-Sang; Kim, Chang-Ju; Kwak, Hyo-Bum; No, Mi-Hyun; Heo, Jun-Won; Kim, Tae-Woon

2018-05-01

Although chemotherapy increases the survival rate of patients with various cancers, such treatment can induce acute or long-term cognitive dysfunction a phenomenon known as post-chemotherapy cognitive impairment (PCCI) or "chemobrain." Exercise is known to positively affect brain function. Thus, the present study aimed to determine whether symptoms of chemobrain and disruptions in the neuroplasticity and functioning of hippocampal mitochondria can be prevented or relieved by exercise. Wistar rats were separated into the following groups: control, control plus exercise, chemobrain, and chemobrain plus exercise. For chemobrain induction, 2 mg/kg of doxorubicin (DOX) a widely utilized chemotherapeutic agent among patients with breast cancer was dissolved in saline and directly injected to the abdomen once every 4 weeks. The exercise groups were subjected to low-intensity treadmill, 6 days per week for 4 weeks. The Morris water maze and step-down avoidance tests were conducted to evaluate cognitive function, while neuroplasticity and mitochondrial function were assessed in the hippocampus and dentate gyrus. Decreased cognitive function were observed in the chemobrain group, along with decreases in levels of neurogenesis, brain derived neurotrophic factor (BDNF), tropomyosin-related kinase B (TrkB), Ca 2+ retention in hippocampus. Rats of the chemobrain group also exhibited an increase in apoptosis, H 2 O 2 emission and permeability transition pore by hippocampal mitochondria. However, exercise attenuated impairments in cognitive function, neuroplasticity, and mitochondrial function induced by DOX treatment. Therefore, the findings of the present study indicate that low-intensity exercise may assist in preventing cognitive dysfunction during or after chemotherapy in patients with various cancers, including breast cancer. Copyright © 2018 Elsevier Ltd. All rights reserved.

Structural brain correlates associated with professional handball playing.

PubMed

Hänggi, Jürgen; Langer, Nicolas; Lutz, Kai; Birrer, Karin; Mérillat, Susan; Jäncke, Lutz

2015-01-01

There is no doubt that good bimanual performance is very important for skilled handball playing. The control of the non-dominant hand is especially demanding since efficient catching and throwing needs both hands. We investigated training-induced structural neuroplasticity in professional handball players using several structural neuroimaging techniques and analytic approaches and also provide a review of the literature about sport-induced structural neuroplastic alterations. Structural brain adaptations were expected in regions relevant for motor and somatosensory processing such as the grey matter (GM) of the primary/secondary motor (MI/supplementary motor area, SMA) and somatosensory cortex (SI/SII), basal ganglia, thalamus, and cerebellum and in the white matter (WM) of the corticospinal tract (CST) and corpus callosum, stronger in brain regions controlling the non-dominant left hand. Increased GM volume in handball players compared with control subjects were found in the right MI/SI, bilateral SMA/cingulate motor area, and left intraparietal sulcus. Fractional anisotropy (FA) and axial diffusivity were increased within the right CST in handball players compared with control women. Age of handball training commencement correlated inversely with GM volume in the right and left MI/SI and years of handball training experience correlated inversely with radial diffusivity in the right CST. Subcortical structures tended to be larger in handball players. The anatomical measures of the brain regions associated with handball playing were positively correlated in handball players, but not interrelated in control women. Training-induced structural alterations were found in the somatosensory-motor network of handball players, more pronounced in the right hemisphere controlling the non-dominant left hand. Correlations between handball training-related measures and anatomical differences suggest neuroplastic adaptations rather than a genetic predisposition for a ball playing affinity. Investigations of neuroplasticity specifically in sportsmen might help to understand the neural mechanisms of expertise in general.

Exercise-induced neuronal plasticity in central autonomic networks: role in cardiovascular control.

PubMed

Michelini, Lisete C; Stern, Javier E

2009-09-01

It is now well established that brain plasticity is an inherent property not only of the developing but also of the adult brain. Numerous beneficial effects of exercise, including improved memory, cognitive function and neuroprotection, have been shown to involve an important neuroplastic component. However, whether major adaptive cardiovascular adjustments during exercise, needed to ensure proper blood perfusion of peripheral tissues, also require brain neuroplasticity, is presently unknown. This review will critically evaluate current knowledge on proposed mechanisms that are likely to underlie the continuous resetting of baroreflex control of heart rate during/after exercise and following exercise training. Accumulating evidence indicates that not only somatosensory afferents (conveyed by skeletal muscle receptors, baroreceptors and/or cardiopulmonary receptors) but also projections arising from central command neurons (in particular, peptidergic hypothalamic pre-autonomic neurons) converge into the nucleus tractus solitarii (NTS) in the dorsal brainstem, to co-ordinate complex cardiovascular adaptations during dynamic exercise. This review focuses in particular on a reciprocally interconnected network between the NTS and the hypothalamic paraventricular nucleus (PVN), which is proposed to act as a pivotal anatomical and functional substrate underlying integrative feedforward and feedback cardiovascular adjustments during exercise. Recent findings supporting neuroplastic adaptive changes within the NTS-PVN reciprocal network (e.g. remodelling of afferent inputs, structural and functional neuronal plasticity and changes in neurotransmitter content) will be discussed within the context of their role as important underlying cellular mechanisms supporting the tonic activation and improved efficacy of these central pathways in response to circulatory demand at rest and during exercise, both in sedentary and in trained individuals. We hope this review will stimulate more comprehensive studies aimed at understanding cellular and molecular mechanisms within CNS neuronal networks that contribute to exercise-induced neuroplasticity and cardiovascular adjustments.

Relationships among cognition, emotion, and motivation: implications for intervention and neuroplasticity in psychopathology

PubMed Central

Crocker, Laura D.; Heller, Wendy; Warren, Stacie L.; O'Hare, Aminda J.; Infantolino, Zachary P.; Miller, Gregory A.

2013-01-01

Emotion-cognition and motivation-cognition relationships and related brain mechanisms are receiving increasing attention in the clinical research literature as a means of understanding diverse types of psychopathology and improving biological and psychological treatments. This paper reviews and integrates some of the growing evidence for cognitive biases and deficits in depression and anxiety, how these disruptions interact with emotional and motivational processes, and what brain mechanisms appear to be involved. This integration sets the stage for understanding the role of neuroplasticity in implementing change in cognitive, emotional, and motivational processes in psychopathology as a function of intervention. PMID:23781184

Neurophysiology of Robot-Mediated Training and Therapy: A Perspective for Future Use in Clinical Populations

PubMed Central

Turner, Duncan L.; Ramos-Murguialday, Ander; Birbaumer, Niels; Hoffmann, Ulrich; Luft, Andreas

2013-01-01

The recovery of functional movements following injury to the central nervous system (CNS) is multifaceted and is accompanied by processes occurring in the injured and non-injured hemispheres of the brain or above/below a spinal cord lesion. The changes in the CNS are the consequence of functional and structural processes collectively termed neuroplasticity and these may occur spontaneously and/or be induced by movement practice. The neurophysiological mechanisms underlying such brain plasticity may take different forms in different types of injury, for example stroke vs. spinal cord injury (SCI). Recovery of movement can be enhanced by intensive, repetitive, variable, and rewarding motor practice. To this end, robots that enable or facilitate repetitive movements have been developed to assist recovery and rehabilitation. Here, we suggest that some elements of robot-mediated training such as assistance and perturbation may have the potential to enhance neuroplasticity. Together the elemental components for developing integrated robot-mediated training protocols may form part of a neurorehabilitation framework alongside those methods already employed by therapists. Robots could thus open up a wider choice of options for delivering movement rehabilitation grounded on the principles underpinning neuroplasticity in the human CNS. PMID:24312073

The Case for Musical Instrument Training in Cerebral Palsy for Neurorehabilitation

PubMed Central

2016-01-01

Recent imaging studies in cerebral palsy (CP) have described several brain structural changes, functional alterations, and neuroplastic processes that take place after brain injury during early development. These changes affect motor pathways as well as sensorimotor networks. Several of these changes correlate with behavioral measures of motor and sensory disability. It is now widely acknowledged that management of sensory deficits is relevant for rehabilitation in CP. Playing a musical instrument demands the coordination of hand movements with integrated auditory, visual, and tactile feedback, in a process that recruits multiple brain regions. These multiple demands during instrument playing, together with the entertaining character of music, have led to the development and investigation of music-supported therapies, especially for rehabilitation with motor disorders resulting from brain damage. We review scientific evidence that supports the use of musical instrument playing for rehabilitation in CP. We propose that active musical instrument playing may be an efficient means for triggering neuroplastic processes necessary for the development of sensorimotor skills in patients with early brain damage. We encourage experimental research on neuroplasticity and on its impact on the physical and personal development of individuals with CP. PMID:27867664

The Case for Musical Instrument Training in Cerebral Palsy for Neurorehabilitation.

PubMed

Alves-Pinto, Ana; Turova, Varvara; Blumenstein, Tobias; Lampe, Renée

2016-01-01

Recent imaging studies in cerebral palsy (CP) have described several brain structural changes, functional alterations, and neuroplastic processes that take place after brain injury during early development. These changes affect motor pathways as well as sensorimotor networks. Several of these changes correlate with behavioral measures of motor and sensory disability. It is now widely acknowledged that management of sensory deficits is relevant for rehabilitation in CP. Playing a musical instrument demands the coordination of hand movements with integrated auditory, visual, and tactile feedback, in a process that recruits multiple brain regions. These multiple demands during instrument playing, together with the entertaining character of music, have led to the development and investigation of music-supported therapies, especially for rehabilitation with motor disorders resulting from brain damage. We review scientific evidence that supports the use of musical instrument playing for rehabilitation in CP. We propose that active musical instrument playing may be an efficient means for triggering neuroplastic processes necessary for the development of sensorimotor skills in patients with early brain damage. We encourage experimental research on neuroplasticity and on its impact on the physical and personal development of individuals with CP.

Respiratory modulation of human autonomic function: long‐term neuroplasticity in space

PubMed Central

Diedrich, André; Cooke, William H.; Biaggioni, Italo; Buckey, Jay C.; Pawelczyk, James A.; Ertl, Andrew C.; Cox, James F.; Kuusela, Tom A.; Tahvanainen, Kari U.O.; Mano, Tadaaki; Iwase, Satoshi; Baisch, Friedhelm J.; Levine, Benjamin D.; Adams‐Huet, Beverley; Robertson, David; Blomqvist, C. Gunnar

2016-01-01

Key points We studied healthy astronauts before, during and after the Neurolab Space Shuttle mission with controlled breathing and apnoea, to identify autonomic changes that might contribute to postflight orthostatic intolerance.Measurements included the electrocardiogram, finger photoplethysmographic arterial pressure, respiratory carbon dioxide levels, tidal volume and peroneal nerve muscle sympathetic activity.Arterial pressure fell and then rose in space, and drifted back to preflight levels after return to Earth.Vagal metrics changed in opposite directions: vagal baroreflex gain and two indices of vagal fluctuations rose and then fell in space, and descended to preflight levels upon return to Earth.Sympathetic burst frequencies (but not areas) were greater than preflight in space and on landing day, and astronauts’ abilities to modulate both burst areas and frequencies during apnoea were sharply diminished.Spaceflight triggers long‐term neuroplastic changes reflected by reciptocal sympathetic and vagal motoneurone responsiveness to breathing changes. Abstract We studied six healthy astronauts five times, on Earth, in space on the first and 12th or 13th day of the 16 day Neurolab Space Shuttle mission, on landing day, and 5–6 days later. Astronauts followed a fixed protocol comprising controlled and random frequency breathing and apnoea, conceived to perturb their autonomic function and identify changes, if any, provoked by microgravity exposure. We recorded the electrocardiogram, finger photoplethysmographic arterial pressure, tidal carbon dioxide concentrations and volumes, and peroneal nerve muscle sympathetic activity on Earth (in the supine position) and in space. (Sympathetic nerve recordings were made during three sessions: preflight, late mission and landing day.) Arterial pressure changed systematically from preflight levels: pressure fell during early microgravity exposure, rose as microgravity exposure continued, and drifted back to preflight levels after return to Earth. Vagal metrics changed in opposite directions: vagal baroreflex gain and two indices of vagal fluctuations (root mean square of successive normal R‐R intervals; and proportion of successive normal R‐R intervals greater than 50 ms, divided by the total number of normal R‐R intervals) rose significantly during early microgravity exposure, fell as microgravity exposure continued, and descended to preflight levels upon return to Earth. Sympathetic mechanisms also changed. Burst frequencies (but not areas) during fixed frequency breathing were greater than preflight in space and on landing day, but their control during apnoea was sharply altered: astronauts increased their burst frequencies from already high levels, but they could not modulate either burst areas or frequencies appropriately. Space travel provokes long‐lasting sympathetic and vagal neuroplastic changes in healthy humans. PMID:27029027

Images in electroconvulsive therapy: ECS dose-dependently increases cell proliferation in the subgranular region of the rat hippocampus.

PubMed

Smitha, Jangama S M; Roopa, Ravindranath; Sagar, B K Chandrasekhar; Kutty, Bindu M; Andrade, Chittaranjan

2014-09-01

Stress and depression are associated with impaired neuroplasticity in the hippocampus; there is a decrease in neurogenesis, which is hypothesized to decrease the adaptative competence of the organism. Representative light microscopy images are presented which show that 6 once-daily electroconvulsive shocks (ECS), dose-dependently increased new cell formation in the subgranular region of the hippocampus in healthy adult male Wistar rats (10 sections per rat, 3 rats in each of sham ECS, 10 mC, and 40 mC groups). These neuroplasticity changes, demonstrated 1 month after the last ECS, may explain a part of the mechanism of action of electroconvulsive therapy in conditions such as depression.

Capturing neuroplastic changes after bimanual intensive rehabilitation in children with unilateral spastic cerebral palsy: A combined DTI, TMS and fMRI pilot study

PubMed Central

Bleyenheuft, Yannick; Dricot, Laurence; Gilis, Nathalie; Kuo, Hsing-Ching; Grandin, Cécile; Bleyenheuft, Corinne; Gordon, Andrew M.; Friel, Kathleen M.

2016-01-01

Intensive rehabilitation interventions have been shown to be efficacious in improving upper extremity function in children with unilateral spastic cerebral palsy (USCP). These interventions are based on motor learning principles and engage children in skillful movements. Improvements in upper extremity function are believed to be associated with neuroplastic changes. However, these neuroplastic changes have not been well-described in children with cerebral palsy, likely due to challenges in defining and implementing the optimal tools and tests in children. Here we documented the implementation of three different neurological assessments (diffusion tensor imaging-DTI, transcranial magnetic stimulation-TMS and functional magnetic resonance imaging-fMRI) before and after a bimanual intensive treatment (HABIT-ILE) in two children with USCP presenting differential corticospinal developmental reorganization (ipsilateral and contralateral). The aim of the study was to capture neurophysiological changes and to document the complementary relationship between these measures, the potential measurable changes and the feasibility of applying these techniques in children with USCP. Independent of cortical reorganization, both children showed increases in activation and size of the motor areas controlling the affected hand, quantified with different techniques. In addition, fMRI provided additional unexpected changes in the reward circuit while using the affected hand. PMID:26183338

Influence of different estrogens on neuroplasticity and cognition in the hippocampus.

PubMed

Barha, Cindy K; Galea, Liisa A M

2010-10-01

Estrogens modulate the morphology and function of the hippocampus. Recent studies have focused on the effects of different types of estrogens on neuroplasticity in the hippocampus and cognition. There are three main forms of estrogens found in mammals: estradiol, estrone, and estriol. The vast majority of studies have used estradiol to investigate the effects of estrogens on the brain. This review focuses on the effects of different estrogens on adult hippocampal neurogenesis, synaptic plasticity in the hippocampus, and cognition in female rats. Different forms of estrogens modulate neuroplasticity and cognition in complex and intriguing ways. Specifically, estrogens upregulate adult hippocampal neurogenesis (via cell proliferation) and synaptic protein levels in the hippocampus in a time- and dose-dependent manner. Low levels of estradiol facilitate spatial working memory and contextual fear conditioning while high levels of estradiol impair spatial working, spatial reference memory and contextual fear conditioning. In addition, estrone impairs contextual fear conditioning. Advances in our knowledge of how estrogens exert their effects on the brain may ultimately lead to refinements in targeted therapies for cognitive impairments at all stages of life. However caution should be taken in interpreting current research and in conducting future studies as estrogens likely work differently in males than in females. Copyright © 2010 Elsevier B.V. All rights reserved.

New Treatment Strategies of Depression: Based on Mechanisms Related to Neuroplasticity

PubMed Central

Lane, Hsien-Yuan

2017-01-01

Major depressive disorder is a severe and complex mental disorder. Impaired neurotransmission and disrupted signalling pathways may influence neuroplasticity, which is involved in the brain dysfunction in depression. Traditional neurobiological theories of depression, such as monoamine hypothesis, cannot fully explain the whole picture of depressive disorders. In this review, we discussed new treatment directions of depression, including modulation of glutamatergic system and noninvasive brain stimulation. Dysfunction of glutamatergic neurotransmission plays an important role in the pathophysiology of depression. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has rapid and lasting antidepressive effects in previous studies. In addition to ketamine, other glutamatergic modulators, such as sarcosine, also show potential antidepressant effect in animal models or clinical trials. Noninvasive brain stimulation is another new treatment strategy beyond pharmacotherapy. Growing evidence has demonstrated that superficial brain stimulations, such as transcranial magnetic stimulation, transcranial direct current stimulation, cranial electrotherapy stimulation, and magnetic seizure therapy, can improve depressive symptoms. The antidepressive effect of these brain stimulations may be through modulating neuroplasticity. In conclusion, drugs that modulate neurotransmission via NMDA receptor and noninvasive brain stimulation may provide new directions of treatment for depression. Furthermore, exploring the underlying mechanisms will help in developing novel therapies for depression in the future. PMID:28491480

Computational models and motor learning paradigms: Could they provide insights for neuroplasticity after stroke? An overview.

PubMed

Kiper, Pawel; Szczudlik, Andrzej; Venneri, Annalena; Stozek, Joanna; Luque-Moreno, Carlos; Opara, Jozef; Baba, Alfonc; Agostini, Michela; Turolla, Andrea

2016-10-15

Computational approaches for modelling the central nervous system (CNS) aim to develop theories on processes occurring in the brain that allow the transformation of all information needed for the execution of motor acts. Computational models have been proposed in several fields, to interpret not only the CNS functioning, but also its efferent behaviour. Computational model theories can provide insights into neuromuscular and brain function allowing us to reach a deeper understanding of neuroplasticity. Neuroplasticity is the process occurring in the CNS that is able to permanently change both structure and function due to interaction with the external environment. To understand such a complex process several paradigms related to motor learning and computational modeling have been put forward. These paradigms have been explained through several internal model concepts, and supported by neurophysiological and neuroimaging studies. Therefore, it has been possible to make theories about the basis of different learning paradigms according to known computational models. Here we review the computational models and motor learning paradigms used to describe the CNS and neuromuscular functions, as well as their role in the recovery process. These theories have the potential to provide a way to rigorously explain all the potential of CNS learning, providing a basis for future clinical studies. Copyright © 2016 Elsevier B.V. All rights reserved.

Brain volumetric and metabolic correlates of electroconvulsive therapy for treatment-resistant depression: a longitudinal neuroimaging study

PubMed Central

Cano, M; Martínez-Zalacaín, I; Bernabéu-Sanz, Á; Contreras-Rodríguez, O; Hernández-Ribas, R; Via, E; de Arriba-Arnau, A; Gálvez, V; Urretavizcaya, M; Pujol, J; Menchón, J M; Cardoner, N; Soriano-Mas, C

2017-01-01

Recent research suggests that neuroplastic and neuroinflammatory changes may account for the mode of action of electroconvulsive therapy (ECT), although extant data do not allow for a clear disambiguation between these two hypotheses. Multimodal neuroimaging approaches (for example, combining structural and metabolic information) may help in clarifying this issue. Here we aimed to assess longitudinal changes in (i) regional gray matter (GM) volumes and (ii) hippocampal metabolite concentrations throughout an acute course of bitemporal ECT, as well as (iii) to determine the association between imaging changes and clinical improvement. We assessed 12 patients with treatment-resistant depression (TRD) at four time points (pre-treatment, after the first ECT session, after the ninth ECT session and 15 days after ECT course completion) and 10 healthy participants at two time points, 5 weeks apart. Patients with TRD showed bilateral medial temporal lobe (MTL) and perigenual anterior cingulate cortex volume increases. Left MTL volume increase was associated with (i) a hippocampal N-acetylaspartate concentration decrease, (ii) a hippocampal Glutamate+Glutamine concentration increase and (iii) significant clinical improvement. The observed findings are, in part, compatible with both neuroplastic and neuroinflammatory changes induced by ECT. We postulate that such phenomena may be interrelated, therefore reconciling the neuroplasticity and neuroinflammatory hypotheses of ECT action. PMID:28170003

Four birds with one stone? Reparative, neuroplastic, cardiorespiratory, and metabolic benefits of aerobic exercise poststroke.

PubMed

Ploughman, Michelle; Kelly, Liam P

2016-12-01

Converging evidence from animal models of stroke and clinical trials suggests that aerobic exercise has effects across multiple targets. The subacute phase is characterized by a period of heightened neuroplasticity when aerobic exercise has the potential to optimize recovery. In animals, low intensity aerobic exercise shrinks lesion size and reduces cell death and inflammation, beginning 24 h poststroke. Also in animals, aerobic exercise upregulates brain-derived neurotrophic factor near the lesion and improves learning. In terms of neuroplastic effects, clinical trial results are less convincing and have only examined effects in chronic stroke. Stroke patients demonstrate cardiorespiratory fitness levels below the threshold required to carry out daily activities. This may contribute to a 'neurorehabilitation ceiling' that limits capacity to practice at a high enough frequency and intensity to promote recovery. Aerobic exercise when delivered 2-5 days per week at moderate to high intensity beginning as early as 5 days poststroke improves cardiorespiratory fitness, dyslipidemia, and glucose tolerance. Based on the evidence discussed and applying principles of periodization commonly used to prepare athletes for competition, we have created a model of aerobic training in subacute stroke in which training is delivered in density blocks (duration × intensity) matched to recovery phases.

Enhanced Neuroplasticity by the Metabolic Enhancer Piracetam Associated with Improved Mitochondrial Dynamics and Altered Permeability Transition Pore Function.

PubMed

Stockburger, Carola; Miano, Davide; Pallas, Thea; Friedland, Kristina; Müller, Walter E

2016-01-01

The mitochondrial cascade hypothesis of dementia assumes mitochondrial dysfunction leading to reduced energy supply, impaired neuroplasticity, and finally cell death as one major pathomechanism underlying the continuum from brain aging over mild cognitive impairment to initial and advanced late onset Alzheimer's disease. Accordingly, improving mitochondrial function has become an important strategy to treat the early stages of this continuum. The metabolic enhancer piracetam has been proposed as possible prototype for those compounds by increasing impaired mitochondrial function and related aspects like mechanisms of neuroplasticity. We here report that piracetam at therapeutically relevant concentrations improves neuritogenesis in the human cell line SH-SY5Y over conditions mirroring the whole spectrum of age-associated cognitive decline. These effects go parallel with improvement of impaired mitochondrial dynamics shifting back fission and fusion balance to the energetically more favorable fusion site. Impaired fission and fusion balance can also be induced by a reduction of the mitochondrial permeability transition pore (mPTP) function as atractyloside which indicates the mPTP has similar effects on mitochondrial dynamics. These changes are also reduced by piracetam. These findings suggest the mPTP as an important target for the beneficial effects of piracetam on mitochondrial function.

Enhanced Neuroplasticity by the Metabolic Enhancer Piracetam Associated with Improved Mitochondrial Dynamics and Altered Permeability Transition Pore Function

PubMed Central

Stockburger, Carola; Miano, Davide; Pallas, Thea; Müller, Walter E.

2016-01-01

The mitochondrial cascade hypothesis of dementia assumes mitochondrial dysfunction leading to reduced energy supply, impaired neuroplasticity, and finally cell death as one major pathomechanism underlying the continuum from brain aging over mild cognitive impairment to initial and advanced late onset Alzheimer's disease. Accordingly, improving mitochondrial function has become an important strategy to treat the early stages of this continuum. The metabolic enhancer piracetam has been proposed as possible prototype for those compounds by increasing impaired mitochondrial function and related aspects like mechanisms of neuroplasticity. We here report that piracetam at therapeutically relevant concentrations improves neuritogenesis in the human cell line SH-SY5Y over conditions mirroring the whole spectrum of age-associated cognitive decline. These effects go parallel with improvement of impaired mitochondrial dynamics shifting back fission and fusion balance to the energetically more favorable fusion site. Impaired fission and fusion balance can also be induced by a reduction of the mitochondrial permeability transition pore (mPTP) function as atractyloside which indicates the mPTP has similar effects on mitochondrial dynamics. These changes are also reduced by piracetam. These findings suggest the mPTP as an important target for the beneficial effects of piracetam on mitochondrial function. PMID:27747106

Neuroplasticity Changes on Human Motor Cortex Induced by Acupuncture Therapy: A Preliminary Study.

PubMed

Yang, Yi; Eisner, Ines; Chen, Siqi; Wang, Shaosong; Zhang, Fan; Wang, Linpeng

2017-01-01

While neuroplasticity changes measured by transcranial magnetic stimulation have been proved to be highly correlated to motor recovery and have been tested in various forms of interventions, it has not been applied to investigate the neurophysiologic mechanism of acupuncture therapy. The aim of this study is to investigate neuroplasticity changes induced by a single session of acupuncture therapy in healthy adults, regarding the excitability change on bilateral primary motor cortex and interhemispheric inhibition. Ten subjects took a 30-minute acupuncture therapy and the same length relaxing phase in separate days. Transcranial magnetic stimulation measures, including resting motor threshold, amplitudes of motor-evoked potential, and interhemispheric inhibition, were assessed before and 10 minutes after intervention. Acupuncture treatment showed significant changes on potential amplitude from both ipsilateral and contralateral hemispheres to acupuncture compared to baseline. Also, interhemispheric inhibition from the contralateral motor cortex to the opposite showed a significant decline. The results indicated that corticomotoneuronal excitability and interhemispheric competition could be modulated by acupuncture therapy on healthy subjects. The following question about whether these changes will be observed in the same way on stroke patients and whether they correlate with the therapeutic effect on movement need to be answered by following studies. This trial is registered with ISRCTN13074245.

Neuroplasticity Changes on Human Motor Cortex Induced by Acupuncture Therapy: A Preliminary Study

PubMed Central

Eisner, Ines; Chen, Siqi; Wang, Shaosong; Zhang, Fan

2017-01-01

While neuroplasticity changes measured by transcranial magnetic stimulation have been proved to be highly correlated to motor recovery and have been tested in various forms of interventions, it has not been applied to investigate the neurophysiologic mechanism of acupuncture therapy. The aim of this study is to investigate neuroplasticity changes induced by a single session of acupuncture therapy in healthy adults, regarding the excitability change on bilateral primary motor cortex and interhemispheric inhibition. Ten subjects took a 30-minute acupuncture therapy and the same length relaxing phase in separate days. Transcranial magnetic stimulation measures, including resting motor threshold, amplitudes of motor-evoked potential, and interhemispheric inhibition, were assessed before and 10 minutes after intervention. Acupuncture treatment showed significant changes on potential amplitude from both ipsilateral and contralateral hemispheres to acupuncture compared to baseline. Also, interhemispheric inhibition from the contralateral motor cortex to the opposite showed a significant decline. The results indicated that corticomotoneuronal excitability and interhemispheric competition could be modulated by acupuncture therapy on healthy subjects. The following question about whether these changes will be observed in the same way on stroke patients and whether they correlate with the therapeutic effect on movement need to be answered by following studies. This trial is registered with ISRCTN13074245. PMID:28293438

Structural Brain Correlates Associated with Professional Handball Playing

PubMed Central

Hänggi, Jürgen; Langer, Nicolas; Lutz, Kai; Birrer, Karin; Mérillat, Susan; Jäncke, Lutz

2015-01-01

Background There is no doubt that good bimanual performance is very important for skilled handball playing. The control of the non-dominant hand is especially demanding since efficient catching and throwing needs both hands. Methodology/Hypotheses We investigated training-induced structural neuroplasticity in professional handball players using several structural neuroimaging techniques and analytic approaches and also provide a review of the literature about sport-induced structural neuroplastic alterations. Structural brain adaptations were expected in regions relevant for motor and somatosensory processing such as the grey matter (GM) of the primary/secondary motor (MI/supplementary motor area, SMA) and somatosensory cortex (SI/SII), basal ganglia, thalamus, and cerebellum and in the white matter (WM) of the corticospinal tract (CST) and corpus callosum, stronger in brain regions controlling the non-dominant left hand. Results Increased GM volume in handball players compared with control subjects were found in the right MI/SI, bilateral SMA/cingulate motor area, and left intraparietal sulcus. Fractional anisotropy (FA) and axial diffusivity were increased within the right CST in handball players compared with control women. Age of handball training commencement correlated inversely with GM volume in the right and left MI/SI and years of handball training experience correlated inversely with radial diffusivity in the right CST. Subcortical structures tended to be larger in handball players. The anatomical measures of the brain regions associated with handball playing were positively correlated in handball players, but not interrelated in control women. Discussion/Conclusion Training-induced structural alterations were found in the somatosensory-motor network of handball players, more pronounced in the right hemisphere controlling the non-dominant left hand. Correlations between handball training-related measures and anatomical differences suggest neuroplastic adaptations rather than a genetic predisposition for a ball playing affinity. Investigations of neuroplasticity specifically in sportsmen might help to understand the neural mechanisms of expertise in general. PMID:25915906

Melatonin improves neuroplasticity by upregulating the growth-associated protein-43 (GAP-43) and NMDAR postsynaptic density-95 (PSD-95) proteins in cultured neurons exposed to glutamate excitotoxicity and in rats subjected to transient focal cerebral ischemia even during a long-term recovery period.

PubMed

Juan, Wei-Sheng; Huang, Sheng-Yang; Chang, Che-Chao; Hung, Yu-Chang; Lin, Yu-Wen; Chen, Tsung-Ying; Lee, Ai-Hua; Lee, Ai-Chiang; Wu, Tian-Shung; Lee, E-Jian

2014-03-01

Recent evidence shows that the NMDAR postsynaptic density-95 (PSD-95), growth-associated protein-43 (GAP-43), and matrix metalloproteinase-9 (MMP-9) protein enhance neuroplasticity at the subacute stage of stroke. Here, we evaluated whether melatonin would modulate the PSD-95, GAP-43, and MMP-9 proteins in cultured neurons exposed to glutamate excitotoxicity and in rats subjected to experimental stroke. Adult male Sprague-Dawley rats were treated with melatonin (5 mg/kg) or vehicle at reperfusion onset after transient occlusion of the right middle cerebral artery (tMCAO) for 90 min. Animals were euthanized for Western immunoblot analyses for the PSD-95 and GAP-43 proteins and gelatin zymography for the MMP-9 activity at 7 days postinsult. Another set of animals was sacrificed for histologic and Golgi-Cox-impregnated sections at 28 days postinsult. In cultured neurons exposed to glutamate excitotoxicity, melatonin significantly upregulated the GAP-43 and PSD-95 expressions and improved dendritic aborizations (P<0.05, respectively). Relative to controls, melatonin-treated stroke animals caused a significant improvement in GAP-43 and PSD-95 expressions as well as the MMP-9 activity in the ischemic brain (P<0.05). Consequently, melatonin also significantly promoted the dendritic spine density and reduced infarction in the ischemic brain, and improved neurobehaviors as well at 28 days postinsult (P<0.05, respectively). Together, melatonin upregulates GAP-43, PSD-95, and MMP-9 proteins, which likely accounts for its actions to improve neuroplasticity in cultured neurons exposed to glutamate excitotoxicity and to enhance long-term neuroprotection, neuroplasticity, and brain remodeling in stroke rats. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Circuits Regulating Pleasure and Happiness-Mechanisms of Depression.

PubMed

Loonen, Anton J M; Ivanova, Svetlana A

2016-01-01

According to our model of the regulation of appetitive-searching vs. distress-avoiding behaviors, the motivation to display these essential conducts is regulated by two parallel cortico-striato-thalamo-cortical, re-entry circuits, including the core and the shell parts of the nucleus accumbens, respectively. An entire series of basal ganglia, running from the caudate nucleus on one side, to the centromedial amygdala on the other side, controls the intensity of these reward-seeking and misery-fleeing behaviors by stimulating the activity of the (pre)frontal and limbic cortices. Hyperactive motivation to display behavior that potentially results in reward induces feelings of hankering (relief leads to pleasure). Hyperactive motivation to exhibit behavior related to avoidance of misery results in dysphoria (relief leads to happiness). These two systems collaborate in a reciprocal fashion. In clinical depression, a mismatch exists between the activities of these two circuits: the balance is shifted to the misery-avoiding side. Five theories have been developed to explain the mechanism of depressive mood disorders, including the monoamine, biorhythm, neuro-endocrine, neuro-immune, and kindling/neuroplasticity theories. This paper describes these theories in relationship to the model (described above) of the regulation of reward-seeking vs. misery-avoiding behaviors. Chronic stress that leads to structural changes may induce the mismatch between the two systems. This mismatch leads to lack of pleasure, low energy, and indecisiveness, on one hand, and dysphoria, continuous worrying, and negative expectations on the other hand. The neuroplastic effects of monoamines, cortisol, and cytokines may mediate the induction of these structural alterations. Long-term exposure to stressful situations (particularly experienced during childhood) may lead to increased susceptibility for developing this condition. This hypothesis opens up the possibility of treating depression with psychotherapy. Genetic and other biological factors (toxic, infectious, or traumatic) may increase sensitivity to the induction of relevant neuroplastic changes. Reversal or compensation of these neuroplastic adjustments may explain the effects of biological therapies in treating depression.

Circuits Regulating Pleasure and Happiness—Mechanisms of Depression

PubMed Central

Loonen, Anton J. M.; Ivanova, Svetlana A.

2016-01-01

According to our model of the regulation of appetitive-searching vs. distress-avoiding behaviors, the motivation to display these essential conducts is regulated by two parallel cortico-striato-thalamo-cortical, re-entry circuits, including the core and the shell parts of the nucleus accumbens, respectively. An entire series of basal ganglia, running from the caudate nucleus on one side, to the centromedial amygdala on the other side, controls the intensity of these reward-seeking and misery-fleeing behaviors by stimulating the activity of the (pre)frontal and limbic cortices. Hyperactive motivation to display behavior that potentially results in reward induces feelings of hankering (relief leads to pleasure). Hyperactive motivation to exhibit behavior related to avoidance of misery results in dysphoria (relief leads to happiness). These two systems collaborate in a reciprocal fashion. In clinical depression, a mismatch exists between the activities of these two circuits: the balance is shifted to the misery-avoiding side. Five theories have been developed to explain the mechanism of depressive mood disorders, including the monoamine, biorhythm, neuro-endocrine, neuro-immune, and kindling/neuroplasticity theories. This paper describes these theories in relationship to the model (described above) of the regulation of reward-seeking vs. misery-avoiding behaviors. Chronic stress that leads to structural changes may induce the mismatch between the two systems. This mismatch leads to lack of pleasure, low energy, and indecisiveness, on one hand, and dysphoria, continuous worrying, and negative expectations on the other hand. The neuroplastic effects of monoamines, cortisol, and cytokines may mediate the induction of these structural alterations. Long-term exposure to stressful situations (particularly experienced during childhood) may lead to increased susceptibility for developing this condition. This hypothesis opens up the possibility of treating depression with psychotherapy. Genetic and other biological factors (toxic, infectious, or traumatic) may increase sensitivity to the induction of relevant neuroplastic changes. Reversal or compensation of these neuroplastic adjustments may explain the effects of biological therapies in treating depression. PMID:27891086

Post-stroke balance rehabilitation under multi-level electrotherapy: a conceptual review

PubMed Central

Dutta, Anirban; Lahiri, Uttama; Das, Abhijit; Nitsche, Michael A.; Guiraud, David

2014-01-01

Stroke is caused when an artery carrying blood from heart to an area in the brain bursts or a clot obstructs the blood flow thereby preventing delivery of oxygen and nutrients. About half of the stroke survivors are left with some degree of disability. Innovative methodologies for restorative neurorehabilitation are urgently required to reduce long-term disability. The ability of the nervous system to respond to intrinsic or extrinsic stimuli by reorganizing its structure, function, and connections is called neuroplasticity. Neuroplasticity is involved in post-stroke functional disturbances, but also in rehabilitation. It has been shown that active cortical participation in a closed-loop brain machine interface (BMI) can induce neuroplasticity in cortical networks where the brain acts as a controller, e.g., during a visuomotor task. Here, the motor task can be assisted with neuromuscular electrical stimulation (NMES) where the BMI will act as a real-time decoder. However, the cortical control and induction of neuroplasticity in a closed-loop BMI is also dependent on the state of brain, e.g., visuospatial attention during visuomotor task performance. In fact, spatial neglect is a hidden disability that is a common complication of stroke and is associated with prolonged hospital stays, accidents, falls, safety problems, and chronic functional disability. This hypothesis and theory article presents a multi-level electrotherapy paradigm toward motor rehabilitation in virtual reality that postulates that while the brain acts as a controller in a closed-loop BMI to drive NMES, the state of brain can be can be altered toward improvement of visuomotor task performance with non-invasive brain stimulation (NIBS). This leads to a multi-level electrotherapy paradigm where a virtual reality-based adaptive response technology is proposed for post-stroke balance rehabilitation. In this article, we present a conceptual review of the related experimental findings. PMID:25565937

A Single Bolus of Docosahexaenoic Acid Promotes Neuroplastic Changes in the Innervation of Spinal Cord Interneurons and Motor Neurons and Improves Functional Recovery after Spinal Cord Injury.

PubMed

Liu, Zhuo-Hao; Yip, Ping K; Adams, Louise; Davies, Meirion; Lee, Jae Won; Michael, Gregory J; Priestley, John V; Michael-Titus, Adina T

2015-09-16

Docosahexaenoic acid (DHA) is an ω-3 polyunsaturated fatty acid that is essential in brain development and has structural and signaling roles. Acute DHA administration is neuroprotective and promotes functional recovery in animal models of adult spinal cord injury (SCI). However, the mechanisms underlying this recovery have not been fully characterized. Here we investigated the effects of an acute intravenous bolus of DHA delivered after SCI and characterized DHA-induced neuroplasticity within the adult injured spinal cord. We found robust sprouting of uninjured corticospinal and serotonergic fibers in a rat cervical hemisection SCI model. A mouse pyramidotomy model was used to confirm that this robust sprouting was not species or injury model specific. Furthermore, we demonstrated that corticospinal fibers sprouting to the denervated side of the cord following pyramidotomy contact V2a interneurons. We also demonstrated increased serotonin fibers and synaptophysin in direct contact with motor neurons. DHA also increased synaptophysin in rat cortical cell cultures. A reduction in phosphatase and tensin homolog (PTEN) has been shown to be involved in axonal regeneration and synaptic plasticity. We showed that DHA significantly upregulates miR-21 and downregulates PTEN in corticospinal neurons. Downregulation of PTEN and upregulation of phosphorylated AKT by DHA were also seen in primary cortical neuron cultures and were accompanied by increased neurite outgrowth. In summary, acute DHA induces anatomical and synaptic plasticity in adult injured spinal cord. This study shows that DHA has therapeutic potential in cervical SCI and provides evidence that DHA could exert its beneficial effects in SCI via enhancement of neuroplasticity. In this study, we show that an acute intravenous injection of docosahexaenoic acid (DHA) 30 min after spinal cord injury induces neuroplasticity. We found robust sprouting of uninjured corticospinal and serotonergic fibers in a rat hemisection spinal cord injury model. A mouse pyramidotomy model was used to confirm that the robust sprouting involved V2a interneurons. We show that DHA significantly upregulates miR-21 and phosphorylated AKT, and downregulates phosphatase and tensin homolog (PTEN), which is involved in suppressing anatomical plasticity, in corticospinal neurons and in primary cortical neuron cultures. We conclude that acute DHA can induce anatomical and synaptic plasticity. This provides direct evidence that DHA could exert its beneficial effects in spinal cord injury via neuroplasticity enhancement. Copyright © 2015 the authors 0270-6474/15/3512734-20$15.00/0.

Conscience and Consciousness: a definition

PubMed Central

Vithoulkas, G; Muresanu, DF

2014-01-01

While consciousness has been examined extensively in its different aspects, like in philosophy, psychiatry, neurophysiology, neuroplasticity, etc., conscience though it is an equal important aspect of the human existence, which remains an unknown to a great degree as an almost transcendental aspect of the human mind. It has not been examined as thoroughly as consciousness and largely remains a “terra incognita" for its neurophysiology, brain topography, etc. Conscience and consciousness are part of a system of information that governs our experience and decision making process. The intent of this paper is to define these terms, to discuss about consciousness from both neurological and quantum physics point of view, the relationship between the dynamics of consciousness and neuroplasticity and to highlight the relationship between conscience, stress and health. PMID:24653768

Retraction: Borroto-Escuela et al., The existence of FGFR1-5-HT1A receptor heterocomplexes in midbrain 5-HT neurons of the rat: relevance for neuroplasticity.

PubMed

2013-07-10

The Journal of Neuroscience has received a report describing an investigation by the Karolinska Institutet, which found substantial data misrepresentation in the article "The Existence of FGFR1-5-HT1A Receptor Heterocomplexes in Midbrain 5-HT Neurons of the Rat: Relevance for Neuroplasticity" by Dasiel O. Borroto-Escuela, Wilber Romero-Fernandez, Mileidys Pérez-Alea, Manuel Narvaez, Alexander O. Tarakanov, Giuseppa Mudó , Luigi F. Agnati, Francisco Ciruela, Natale Belluardo, and Kjell Fuxe, which appeared on pages 6295-6303 of the May 2, 2012 issue. Because the results cannot be considered reliable, the editors of The Journal are retracting the paper.

Conscience and consciousness: a definition.

PubMed

Vithoulkas, G; Muresanu, D F

2014-03-15

While consciousness has been examined extensively in its different aspects, like in philosophy, psychiatry, neurophysiology, neuroplasticity, etc., conscience though it is an equal important aspect of the human existence, which remains an unknown to a great degree as an almost transcendental aspect of the human mind. It has not been examined as thoroughly as consciousness and largely remains a "terra incognita" for its neurophysiology, brain topography, etc. Conscience and consciousness are part of a system of information that governs our experience and decision making process. The intent of this paper is to define these terms, to discuss about consciousness from both neurological and quantum physics point of view, the relationship between the dynamics of consciousness and neuroplasticity and to highlight the relationship between conscience, stress and health.

Untangling nociceptive, neuropathic and neuroplastic mechanisms underlying the biological domain of back pain.

PubMed

Hush, Julia M; Stanton, Tasha R; Siddall, Philip; Marcuzzi, Anna; Attal, Nadine

2013-05-01

SUMMARY Current clinical practice guidelines advocate a model of diagnostic triage for back pain, underpinned by the biopsychosocial paradigm. However, limitations of this clinical model have become apparent: it can be difficult to classify patients into the diagnostic triage categories; patients with 'nonspecific back pain' are clearly not a homogenous group; and mean effects of treatments based on this approach are small. In this article, it is proposed that the biological domain of the biopsychosocial model needs to be reconceptualized using a neurobiological mechanism-based approach. Recent evidence about nociceptive and neuropathic contributors to back pain is outlined in the context of maladaptive neuroplastic changes of the somatosensory system. Implications for clinical practice and research are discussed.

Respiratory neuroplasticity - Overview, significance and future directions.

PubMed

Fuller, David D; Mitchell, Gordon S

2017-01-01

Neuroplasticity is an important property of the neural system controlling breathing. However, our appreciation for its importance is still relatively new, and we have much to learn concerning different forms of plasticity, their underlying mechanisms, and their biological and clinical significance. In this brief review, we discuss several well-studied models of respiratory plasticity, including plasticity initiated by inactivity in the respiratory system, intermittent and sustained hypoxia, and traumatic injury to the spinal cord. Other aspects of respiratory plasticity are considered in other contributions to this special edition of Experimental Neurology on respiratory plasticity. Finally, we conclude with discussions concerning the biological and clinical significance of respiratory motor plasticity, and areas in need of future research effort. Copyright © 2016. Published by Elsevier Inc.

The effect of leisure activity golf practice on motor imagery: an fMRI study in middle adulthood

PubMed Central

Bezzola, Ladina; Mérillat, Susan; Jäncke, Lutz

2012-01-01

Much is known about practice-induced plasticity of the motor system. But it is not clear how a physical training influences the mental rehearsal of the practiced task and its associated hemodynamic responses. In the present longitudinal study with two measurement time-points, we used the method of functional magnetic resonance imaging (fMRI) and a motor imagery task, in order to explore the dynamic neuro-functional changes induced by a highly complex physical training. The 11 golf novices between the age of 40 and 60 years practiced the motor training as leisure activity. Additionally, data from an age and sex-matched control group without golf training was collected. As a main result, we demonstrate that changes between the two measurement time-points were only found in the golf novice group. The golf novices showed a decrease in hemodynamic responses during the mental rehearsal of the golf swing in non-primary motor areas after the 40 h of golf practice. Thus, the results indicate that a complex physical leisure activity induces functional neuroplasticity in the seldom studied population of middle-aged adults, and that this effect is evident during mental rehearsal of the practiced task. This finding supports the idea that (a) a skill improvement is associated with a modified activation pattern in the associated neuronal network that can be identified during mental rehearsal of the practiced task, and that (b) a strict training protocol is not necessary to induce functional neuroplasticity. PMID:22479243

Respiratory modulation of human autonomic function: long-term neuroplasticity in space.

PubMed

Eckberg, Dwain L; Diedrich, André; Cooke, William H; Biaggioni, Italo; Buckey, Jay C; Pawelczyk, James A; Ertl, Andrew C; Cox, James F; Kuusela, Tom A; Tahvanainen, Kari U O; Mano, Tadaaki; Iwase, Satoshi; Baisch, Friedhelm J; Levine, Benjamin D; Adams-Huet, Beverley; Robertson, David; Blomqvist, C Gunnar

2016-10-01

We studied healthy astronauts before, during and after the Neurolab Space Shuttle mission with controlled breathing and apnoea, to identify autonomic changes that might contribute to postflight orthostatic intolerance. Measurements included the electrocardiogram, finger photoplethysmographic arterial pressure, respiratory carbon dioxide levels, tidal volume and peroneal nerve muscle sympathetic activity. Arterial pressure fell and then rose in space, and drifted back to preflight levels after return to Earth. Vagal metrics changed in opposite directions: vagal baroreflex gain and two indices of vagal fluctuations rose and then fell in space, and descended to preflight levels upon return to Earth. Sympathetic burst frequencies (but not areas) were greater than preflight in space and on landing day, and astronauts' abilities to modulate both burst areas and frequencies during apnoea were sharply diminished. Spaceflight triggers long-term neuroplastic changes reflected by reciptocal sympathetic and vagal motoneurone responsiveness to breathing changes. We studied six healthy astronauts five times, on Earth, in space on the first and 12th or 13th day of the 16 day Neurolab Space Shuttle mission, on landing day, and 5-6 days later. Astronauts followed a fixed protocol comprising controlled and random frequency breathing and apnoea, conceived to perturb their autonomic function and identify changes, if any, provoked by microgravity exposure. We recorded the electrocardiogram, finger photoplethysmographic arterial pressure, tidal carbon dioxide concentrations and volumes, and peroneal nerve muscle sympathetic activity on Earth (in the supine position) and in space. (Sympathetic nerve recordings were made during three sessions: preflight, late mission and landing day.) Arterial pressure changed systematically from preflight levels: pressure fell during early microgravity exposure, rose as microgravity exposure continued, and drifted back to preflight levels after return to Earth. Vagal metrics changed in opposite directions: vagal baroreflex gain and two indices of vagal fluctuations (root mean square of successive normal R-R intervals; and proportion of successive normal R-R intervals greater than 50 ms, divided by the total number of normal R-R intervals) rose significantly during early microgravity exposure, fell as microgravity exposure continued, and descended to preflight levels upon return to Earth. Sympathetic mechanisms also changed. Burst frequencies (but not areas) during fixed frequency breathing were greater than preflight in space and on landing day, but their control during apnoea was sharply altered: astronauts increased their burst frequencies from already high levels, but they could not modulate either burst areas or frequencies appropriately. Space travel provokes long-lasting sympathetic and vagal neuroplastic changes in healthy humans. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Electrifying the motor engram: effects of tDCS on motor learning and control

PubMed Central

de Xivry, Jean-Jacques Orban; Shadmehr, Reza

2014-01-01

Learning to control our movements accompanies neuroplasticity of motor areas of the brain. The mechanisms of neuroplasticity are diverse and produce what is referred to as the motor engram, i.e. the neural trace of the motor memory. Transcranial direct current stimulation (tDCS) alters the neural and behavioral correlates of motor learning, but its precise influence on the motor engram is unknown. In this review, we summarize the effects of tDCS on neural activity and suggest a few key principles: 1) firing rates are increased by anodal polarization and decreased by cathodal polarization, 2) anodal polarization strengthens newly formed associations, and 3) polarization modulates the memory of new/preferred firing patterns. With these principles in mind, we review the effects of tDCS on motor control, motor learning, and clinical applications. The increased spontaneous and evoked firing rates may account for the modulation of dexterity in non-learning tasks by tDCS. The facilitation of new association may account for the effect of tDCS on learning in sequence tasks while the ability of tDCS to strengthen memories of new firing patterns may underlie the effect of tDCS on consolidation of skills. We then describe the mechanisms of neuroplasticity of motor cortical areas and how they might be influenced by tDCS. We end with current challenges for the fields of brain stimulation and motor learning. PMID:25200178

Brain Plasticity following Intensive Bimanual Therapy in Children with Hemiparesis: Preliminary Evidence

PubMed Central

Weinstein, Maya; Myers, Vicki; Green, Dido; Schertz, Mitchell; Shiran, Shelly I.; Geva, Ronny; Artzi, Moran; Gordon, Andrew M.; Fattal-Valevski, Aviva; Ben Bashat, Dafna

2015-01-01

Neuroplasticity studies examining children with hemiparesis (CH) have focused predominantly on unilateral interventions. CH also have bimanual coordination impairments with bimanual interventions showing benefits. We explored neuroplasticity following hand-arm bimanual intensive therapy (HABIT) of 60 hours in twelve CH (6 females, mean age 11 ± 3.6 y). Serial behavioral evaluations and MR imaging including diffusion tensor (DTI) and functional (fMRI) imaging were performed before, immediately after, and at 6-week follow-up. Manual skills were assessed repeatedly with the Assisting Hand Assessment, Children's Hand Experience Questionnaire, and Jebsen-Taylor Test of Hand Function. Beta values, indicating the level of activation, and lateralization index (LI), indicating the pattern of brain activation, were computed from fMRI. White matter integrity of major fibers was assessed using DTI. 11/12 children showed improvement after intervention in at least one measure, with 8/12 improving on two or more tests. Changes were retained in 6/8 children at follow-up. Beta activation in the affected hemisphere increased at follow-up, and LI increased both after intervention and at follow-up. Correlations between LI and motor function emerged after intervention. Increased white matter integrity was detected in the corpus callosum and corticospinal tract after intervention in about half of the participants. Results provide first evidence for neuroplasticity changes following bimanual intervention in CH. PMID:26640717

Consciousness, brain, neuroplasticity

PubMed Central

Askenasy, Jean; Lehmann, Joseph

2013-01-01

Subjectivity, intentionality, self-awareness and will are major components of consciousness in human beings. Changes in consciousness and its content following different brain processes and malfunction have long been studied. Cognitive sciences assume that brain activities have an infrastructure, but there is also evidence that consciousness itself may change this infrastructure. The two-way influence between brain and consciousness has been at the center of philosophy and less so, of science. This so-called bottom-up and top-down interrelationship is controversial and is the subject of our article. We would like to ask: how does it happen that consciousness may provoke structural changes in the brain? The living brain means continuous changes at the synaptic level with every new experience, with every new process of learning, memorizing or mastering new and existing skills. Synapses are generated and dissolved, while others are preserved, in an ever-changing process of so-called neuroplasticity. Ongoing processes of synaptic reinforcements and decay occur during wakefulness when consciousness is present, but also during sleep when it is mostly absent. We suggest that consciousness influences brain neuroplasticity both during wakefulness as well as sleep in a top-down way. This means that consciousness really activates synaptic flow and changes brain structures and functional organization. The dynamic impact of consciousness on brain never stops despite the relative stationary structure of the brain. Such a process can be a target for medical intervention, e.g., by cognitive training. PMID:23847580

Safety and improvement of movement function after stroke with atomoxetine: A pilot randomized trial

PubMed Central

Ward, Andrea; Carrico, Cheryl; Powell, Elizabeth; Westgate, Philip M.; Nichols, Laurie; Fleischer, Anne; Sawaki, Lumy

2016-01-01

Background: Intensive, task-oriented motor training has been associated with neuroplastic reorganization and improved upper extremity movement function after stroke. However, to optimize such training for people with moderate-to-severe movement impairment, pharmacological modulation of neuroplasticity may be needed as an adjuvant intervention. Objective: Evaluate safety, as well as improvement in movement function, associated with motor training paired with a drug to upregulate neuroplasticity after stroke. Methods: In this double-blind, randomized, placebo-controlled study, 12 subjects with chronic stroke received either atomoxetine or placebo paired with motor training. Safety was assessed using vital signs. Upper extremity movement function was assessed using Fugl-Meyer Assessment, Wolf Motor Function Test, and Action Research Arm Test at baseline, post-intervention, and 1-month follow-up. Results: No significant between-groups differences were found in mean heart rate (95% CI, –12.4–22.6; p = 0.23), mean systolic blood pressure (95% CI, –1.7–29.6; p = 0.21), or mean diastolic blood pressure (95% CI, –10.4–13.3; p = 0.08). A statistically significant between-groups difference on Fugl-Meyer at post-intervention favored the atomoxetine group (95% CI, 1.6–12.7; p = 0.016). Conclusion: Atomoxetine combined with motor training appears safe and may optimize motor training outcomes after stroke. PMID:27858723

Capturing neuroplastic changes after bimanual intensive rehabilitation in children with unilateral spastic cerebral palsy: A combined DTI, TMS and fMRI pilot study.

PubMed

Bleyenheuft, Yannick; Dricot, Laurence; Gilis, Nathalie; Kuo, Hsing-Ching; Grandin, Cécile; Bleyenheuft, Corinne; Gordon, Andrew M; Friel, Kathleen M

2015-01-01

Intensive rehabilitation interventions have been shown to be efficacious in improving upper extremity function in children with unilateral spastic cerebral palsy (USCP). These interventions are based on motor learning principles and engage children in skillful movements. Improvements in upper extremity function are believed to be associated with neuroplastic changes. However, these neuroplastic changes have not been well-described in children with cerebral palsy, likely due to challenges in defining and implementing the optimal tools and tests in children. Here we documented the implementation of three different neurological assessments (diffusion tensor imaging-DTI, transcranial magnetic stimulation-TMS and functional magnetic resonance imaging-fMRI) before and after a bimanual intensive treatment (HABIT-ILE) in two children with USCP presenting differential corticospinal developmental reorganization (ipsilateral and contralateral). The aim of the study was to capture neurophysiological changes and to document the complementary relationship between these measures, the potential measurable changes and the feasibility of applying these techniques in children with USCP. Independent of cortical reorganization, both children showed increases in activation and size of the motor areas controlling the affected hand, quantified with different techniques. In addition, fMRI provided additional unexpected changes in the reward circuit while using the affected hand. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Prolonged therapeutic hypothermia does not adversely impact neuroplasticity after global ischemia in rats

PubMed Central

Silasi, Gergely; Klahr, Ana C; Hackett, Mark J; Auriat, Angela M; Nichol, Helen; Colbourne, Frederick

2012-01-01

Hypothermia improves clinical outcome after cardiac arrest in adults. Animal data show that a day or more of cooling optimally reduces edema and tissue injury after cerebral ischemia, especially after longer intervention delays. Lengthy treatments, however, may inhibit repair processes (e.g., synaptogenesis). Thus, we evaluated whether unilateral brain hypothermia (∼33°C) affects neuroplasticity in the rat 2-vessel occlusion model. In the first experiment, we cooled starting 1 hour after ischemia for 2, 4, or 7 days. Another group was cooled for 2 days starting 48 hours after ischemia. One group remained normothermic throughout. All hypothermia treatments started 1 hour after ischemia equally reduced hippocampal CA1 injury in the cooled hemisphere compared with the normothermic side and the normothermic group. Cooling only on days 3 and 4 was not beneficial. Importantly, no treatment influenced neurogenesis (Ki67/Doublecortin (DCX) staining), synapse formation (synaptophysin), or brain-derived neurotropic factor (BDNF) immunohistochemistry. A second experiment confirmed that BDNF levels (ELISA) were equivalent in normothermic and 7-day cooled rats. Last, we measured zinc (Zn), which is important in plasticity, with X-ray fluorescence imaging in normothermic and 7-day cooled rats. Hypothermia did not alter the postischemic distribution of Zn within the hippocampus. In summary, cooling significantly mitigates injury without compromising neuroplasticity. PMID:22434072

Stress-induced neuroplasticity: (mal)adaptation to adverse life events in patients with PTSD--a critical overview.

PubMed

Deppermann, S; Storchak, H; Fallgatter, A J; Ehlis, A-C

2014-12-26

Stress is an adaptive response to demands of the environment and thus essential for survival. Exposure to stress triggers hypothalamic-pituitary-adrenocortical (HPA) axis activation and associated neurochemical reactions, following glucocorticoid release from the adrenal glands, accompanied by rapid physiological responses. Stimulation of this pathway results in the activation of specific brain regions, including the hippocampus, amygdala and prefrontal cortex which are enriched with glucocorticoid receptors (GRs). Recent findings indicate that the activation of GRs mediates the regulation of the brain-derived neurotrophic factor (BDNF). BDNF is crucial for neural plasticity, as it promotes cellular growth and synaptic changes. Hence stress-induced activation of these pathways leads to neuroplastic changes, including the formation of long-lasting memories of the experiences. As a consequence, organisms can learn from stressful events and respond in an adaptive manner to similar demands in the future. Whereas an optimal stress level leads to enhancement of memory performance, the exposure to extreme, traumatic or chronic stressors is a risk factor for psychopathologies which are associated with memory impairment and cognitive deficits such as posttraumatic stress disorder (PTSD). In this review article, we will outline the implications of stress exposure on memory formation involving the role of glucocorticoids and BDNF. Within this context, potential adverse effects of neuroplastic alterations will be discussed using the example of PTSD. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Microglia: An Interface between the Loss of Neuroplasticity and Depression

PubMed Central

Singhal, Gaurav; Baune, Bernhard T.

2017-01-01

Depression has been widely accepted as a major psychiatric disease affecting nearly 350 million people worldwide. Research focus is now shifting from studying the extrinsic and social factors of depression to the underlying molecular causes. Microglial activity is shown to be associated with pathological conditions, such as psychological stress, pathological aging, and chronic infections. These are primary immune effector cells in the CNS and regulate the extensive dialogue between the nervous and the immune systems in response to different immunological, physiological, and psychological stressors. Studies have suggested that during stress and pathologies, microglia play a significant role in the disruption of neuroplasticity and have detrimental effects on neuroprotection causing neuroinflammation and exacerbation of depression. After a systematic search of literature databases, relevant articles on the microglial regulation of bidirectional neuroimmune pathways affecting neuroplasticity and leading to depression were reviewed. Although, several hypotheses have been proposed for the microglial role in the onset of depression, it is clear that all molecular pathways to depression are linked through microglia-associated neuroinflammation and hippocampal degeneration. Molecular factors such as an excess of glucocorticoids and changes in gene expression of neurotrophic factors, as well as neuro active substances secreted by gut microbiota have also been shown to affect microglial morphology and phenotype resulting in depression. This review aims to critically analyze the various molecular pathways associated with the microglial role in depression. PMID:28943841

Electrifying the motor engram: effects of tDCS on motor learning and control.

PubMed

Orban de Xivry, Jean-Jacques; Shadmehr, Reza

2014-11-01

Learning to control our movements is accompanied by neuroplasticity of motor areas of the brain. The mechanisms of neuroplasticity are diverse and produce what is referred to as the motor engram, i.e., the neural trace of the motor memory. Transcranial direct current stimulation (tDCS) alters the neural and behavioral correlates of motor learning, but its precise influence on the motor engram is unknown. In this review, we summarize the effects of tDCS on neural activity and suggest a few key principles: (1) Firing rates are increased by anodal polarization and decreased by cathodal polarization, (2) anodal polarization strengthens newly formed associations, and (3) polarization modulates the memory of new/preferred firing patterns. With these principles in mind, we review the effects of tDCS on motor control, motor learning, and clinical applications. The increased spontaneous and evoked firing rates may account for the modulation of dexterity in non-learning tasks by tDCS. The facilitation of new association may account for the effect of tDCS on learning in sequence tasks while the ability of tDCS to strengthen memories of new firing patterns may underlie the effect of tDCS on consolidation of skills. We then describe the mechanisms of neuroplasticity of motor cortical areas and how they might be influenced by tDCS. We end with current challenges for the fields of brain stimulation and motor learning.

Neuroplasticity in Human Alcoholism

PubMed Central

Fein, George; Cardenas, Valerie A.

2015-01-01

Alcoholism is characterized by a lack of control over excessive alcohol consumption despite significant negative consequences. This impulsive and compulsive behavior may be related to functional abnormalities within networks of brain regions responsible for how we make decisions. The abnormalities may result in strengthened networks related to appetitive drive—or the need to fulfill desires—and simultaneously weakened networks that exercise control over behaviors. Studies using functional magnetic resonance imaging (fMRI) in abstinent alcoholics suggest that abstinence is associated with changes in the tone of such networks, decreasing resting tone in appetitive drive networks, and increasing resting tone in inhibitory control networks to support continued abstinence. Identifying electroencephalographic (EEG) measures of resting tone in these networks initially identified using fMRI, and establishing in longitudinal studies that these abstinence-related changes in network tone are progressive would motivate treatment initiatives to facilitate these changes in network tone, thereby supporting successful ongoing abstinence. PMID:26259093

Clozapine counteracts a ketamine-induced depression of hippocampal-prefrontal neuroplasticity and alters signaling pathway phosphorylation

PubMed Central

Rame, Marion; Caudal, Dorian; Schenker, Esther; Svenningsson, Per; Spedding, Michael; Jay, Thérèse M.

2017-01-01

Single sub-anesthetic doses of ketamine can exacerbate the symptoms of patients diagnosed with schizophrenia, yet similar ketamine treatments rapidly reduce depressive symptoms in major depression. Acute doses of the atypical antipsychotic drug clozapine have also been shown to counteract ketamine-induced psychotic effects. In the interest of understanding whether these drug effects could be modeled with alterations in neuroplasticity, we examined the impact of acutely-administered ketamine and clozapine on in vivo long-term potentiation (LTP) in the rat’s hippocampus-to-prefrontal cortex (H-PFC) pathway. We found that a low dose of ketamine depressed H-PFC LTP, whereas animals that were co-administrated the two drugs displayed LTP that was similar to a saline-treated control. To address which signaling molecules might mediate such effects, we also examined phosphorylation and total protein levels of GSK3β, GluA1, TrkB, ERK, and mTOR in prefrontal and hippocampal sub-regions. Among the statistically significant effects that were detected (a) both ketamine and clozapine increased the phosphorylation of Ser9-GSK3β throughout the prefrontal cortex and of Ser2481-mTOR in the dorsal hippocampus (DH), (b) clozapine increased the phosphorylation of Ser831-GluA1 throughout the prefrontal cortex and of Ser845-GluA1 in the ventral hippocampus, (c) ketamine treatment increased the phosphorylation of Thr202/Tyr204-ERK in the medial PFC (mPFC), and (d) clozapine treatment was associated with decreases in the phosphorylation of Tyr705-TrkB in the DH and of Try816-TrkB in the mPFC. Further analyses involving phosphorylation effect sizes also suggested Ser831-GluA1 in the PFC displayed the highest degree of clozapine-responsivity relative to ketamine. These results provide evidence for how ketamine and clozapine treatments affect neuroplasticity and signaling pathways in the stress-sensitive H-PFC network. They also demonstrate the potential relevance of H-PFC pathway neuroplasticity for modeling ketamine-clozapine interactions in regards to psychosis. PMID:28472198

Social Plasticity Relies on Different Neuroplasticity Mechanisms across the Brain Social Decision-Making Network in Zebrafish.

PubMed

Teles, Magda C; Cardoso, Sara D; Oliveira, Rui F

2016-01-01

Social living animals need to adjust the expression of their behavior to their status within the group and to changes in social context and this ability (social plasticity) has an impact on their Darwinian fitness. At the proximate level social plasticity must rely on neuroplasticity in the brain social decision-making network (SDMN) that underlies the expression of social behavior, such that the same neural circuit may underlie the expression of different behaviors depending on social context. Here we tested this hypothesis in zebrafish by characterizing the gene expression response in the SDMN to changes in social status of a set of genes involved in different types of neural plasticity: bdnf, involved in changes in synaptic strength; npas4, involved in contextual learning and dependent establishment of GABAergic synapses; neuroligins (nlgn1 and nlgn2) as synaptogenesis markers; and genes involved in adult neurogenesis (wnt3 and neurod). Four social phenotypes were experimentally induced: Winners and Losers of a real-opponent interaction; Mirror-fighters, that fight their own image in a mirror and thus do not experience a change in social status despite the expression of aggressive behavior; and non-interacting fish, which were used as a reference group. Our results show that each social phenotype (i.e., Winners, Losers, and Mirror-fighters) present specific patterns of gene expression across the SDMN, and that different neuroplasticity genes are differentially expressed in different nodes of the network (e.g., BDNF in the dorsolateral telencephalon, which is a putative teleost homolog of the mammalian hippocampus). Winners expressed unique patterns of gene co-expression across the SDMN, whereas in Losers and Mirror-fighters the co-expression patterns were similar in the dorsal regions of the telencephalon and in the supracommissural nucleus of the ventral telencephalic area, but differents in the remaining regions of the ventral telencephalon. These results indicate that social plasticity relies on multiple neuroplasticity mechanisms across the SDMN, and that there is not a single neuromolecular module underlying this type of behavioral flexibility.

Social Plasticity Relies on Different Neuroplasticity Mechanisms across the Brain Social Decision-Making Network in Zebrafish

PubMed Central

Teles, Magda C.; Cardoso, Sara D.; Oliveira, Rui F.

2016-01-01

Social living animals need to adjust the expression of their behavior to their status within the group and to changes in social context and this ability (social plasticity) has an impact on their Darwinian fitness. At the proximate level social plasticity must rely on neuroplasticity in the brain social decision-making network (SDMN) that underlies the expression of social behavior, such that the same neural circuit may underlie the expression of different behaviors depending on social context. Here we tested this hypothesis in zebrafish by characterizing the gene expression response in the SDMN to changes in social status of a set of genes involved in different types of neural plasticity: bdnf, involved in changes in synaptic strength; npas4, involved in contextual learning and dependent establishment of GABAergic synapses; neuroligins (nlgn1 and nlgn2) as synaptogenesis markers; and genes involved in adult neurogenesis (wnt3 and neurod). Four social phenotypes were experimentally induced: Winners and Losers of a real-opponent interaction; Mirror-fighters, that fight their own image in a mirror and thus do not experience a change in social status despite the expression of aggressive behavior; and non-interacting fish, which were used as a reference group. Our results show that each social phenotype (i.e., Winners, Losers, and Mirror-fighters) present specific patterns of gene expression across the SDMN, and that different neuroplasticity genes are differentially expressed in different nodes of the network (e.g., BDNF in the dorsolateral telencephalon, which is a putative teleost homolog of the mammalian hippocampus). Winners expressed unique patterns of gene co-expression across the SDMN, whereas in Losers and Mirror-fighters the co-expression patterns were similar in the dorsal regions of the telencephalon and in the supracommissural nucleus of the ventral telencephalic area, but differents in the remaining regions of the ventral telencephalon. These results indicate that social plasticity relies on multiple neuroplasticity mechanisms across the SDMN, and that there is not a single neuromolecular module underlying this type of behavioral flexibility. PMID:26909029

Effects of vitamin D supplementation on neuroplasticity in older adults: a double-blinded, placebo-controlled randomised trial.

PubMed

Pirotta, S; Kidgell, D J; Daly, R M

2015-01-01

Vitamin D can improve muscle function and reduce falls, but whether it can strengthen neural connections within the brain and nervous system is not known. This 10-week randomised controlled trial indicates that treatment with 2,000 IU/day vitamin D3 does not significantly alter neuroplasticity relative to placebo in older adults. The purpose of this study was to examine the effects of vitamin D supplementation on neuroplasticity, serum brain-derived neurotrophic factor (BDNF) and muscle strength and function in older adults. This was a 10-week double-blinded, placebo-controlled randomised trial in which 26 older adults with 25-hydroxyvitamin D [25OHD] concentrations 25-60 nmol/L were randomised to 2,000 IU/day vitamin D3 or matched placebo. Single- and paired-pulse transcranial magnetic stimulation applied over the motor cortex was used to assess changes in motor-evoked potentials (MEPs) and short-interval intracortical inhibition (SICI), as measures of corticospinal excitability and inhibition respectively, by recording electromyography (EMG) responses to stimulation from the wrist extensors. Changes in muscle strength, stair climbing power, gait (timed-up-and-go), dynamic balance (four square step test), serum 25(OH)D and BDNF concentrations were also measured. After 10 weeks, mean 25(OH)D levels increased from 46 to 81 nmol/L in the vitamin D group with no change in the placebo group. The vitamin D group experienced a significant 8-11% increase in muscle strength and a reduction in cortical excitability (MEP amplitude) and SICI relative to baseline (all P < 0.05), but these changes were not significantly different from placebo. There was no effect of vitamin D on muscle power, function or BDNF. Daily supplementation with 2,000 IU vitamin D3 for 10 weeks had no significant effect on neuroplasticity compared to placebo, but the finding that vitamin D treatment alone was associated with a decrease in corticospinal excitability and intracortical inhibition warrants further investigation as this suggests that it may improve the efficacy of neural transmission within the corticospinal pathway.

Neurocognitive and Neuroplastic Mechanisms of Novel Clinical Signs in CRPS.

PubMed

Kuttikat, Anoop; Noreika, Valdas; Shenker, Nicholas; Chennu, Srivas; Bekinschtein, Tristan; Brown, Christopher Andrew

2016-01-01

Complex regional pain syndrome (CRPS) is a chronic, debilitating pain condition that usually arises after trauma to a limb, but its precise etiology remains elusive. Novel clinical signs based on body perceptual disturbances have been reported, but their pathophysiological mechanisms remain poorly understood. Investigators have used functional neuroimaging techniques (including MEG, EEG, fMRI, and PET) to study changes mainly within the somatosensory and motor cortices. Here, we provide a focused review of the neuroimaging research findings that have generated insights into the potential neurocognitive and neuroplastic mechanisms underlying perceptual disturbances in CRPS. Neuroimaging findings, particularly with regard to somatosensory processing, have been promising but limited by a number of technique-specific factors (such as the complexity of neuroimaging investigations, poor spatial resolution of EEG/MEG, and use of modeling procedures that do not draw causal inferences) and more general factors including small samples sizes and poorly characterized patients. These factors have led to an underappreciation of the potential heterogeneity of pathophysiology that may underlie variable clinical presentation in CRPS. Also, until now, neurological deficits have been predominantly investigated separately from perceptual and cognitive disturbances. Here, we highlight the need to identify neurocognitive phenotypes of patients with CRPS that are underpinned by causal explanations for perceptual disturbances. We suggest that a combination of larger cohorts, patient phenotyping, the use of both high temporal, and spatial resolution neuroimaging methods, and the identification of simplified biomarkers is likely to be the most fruitful approach to identifying neurocognitive phenotypes in CRPS. Based on our review, we explain how such phenotypes could be characterized in terms of hierarchical models of perception and corresponding disturbances in recurrent processing involving the somatosensory, salience and executive brain networks. We also draw attention to complementary neurological factors that may explain some CRPS symptoms, including the possibility of central neuroinflammation and neuronal atrophy, and how these phenomena may overlap but be partially separable from neurocognitive deficits.

Neurocognitive and Neuroplastic Mechanisms of Novel Clinical Signs in CRPS

PubMed Central

Kuttikat, Anoop; Noreika, Valdas; Shenker, Nicholas; Chennu, Srivas; Bekinschtein, Tristan; Brown, Christopher Andrew

2016-01-01

Complex regional pain syndrome (CRPS) is a chronic, debilitating pain condition that usually arises after trauma to a limb, but its precise etiology remains elusive. Novel clinical signs based on body perceptual disturbances have been reported, but their pathophysiological mechanisms remain poorly understood. Investigators have used functional neuroimaging techniques (including MEG, EEG, fMRI, and PET) to study changes mainly within the somatosensory and motor cortices. Here, we provide a focused review of the neuroimaging research findings that have generated insights into the potential neurocognitive and neuroplastic mechanisms underlying perceptual disturbances in CRPS. Neuroimaging findings, particularly with regard to somatosensory processing, have been promising but limited by a number of technique-specific factors (such as the complexity of neuroimaging investigations, poor spatial resolution of EEG/MEG, and use of modeling procedures that do not draw causal inferences) and more general factors including small samples sizes and poorly characterized patients. These factors have led to an underappreciation of the potential heterogeneity of pathophysiology that may underlie variable clinical presentation in CRPS. Also, until now, neurological deficits have been predominantly investigated separately from perceptual and cognitive disturbances. Here, we highlight the need to identify neurocognitive phenotypes of patients with CRPS that are underpinned by causal explanations for perceptual disturbances. We suggest that a combination of larger cohorts, patient phenotyping, the use of both high temporal, and spatial resolution neuroimaging methods, and the identification of simplified biomarkers is likely to be the most fruitful approach to identifying neurocognitive phenotypes in CRPS. Based on our review, we explain how such phenotypes could be characterized in terms of hierarchical models of perception and corresponding disturbances in recurrent processing involving the somatosensory, salience and executive brain networks. We also draw attention to complementary neurological factors that may explain some CRPS symptoms, including the possibility of central neuroinflammation and neuronal atrophy, and how these phenomena may overlap but be partially separable from neurocognitive deficits. PMID:26858626

Regional Neuroplastic Brain Changes in Patients with Chronic Inflammatory and Non-Inflammatory Visceral Pain

PubMed Central

Hong, Jui-Yang; Labus, Jennifer S.; Jiang, Zhiguo; Ashe-Mcnalley, Cody; Dinov, Ivo; Gupta, Arpana; Shi, Yonggang; Stains, Jean; Heendeniya, Nuwanthi; Smith, Suzanne R.; Tillisch, Kirsten; Mayer, Emeran A.

2014-01-01

Regional cortical thickness alterations have been reported in many chronic inflammatory and painful conditions, including inflammatory bowel diseases (IBD) and irritable bowel syndrome (IBS), even though the mechanisms underlying such neuroplastic changes remain poorly understood. In order to better understand the mechanisms contributing to grey matter changes, the current study sought to identify the differences in regional alterations in cortical thickness between healthy controls and two chronic visceral pain syndromes, with and without chronic gut inflammation. 41 healthy controls, 11 IBS subjects with diarrhea, and 16 subjects with ulcerative colitis (UC) underwent high-resolution T1-weighted magnetization-prepared rapid acquisition gradient echo scans. Structural image preprocessing and cortical thickness analysis within the region of interests were performed by using the Laboratory of Neuroimaging Pipeline. Group differences were determined using the general linear model and linear contrast analysis. The two disease groups differed significantly in several cortical regions. UC subjects showed greater cortical thickness in anterior cingulate cortical subregions, and in primary somatosensory cortex compared with both IBS and healthy subjects. Compared with healthy subjects, UC subjects showed lower cortical thickness in orbitofrontal cortex and in mid and posterior insula, while IBS subjects showed lower cortical thickness in the anterior insula. Large effects of correlations between symptom duration and thickness in the orbitofrontal cortex and postcentral gyrus were only observed in UC subjects. The findings suggest that the mechanisms underlying the observed gray matter changes in UC subjects represent a consequence of peripheral inflammation, while in IBS subjects central mechanisms may play a primary role. PMID:24416245

D-cycloserine in Schizophrenia: New Strategies for Improving Clinical Outcomes by Enhancing Plasticity

PubMed Central

Goff, Donald C.

2017-01-01

Background Dysregulation of N-methyl D-aspartate (NMDA) receptor signaling is strongly implicated in schizophrenia. Based on the ketamine model of NMDA receptor hypoactivity, therapeutic approaches designed to maintain a sustained increase in agonist activity at the glycine site of the NMDA receptor have produced promising, although inconsistent, efficacy for negative symptoms. Methods A review of the published literature on D-cycloserine (DCS) pharmacology in animal models and in clinical studies was performed. Findings relevant to DCS effects on memory and plasticity and their potential clinical application to schizophrenia were summarized. Results Studies in animals and clinical trials in patients with anxiety disorders have demonstrated that single or intermittent dosing with DCS enhances memory consolidation. Preliminary trials in patients with schizophrenia suggest that intermittent dosing with DCS may produce persistent improvement of negative symptoms and enhance learning when combined with cognitive behavioral therapy for delusions or with cognitive remediation. The pharmacology of DCS is complex, since it acts as a “super agonist” at NMDA receptors containing GluN2C subunits and, under certain conditions, it may act as an antagonist at NMDA receptors containing GluN2B subunits. Conclusions There are preliminary findings that support a role for D-cycloserine in schizophrenia as a strategy to enhance neuroplasticity and memory. However, additional studies with DCS are needed to confirm these findings. In addition, clinical trials with positive and negative allosteric modulators with greater specificity for NMDA receptor subtypes are needed to identify the optimal strategy for enhancing neuroplasticity in schizophrenia. PMID:26915421

Phantom limbs: pain, embodiment, and scientific advances in integrative therapies.

PubMed

Lenggenhager, Bigna; Arnold, Carolyn A; Giummarra, Melita J

2014-03-01

Research over the past two decades has begun to identify some of the key mechanisms underlying phantom limb pain and sensations; however, this continues to be a clinically challenging condition to manage. Treatment of phantom pain, like all chronic pain conditions, demands a holistic approach that takes into consideration peripheral, spinal, and central neuroplastic mechanisms. In this review, we focus on nonpharmacological treatments tailored to reverse the maladaptive neuroplasticity associated with phantom pain. Recent scientific advances emerging from interdisciplinary research between neuroscience, virtual reality, robotics, and prosthetics show the greatest promise for alternative embodiment and maintaining the integrity of the multifaceted representation of the body in the brain. Importantly, these advances have been found to prevent and reduce phantom limb pain. In particular, therapies that involve sensory and/or motor retraining, most naturally through the use of integrative prosthetic devices, as well as peripheral (e.g., transcutaneous electrical nerve stimulation) or central (e.g., transcranial magnetic stimulation or deep brain stimulation) stimulation techniques, have been found to both restore the neural representation of the missing limb and to reduce the intensity of phantom pain. While the evidence for the efficacy of these therapies is mounting, but well-controlled and large-scale studies are still needed. WIREs Cogn Sci 2014, 5:221-231. doi: 10.1002/wcs.1277 CONFLICT OF INTEREST: The authors have no financial or other relationship that might lead to a conflict of interest. For further resources related to this article, please visit the WIREs website. © 2014 John Wiley & Sons, Ltd.

Neural substrates of treatment response to cognitive-behavioral therapy in panic disorder with agoraphobia.

PubMed

Lueken, Ulrike; Straube, Benjamin; Konrad, Carsten; Wittchen, Hans-Ulrich; Ströhle, Andreas; Wittmann, André; Pfleiderer, Bettina; Uhlmann, Christina; Arolt, Volker; Jansen, Andreas; Kircher, Tilo

2013-11-01

Although exposure-based cognitive-behavioral therapy (CBT) is an effective treatment option for panic disorder with agoraphobia, the neural substrates of treatment response remain unknown. Evidence suggests that panic disorder with agoraphobia is characterized by dysfunctional safety signal processing. Using fear conditioning as a neurofunctional probe, the authors investigated neural baseline characteristics and neuroplastic changes after CBT that were associated with treatment outcome in patients with panic disorder with agoraphobia. Neural correlates of fear conditioning and extinction were measured using functional MRI before and after a manualized CBT program focusing on behavioral exposure in 49 medication-free patients with a primary diagnosis of panic disorder with agoraphobia. Treatment response was defined as a reduction exceeding 50% in Hamilton Anxiety Rating Scale scores. At baseline, nonresponders exhibited enhanced activation in the right pregenual anterior cingulate cortex, the hippocampus, and the amygdala in response to a safety signal. While this activation pattern partly resolved in nonresponders after CBT, successful treatment was characterized by increased right hippocampal activation when processing stimulus contingencies. Treatment response was associated with an inhibitory functional coupling between the anterior cingulate cortex and the amygdala that did not change over time. This study identified brain activation patterns associated with treatment response in patients with panic disorder with agoraphobia. Altered safety signal processing and anterior cingulate cortex-amygdala coupling may indicate individual differences among these patients that determine the effectiveness of exposure-based CBT and associated neuroplastic changes. Findings point to brain networks by which successful CBT in this patient population is mediated.

Recruitment of Staufen2 Enhances Dendritic Localization of an Intron-Containing CaMKIIα mRNA.

PubMed

Ortiz, Raúl; Georgieva, Maya V; Gutiérrez, Sara; Pedraza, Neus; Fernández-Moya, Sandra M; Gallego, Carme

2017-07-05

Regulation of mRNA localization is a conserved cellular process observed in many types of cells and organisms. Asymmetrical mRNA distribution plays a particularly important role in the nervous system, where local translation of localized mRNA represents a key mechanism in synaptic plasticity. CaMKIIα is a very abundant mRNA detected in neurites, consistent with its crucial role at glutamatergic synapses. Here, we report the presence of CaMKIIα mRNA isoforms that contain intron i16 in dendrites, RNA granules, and synaptoneurosomes from primary neurons and brain. This subpopulation of unspliced mRNA preferentially localizes to distal dendrites in a synaptic-activity-dependent manner. Staufen2, a well-established marker of RNA transport in dendrites, interacts with intron i16 sequences and enhances its distal dendritic localization, pointing to the existence of intron-mediated mechanisms in the molecular pathways that modulate dendritic transport and localization of synaptic mRNAs. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Pornography addiction - a supranormal stimulus considered in the context of neuroplasticity.

PubMed

Hilton, Donald L

2013-01-01

Addiction has been a divisive term when applied to various compulsive sexual behaviors (CSBs), including obsessive use of pornography. Despite a growing acceptance of the existence of natural or process addictions based on an increased understanding of the function of the mesolimbic dopaminergic reward systems, there has been a reticence to label CSBs as potentially addictive. While pathological gambling (PG) and obesity have received greater attention in functional and behavioral studies, evidence increasingly supports the description of CSBs as an addiction. This evidence is multifaceted and is based on an evolving understanding of the role of the neuronal receptor in addiction-related neuroplasticity, supported by the historical behavioral perspective. This addictive effect may be amplified by the accelerated novelty and the 'supranormal stimulus' (a phrase coined by Nikolaas Tinbergen) factor afforded by Internet pornography.

Transcranial magnetic stimulation and neuroplasticity.

PubMed

Pascual-Leone, A; Tarazona, F; Keenan, J; Tormos, J M; Hamilton, R; Catala, M D

1999-02-01

We review past results and present novel data to illustrate different ways in which TMS can be used to study neural plasticity. Procedural learning during the serial reaction time task (SRTT) is used as a model of neural plasticity to illustrate the applications of TMS. These different applications of TMS represent principles of use that we believe are applicable to studies of cognitive neuroscience in general and exemplify the great potential of TMS in the study of brain and behavior. We review the use of TMS for (1) cortical output mapping using focal, single-pulse TMS; (2) identification of the mechanisms underlying neuroplasticity using paired-pulse TMS techniques; (3) enhancement of the information of other neuroimaging techniques by transient disruption of cortical function using repetitive TMS; and finally (4) modulation of cortical function with repetitive TMS to influence behavior and guide plasticity.

Neuroplasticity and Clinical Practice: Building Brain Power for Health.

PubMed

Shaffer, Joyce

2016-01-01

The focus of this review is on driving neuroplasticity in a positive direction using evidence-based interventions that also have the potential to improve general health. One goal is to provide an overview of the many ways new neuroscience can inform treatment protocols to empower and motivate clients to make the lifestyle choices that could help build brain power and could increase adherence to healthy lifestyle changes that have also been associated with simultaneously enhancing vigorous longevity, health, happiness, and wellness. Another goal is to explore the use of a focus in clinical practice on helping clients appreciate this new evidence and use evolving neuroscience in establishing individualized goals, designing strategies for achieving them and increasing treatment compliance. The timing is urgent for such interventions with goals of enhancing brain health across the lifespan and improving statistics on dementia worldwide.

Neuroplasticity and Clinical Practice: Building Brain Power for Health

PubMed Central

Shaffer, Joyce

2016-01-01

The focus of this review is on driving neuroplasticity in a positive direction using evidence-based interventions that also have the potential to improve general health. One goal is to provide an overview of the many ways new neuroscience can inform treatment protocols to empower and motivate clients to make the lifestyle choices that could help build brain power and could increase adherence to healthy lifestyle changes that have also been associated with simultaneously enhancing vigorous longevity, health, happiness, and wellness. Another goal is to explore the use of a focus in clinical practice on helping clients appreciate this new evidence and use evolving neuroscience in establishing individualized goals, designing strategies for achieving them and increasing treatment compliance. The timing is urgent for such interventions with goals of enhancing brain health across the lifespan and improving statistics on dementia worldwide. PMID:27507957

Pornography addiction – a supranormal stimulus considered in the context of neuroplasticity

PubMed Central

Hilton, Donald L.

2013-01-01

Addiction has been a divisive term when applied to various compulsive sexual behaviors (CSBs), including obsessive use of pornography. Despite a growing acceptance of the existence of natural or process addictions based on an increased understanding of the function of the mesolimbic dopaminergic reward systems, there has been a reticence to label CSBs as potentially addictive. While pathological gambling (PG) and obesity have received greater attention in functional and behavioral studies, evidence increasingly supports the description of CSBs as an addiction. This evidence is multifaceted and is based on an evolving understanding of the role of the neuronal receptor in addiction-related neuroplasticity, supported by the historical behavioral perspective. This addictive effect may be amplified by the accelerated novelty and the ‘supranormal stimulus’ (a phrase coined by Nikolaas Tinbergen) factor afforded by Internet pornography. PMID:24693354

[Patterns of brain ageing].

PubMed

Fernández Viadero, Carlos; Verduga Vélez, Rosario; Crespo Santiago, Dámaso

2017-06-01

Neuroplasticity lends the brain a strong ability to adapt to changes in the environment that occur during ageing. Animal models have shown alterations in neurotransmission and imbalances in the expression of neural growth factor. Changes at the morphometric level are not constant. Volume loss is related to alterations in neuroplasticity and involvement of the cerebral neuropil. Although there are no conclusive data, physical exercise improves the molecular, biological, functional and behavioural-cognitive changes associated with brain ageing. The aged human brain has been described as showing weight and volume loss and increased ventricular size. However, neuroimaging shows significant variation and many healthy elderly individuals show no significant macroscopic changes. In most brain regions, the number of neurons remains stable throughout life. Neuroplasticity does not disappear with ageing, and changes in dendritic arborization and the density of spines and synapses are more closely related to brain activity than to age. At the molecular level, although the presence of altered Tau and β-amyloid proteins is used as a biomarker of neurodegenerative disease, postmortem studies show that these abnormal proteins are common in the brains of elderly people without dementia. Finally, due to the relationship between neurodegenerative diseases and metabolic alterations, this article analyses the influence of insulin-like growth factor and ageing, both in animal models and in humans, and the possible neuroprotective effect of insulin. Copyright © 2017 Sociedad Española de Geriatría y Gerontología. Publicado por Elsevier España, S.L.U. All rights reserved.

Fluoxetine Increases Hippocampal Neurogenesis and Induces Epigenetic Factors But Does Not Improve Functional Recovery after Traumatic Brain Injury

PubMed Central

Wang, Yonggang; Neumann, Melanie; Hansen, Katharina; Hong, Shuwhey M.; Kim, Sharon; Noble-Haeusslein, Linda J.

2011-01-01

Abstract The selective serotonin reuptake inhibitor fluoxetine induces hippocampal neurogenesis, stimulates maturation and synaptic plasticity of adult hippocampal neurons, and reduces motor/sensory and memory impairments in several CNS disorders. In the setting of traumatic brain injury (TBI), its effects on neuroplasticity and function have yet to be thoroughly investigated. Here we examined the efficacy of fluoxetine after a moderate to severe TBI, produced by a controlled cortical impact. Three days after TBI or sham surgery, mice were treated with fluoxetine (10 mg/kg/d) or vehicle for 4 weeks. To evaluate the effects of fluoxetine on neuroplasticity, hippocampal neurogenesis and epigenetic modification were studied. Stereologic analysis of the dentate gyrus revealed a significant increase in doublecortin-positive cells in brain-injured animals treated with fluoxetine relative to controls, a finding consistent with enhanced hippocampal neurogenesis. Epigenetic modifications, including an increase in histone 3 acetylation and induction of methyl-CpG-binding protein, a transcription factor involved in DNA methylation, were likewise seen by immunohistochemistry and quantitative Western immunoblots, respectively, in brain-injured animals treated with fluoxetine. To determine if fluoxetine improves neurological outcomes after TBI, gait function and spatial learning and memory were assessed by the CatWalk-assisted gait test and Barnes maze test, respectively. No differences in these parameters were seen between fluoxetine- and vehicle-treated animals. Thus while fluoxetine enhanced neuroplasticity in the hippocampus after TBI, its chronic administration did not restore locomotor function or ameliorate memory deficits. PMID:21175261

Plasticity in the sensorimotor cortex induced by Music-supported therapy in stroke patients: a TMS study.

PubMed

Grau-Sánchez, Jennifer; Amengual, Julià L; Rojo, Nuria; Veciana de Las Heras, Misericordia; Montero, Jordi; Rubio, Francisco; Altenmüller, Eckart; Münte, Thomas F; Rodríguez-Fornells, Antoni

2013-01-01

Playing a musical instrument demands the engagement of different neural systems. Recent studies about the musician's brain and musical training highlight that this activity requires the close interaction between motor and somatosensory systems. Moreover, neuroplastic changes have been reported in motor-related areas after short and long-term musical training. Because of its capacity to promote neuroplastic changes, music has been used in the context of stroke neurorehabilitation. The majority of patients suffering from a stroke have motor impairments, preventing them to live independently. Thus, there is an increasing demand for effective restorative interventions for neurological deficits. Music-supported Therapy (MST) has been recently developed to restore motor deficits. We report data of a selected sample of stroke patients who have been enrolled in a MST program (1 month intense music learning). Prior to and after the therapy, patients were evaluated with different behavioral motor tests. Transcranial Magnetic Stimulation (TMS) was applied to evaluate changes in the sensorimotor representations underlying the motor gains observed. Several parameters of excitability of the motor cortex were assessed as well as the cortical somatotopic representation of a muscle in the affected hand. Our results revealed that participants obtained significant motor improvements in the paretic hand and those changes were accompanied by changes in the excitability of the motor cortex. Thus, MST leads to neuroplastic changes in the motor cortex of stroke patients which may explain its efficacy.

Hemispheric contributions to language reorganisation: An MEG study of neuroplasticity in chronic post stroke aphasia.

PubMed

Mohr, Bettina; MacGregor, Lucy J; Difrancesco, Stephanie; Harrington, Karen; Pulvermüller, Friedemann; Shtyrov, Yury

2016-12-01

Previous studies have demonstrated that efficient neurorehabilitation in post stroke aphasia leads to clinical language improvements and promotes neuroplasticity. Brain areas frequently implicated in functional restitution of language after stroke comprise perilesional sites in the left hemisphere and homotopic regions in the right hemisphere. However, the neuronal mechanisms underlying therapy-induced language restitution are still largely unclear. In this study, magnetoencephalography was used to investigate neurophysiological changes in a group of chronic aphasia patients who underwent intensive language action therapy (ILAT), also known as constraint-induced aphasia therapy (CIAT). Before and immediately after ILAT, patients' language and communication skills were assessed and their brain responses were recorded during a lexical magnetic mismatch negativity (MMNm) paradigm, presenting familiar spoken words and meaningless pseudowords. After the two-week therapy interval, patients showed significant clinical improvements of language and communication skills. Spatio-temporal dynamics of neuronal changes revealed a significant increase in word-specific neuro-magnetic MMNm activation around 200ms after stimulus identification points. This enhanced brain response occurred specifically for words and was most pronounced over perilesional areas in the left hemisphere. Therapy-related changes in neuromagnetic activation for words in both hemispheres significantly correlated with performance on a clinical language test. The findings indicate that functional recovery of language in chronic post stroke aphasia is associated with neuroplastic changes in both cerebral hemispheres, with stronger left-hemispheric contribution during automatic stages of language processing. Copyright © 2016 Elsevier Ltd. All rights reserved.

Plasticity in the sensorimotor cortex induced by Music-supported therapy in stroke patients: a TMS study

PubMed Central

Grau-Sánchez, Jennifer; Amengual, Julià L.; Rojo, Nuria; Veciana de las Heras, Misericordia; Montero, Jordi; Rubio, Francisco; Altenmüller, Eckart; Münte, Thomas F.; Rodríguez-Fornells, Antoni

2013-01-01

Playing a musical instrument demands the engagement of different neural systems. Recent studies about the musician's brain and musical training highlight that this activity requires the close interaction between motor and somatosensory systems. Moreover, neuroplastic changes have been reported in motor-related areas after short and long-term musical training. Because of its capacity to promote neuroplastic changes, music has been used in the context of stroke neurorehabilitation. The majority of patients suffering from a stroke have motor impairments, preventing them to live independently. Thus, there is an increasing demand for effective restorative interventions for neurological deficits. Music-supported Therapy (MST) has been recently developed to restore motor deficits. We report data of a selected sample of stroke patients who have been enrolled in a MST program (1 month intense music learning). Prior to and after the therapy, patients were evaluated with different behavioral motor tests. Transcranial Magnetic Stimulation (TMS) was applied to evaluate changes in the sensorimotor representations underlying the motor gains observed. Several parameters of excitability of the motor cortex were assessed as well as the cortical somatotopic representation of a muscle in the affected hand. Our results revealed that participants obtained significant motor improvements in the paretic hand and those changes were accompanied by changes in the excitability of the motor cortex. Thus, MST leads to neuroplastic changes in the motor cortex of stroke patients which may explain its efficacy. PMID:24027507

Bite or brain: Implication of sensorimotor regulation and neuroplasticity in oral rehabilitation procedures.

PubMed

Kumar, A; Kothari, M; Grigoriadis, A; Trulsson, M; Svensson, P

2018-04-01

Tooth loss, decreased mass and strength of the masticatory muscles leading to difficulty in chewing have been suggested as important determinants of eating and nutrition in the elderly. To compensate for the loss of teeth, in particular, a majority of the elderly rely on dental prosthesis for chewing. Chewing function is indeed an important aspect of oral health, and therefore, oral rehabilitation procedures should aim to restore or maintain adequate function. However, even if the possibilities to anatomically restore lost teeth and occlusion have never been better; conventional rehabilitation procedures may still fail to optimally restore oral functions. Perhaps this is due to the lack of focus on the importance of the brain in the rehabilitation procedures. Therefore, the aim of this narrative review was to discuss the importance of maintaining or restoring optimum chewing function in the superageing population and to summarise the emerging studies on oral motor task performance and measures of cortical neuroplasticity induced by systematic training paradigms in healthy participants. Further, brain imaging studies in patients undergoing or undergone oral rehabilitation procedures will be discussed. Overall, this information is believed to enhance the understanding and develop better rehabilitative strategies to exploit training-induced cortical neuroplasticity in individuals affected by impaired oral motor coordination and function. Training or relearning of oral motor tasks could be important to optimise masticatory performance in dental prosthesis users and may represent a much-needed paradigm shift in the approach to oral rehabilitation procedures. © 2018 John Wiley & Sons Ltd.

Brain and Cognitive Reserve: Translation via Network Control Theory

PubMed Central

Medaglia, John Dominic; Pasqualetti, Fabio; Hamilton, Roy H.; Thompson-Schill, Sharon L.; Bassett, Danielle S.

2017-01-01

Traditional approaches to understanding the brain’s resilience to neuropathology have identified neurophysiological variables, often described as brain or cognitive “reserve,” associated with better outcomes. However, mechanisms of function and resilience in large-scale brain networks remain poorly understood. Dynamic network theory may provide a basis for substantive advances in understanding functional resilience in the human brain. In this perspective, we describe recent theoretical approaches from network control theory as a framework for investigating network level mechanisms underlying cognitive function and the dynamics of neuroplasticity in the human brain. We describe the theoretical opportunities offered by the application of network control theory at the level of the human connectome to understand cognitive resilience and inform translational intervention. PMID:28104411

Neuroplasticity of the Sensorimotor Cortex during Learning

PubMed Central

Francis, Joseph Thachil; Song, Weiguo

2011-01-01

We will discuss some of the current issues in understanding plasticity in the sensorimotor (SM) cortices on the behavioral, neurophysiological, and synaptic levels. We will focus our paper on reaching and grasping movements in the rat. In addition, we will discuss our preliminary work utilizing inhibition of protein kinase Mζ (PKMζ), which has recently been shown necessary and sufficient for the maintenance of long-term potentiation (LTP) (Ling et al., 2002). With this new knowledge and inhibitors to this system, as well as the ability to overexpress this system, we can start to directly modulate LTP and determine its influence on behavior as well as network level processing dependent at least in part due to this form of LTP. We will also briefly introduce the use of brain machine interface (BMI) paradigms to ask questions about sensorimotor plasticity and discuss current analysis techniques that may help in our understanding of neuroplasticity. PMID:21949908

Playing a first-person shooter video game induces neuroplastic change.

PubMed

Wu, Sijing; Cheng, Cho Kin; Feng, Jing; D'Angelo, Lisa; Alain, Claude; Spence, Ian

2012-06-01

Playing a first-person shooter (FPS) video game alters the neural processes that support spatial selective attention. Our experiment establishes a causal relationship between playing an FPS game and neuroplastic change. Twenty-five participants completed an attentional visual field task while we measured ERPs before and after playing an FPS video game for a cumulative total of 10 hr. Early visual ERPs sensitive to bottom-up attentional processes were little affected by video game playing for only 10 hr. However, participants who played the FPS video game and also showed the greatest improvement on the attentional visual field task displayed increased amplitudes in the later visual ERPs. These potentials are thought to index top-down enhancement of spatial selective attention via increased inhibition of distractors. Individual variations in learning were observed, and these differences show that not all video game players benefit equally, either behaviorally or in terms of neural change.

The neuroplastic effect of working memory training in healthy volunteers and patients with schizophrenia: Implications for cognitive rehabilitation.

PubMed

Li, Xu; Xiao, Ya-hui; Zhao, Qing; Leung, Ada W W; Cheung, Eric F C; Chan, Raymond C K

2015-08-01

We conducted an activation likelihood estimation (ALE) meta-analysis to quantitatively review the existing working memory (WM) training studies that investigated neural activation changes both in healthy individuals and patients with schizophrenia. ALE analysis of studies in healthy individuals indicates a widespread distribution of activation changes with WM training in the frontal and parietal regions, especially the dorsolateral prefrontal cortex, the medial frontal cortex and the precuneus, as well as subcortical regions such as the insula and the striatum. WM training is also accompanied by activation changes in patients with schizophrenia, mainly in the dorsolateral prefrontal cortex, the precuneus and the fusiform gyrus. Our results demonstrate that WM training is accompanied by changes in neural activation patterns in healthy individuals, which may provide the basis for understanding neuroplastic changes in patients with schizophrenia. Copyright © 2015 Elsevier Ltd. All rights reserved.

Neuroplastic effects of music lessons on hippocampal volume in children with congenital hypothyroidism.

PubMed

Zendel, Benjamin Rich; Willoughby, Karen A; Rovet, Joanne F

2013-12-04

Children with congenital hypothyroidism (CH) who experience a neonatal thyroid hormone deficiency have reduced hippocampal volumes compared with healthy controls. Interestingly, evidence suggests that musical training can contribute to structural plasticity in a number of brain areas, including the hippocampus. Therefore, we investigated whether taking music lessons could ameliorate the volumetric reductions of the hippocampus in children with CH. Left and right hippocampal volumes were measured in four groups of children: children with CH with and without music lessons, and healthy controls with and without music lessons. We found that the volume of the right hippocampus was comparable between children with CH who had taken music lessons and the healthy controls. Children with CH who had not taken music lessons had reduced hippocampal volumes compared with the other three groups. These results suggest that music lessons may induce structural neuroplasticity in children with atypical hippocampal development because of early thyroid hormone deficiencies.

Intermittent metabolic switching, neuroplasticity and brain health

PubMed Central

Mattson, Mark P.; Moehl, Keelin; Ghena, Nathaniel; Schmaedick, Maggie; Cheng, Aiwu

2018-01-01

During evolution, individuals whose brains and bodies functioned well in a fasted state were successful in acquiring food, enabling their survival and reproduction. With fasting and extended exercise, liver glycogen stores are depleted and ketones are produced from adipose-cell-derived fatty acids. This metabolic switch in cellular fuel source is accompanied by cellular and molecular adaptations of neural networks in the brain that enhance their functionality and bolster their resistance to stress, injury and disease. Here, we consider how intermittent metabolic switching, repeating cycles of a metabolic challenge that induces ketosis (fasting and/or exercise) followed by a recovery period (eating, resting and sleeping), may optimize brain function and resilience throughout the lifespan, with a focus on the neuronal circuits involved in cognition and mood. Such metabolic switching impacts multiple signalling pathways that promote neuroplasticity and resistance of the brain to injury and disease. PMID:29321682

Mass-related traumatic tissue displacement and behavior: a screen for treatments that reduce [corrected] harm to bystander cells and recovery of function.

PubMed

Yang, Hongyan; Preston, Marnie; Chopp, Michael; Jiang, Feng; Zhang, Xuepeng; Schallert, Timothy

2006-05-01

In this study, we focused on a preclinical model of brain compression injury that has relevance to pathological conditions such as tumor, hematoma, blood clot, and intracerebral bony fragment. We investigated behavioral impairment as a result of rapid-onset small mass, and the factors involved in lesion formation and neuroplasticity. An epidural bead implantation method was adopted. Two sizes (1.5 mm and 2.0 mm thick) of hemisphere-shaped beads were used. The beads were implanted into various locations over the sensorimotor cortex (SMC--anterior, middle and posterior). The effects of early versus delayed bead removal were examined to model clinical neurosurgical or other treatment procedures. Forelimb and hind-limb behavioral deficits and recovery were observed, and histological changes were quantified to determine brain reaction to focal compression. Our results showed that the behavioral deficits of compression were influenced by the location, timing of compression release, and magnitude of compression. Even persistent compression by the thicker bead (2.0 mm) caused only minor behavioral deficits, followed by fast recovery within a week in most animals, suggesting a mild lesion pattern for this model. Brain tissue was compressed into a deformed shape under pressure with slight tissue damage, evidenced by pathological evaluation on hematoxylin and eosin (H&E)- and TUNEL-stained sections. Detectable but not severe behavioral dysfunction exhibited by this model makes it particularly suitable for direct assessment of adverse effects of interventions on neuroplasticity after brain compression injury. This model may permit development of treatment strategies to alleviate brain mass effects, without disrupting neuroplasticity.

A Single Bout of High-Intensity Interval Training Improves Motor Skill Retention in Individuals With Stroke.

PubMed

Nepveu, Jean-Francois; Thiel, Alexander; Tang, Ada; Fung, Joyce; Lundbye-Jensen, Jesper; Boyd, Lara A; Roig, Marc

2017-08-01

One bout of high-intensity cardiovascular exercise performed immediately after practicing a motor skill promotes changes in the neuroplasticity of the motor cortex and facilitates motor learning in nondisabled individuals. To determine if a bout of exercise performed at high intensity is sufficient to induce neuroplastic changes and improve motor skill retention in patients with chronic stroke. Twenty-two patients with different levels of motor impairment were recruited. On the first session, the effects of a maximal graded exercise test on corticospinal and intracortical excitability were assessed from the affected and unaffected primary motor cortex representational area of a hand muscle with transcranial magnetic stimulation. On the second session, participants were randomly assigned to an exercise or a nonexercise control group. Immediately after practicing a motor task, the exercise group performed 15 minutes of high-intensity interval training while the control group rested. Twenty-four hours after motor practice all participants completed a test of the motor task to assess skill retention. The graded exercise test reduced interhemispheric imbalances in GABA A -mediated short-interval intracortical inhibition but changes in other markers of excitability were not statistically significant. The group that performed high-intensity interval training showed a better retention of the motor skill. The performance of a maximal graded exercise test triggers only modest neuroplastic changes in patients with chronic stroke. However, a single bout of high-intensity interval training performed immediately after motor practice improves skill retention, which could potentially accelerate motor recovery in these individuals.

High-Intensity Interval Training After Stroke: An Opportunity to Promote Functional Recovery, Cardiovascular Health, and Neuroplasticity.

PubMed

Crozier, Jennifer; Roig, Marc; Eng, Janice J; MacKay-Lyons, Marilyn; Fung, Joyce; Ploughman, Michelle; Bailey, Damian M; Sweet, Shane N; Giacomantonio, Nicholas; Thiel, Alexander; Trivino, Michael; Tang, Ada

2018-04-01

Stroke is the leading cause of adult disability. Individuals poststroke possess less than half of the cardiorespiratory fitness (CRF) as their nonstroke counterparts, leading to inactivity, deconditioning, and an increased risk of cardiovascular events. Preserving cardiovascular health is critical to lower stroke risk; however, stroke rehabilitation typically provides limited opportunity for cardiovascular exercise. Optimal cardiovascular training parameters to maximize recovery in stroke survivors also remains unknown. While stroke rehabilitation recommendations suggest the use of moderate-intensity continuous exercise (MICE) to improve CRF, neither is it routinely implemented in clinical practice, nor is the intensity always sufficient to elicit a training effect. High-intensity interval training (HIIT) has emerged as a potentially effective alternative that encompasses brief high-intensity bursts of exercise interspersed with bouts of recovery, aiming to maximize cardiovascular exercise intensity in a time-efficient manner. HIIT may provide an alternative exercise intervention and invoke more pronounced benefits poststroke. To provide an updated review of HIIT poststroke through ( a) synthesizing current evidence; ( b) proposing preliminary considerations of HIIT parameters to optimize benefit; ( c) discussing potential mechanisms underlying changes in function, cardiovascular health, and neuroplasticity following HIIT; and ( d) discussing clinical implications and directions for future research. Preliminary evidence from 10 studies report HIIT-associated improvements in functional, cardiovascular, and neuroplastic outcomes poststroke; however, optimal HIIT parameters remain unknown. Larger randomized controlled trials are necessary to establish ( a) effectiveness, safety, and optimal training parameters within more heterogeneous poststroke populations; (b) potential mechanisms of HIIT-associated improvements; and ( c) adherence and psychosocial outcomes.

Stress as a one-armed bandit: Differential effects of stress paradigms on the morphology, neurochemistry and behavior in the rodent amygdala

PubMed Central

Wilson, Marlene A.; Grillo, Claudia A.; Fadel, Jim R.; Reagan, Lawrence P.

2015-01-01

Neuroplasticity may be defined as the ability of the central nervous system (CNS) to respond to changes in the internal and external environment and it is well established that some stimuli have the ability to facilitate or impair neuroplasticity depending on the pre-existing milieu. A classic example of a stimulus that can both facilitate and impair neuroplasticity is stress. Indeed, the ability of CNS to respond to acute stress is often dependent upon the prior stress history of the individual. While responses to acute stress are often viewed as adaptive in nature, stress reactivity in subjects with prior chronic stress experiences are often linked to neuropsychiatric disorders, including major depressive disorder, post-traumatic stress disorder (PTSD) and anxiety. In rodent studies, chronic stress exposure produces structural and functional alterations in the hippocampus and medial prefrontal cortex that are consistent across different types of stress paradigms. Conversely, the amygdala appears to exhibit differential structural and functional responses to stress that are dependent on a variety of factors, including the type of stressor performed and the duration of the stress paradigm. This is most evident in output measures including morphological analysis of amygdala neurons, measurement of glutamatergic tone in amygdalar subdivisions and the analysis of amygdala-centric behaviors. Accordingly, this review will provide an overview of the effects of stress on the structural and functional plasticity of the rodent amygdala, especially in relation to the differential effects of repeated or chronic stress paradigms on dendritic architecture, neurochemistry of the glutamatergic system and behavior. PMID:26844236

Increase in PAS-induced neuroplasticity after a treatment course of intranasal ketamine for depression. Report of three cases from a placebo-controlled trial.

PubMed

Gálvez, Verònica; Nikolin, Stevan; Ho, Kerrie-Anne; Alonzo, Angelo; Somogyi, Andrew A; Loo, Colleen K

2017-02-01

Animal studies suggest that neural plasticity may play a role in the antidepressant effects of a single ketamine dose. However, the potential effects of repeated ketamine treatments on human neuroplasticity are unknown. This pilot RCT study measured plasticity-induced changes before and after a ketamine course, in three treatment-resistant depressed subjects, who were randomized to receive 8 intranasal treatments of 100mg ketamine or 4.5mg midazolam. Mood ratings were performed by a trained blinded rater at baseline and 24h-48h after the ketamine course, using the Montgomery Asberg Depression Rating Scale (MADRS). Neuroplasticity was assessed in the motor cortex using a paired associative stimulation (PAS) paradigm at baseline and 24h-48h after the treatment course. No changes in current psychotropic medication or dosage were permitted for 4weeks prior to trial entry and throughout the trial. The subject receiving ketamine, but not those receiving midazolam, presented a marked increase in neural plasticity after the treatment course. However, mood changes were not associated with changes in neural plasticity. Pilot study with small sample size. Concomitant antidepressant medications taken. Plasticity was tested in the motor cortex only, thus the generalizability of these findings to other brain areas cannot be assumed. These results suggest that a course of intranasal ketamine may enhance synaptic plasticity in subjects with depression, but this was not associated with antidepressant effects. Further research on this topic is warranted. Copyright © 2016 Elsevier Inc. All rights reserved.

Beet Root Juice: An Ergogenic Aid for Exercise and the Aging Brain.

PubMed

Petrie, Meredith; Rejeski, W Jack; Basu, Swati; Laurienti, Paul J; Marsh, Anthony P; Norris, James L; Kim-Shapiro, Daniel B; Burdette, Jonathan H

2017-09-01

Exercise has positive neuroplastic effects on the aging brain. It has also been shown that ingestion of beet root juice (BRJ) increases blood flow to the brain and enhances exercise performance. Here, we examined whether there are synergistic effects of BRJ and exercise on neuroplasticity in the aging brain. Peak metabolic equivalent (MET) capacity and resting-state magnetic resonance imaging functional brain network organization are reported on 26 older (mean age = 65.4 years) participants randomly assigned to 6 weeks of exercise + BRJ or exercise + placebo. Somatomotor community structure consistency was significantly enhanced in the exercise + BRJ group following the intervention (MBRJ = -2.27, SE = 0.145, MPlacebo = -2.89, SE = 0.156, p = .007). Differences in second-order connections between the somatomotor cortex and insular cortex were also significant; the exercise + BRJ group (M = 3.28, SE = 0.167) had a significantly lower number of connections than exercise + placebo (M = 3.91, SE = 0.18, p = .017) following the intervention. Evaluation of peak MET capacity revealed a trend for the exercise + BRJ group to have higher MET capacity following the intervention. Older adults who exercised and consumed BRJ demonstrated greater consistency within the motor community and fewer secondary connections with the insular cortex compared with those who exercised without BRJ. The exercise + BRJ group had brain networks that more closely resembled those of younger adults, showing the potential enhanced neuroplasticity conferred by combining exercise and BRJ consumption. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Neuroendocrine Actions of Organohalogens: Thyroid Hormones, Arginine Vasopressin, and Neuroplasticity

EPA Science Inventory

Organohalogen compounds are global environmental pollutants. They are highly persistent, bioaccumulative, and cause adverse effects in humans and wildlife. Because of the widespread use of these organohalogens in household items and consumer products, indoor contamination may be ...

Repetitive transcranial magnetic stimulation induces oscillatory power changes in chronic tinnitus

PubMed Central

Schecklmann, Martin; Lehner, Astrid; Gollmitzer, Judith; Schmidt, Eldrid; Schlee, Winfried; Langguth, Berthold

2015-01-01

Chronic tinnitus is associated with neuroplastic changes in auditory and non-auditory cortical areas. About 10 years ago, repetitive transcranial magnetic stimulation (rTMS) of auditory and prefrontal cortex was introduced as potential treatment for tinnitus. The resulting changes in tinnitus loudness are interpreted in the context of rTMS induced activity changes (neuroplasticity). Here, we investigate the effect of single rTMS sessions on oscillatory power to probe the capacity of rTMS to interfere with tinnitus-specific cortical plasticity. We measured 20 patients with bilateral chronic tinnitus and 20 healthy controls comparable for age, sex, handedness, and hearing level with a 63-channel electroencephalography (EEG) system. Educational level, intelligence, depressivity and hyperacusis were controlled for by analysis of covariance. Different rTMS protocols were tested: Left and right temporal and left and right prefrontal cortices were each stimulated with 200 pulses at 1 Hz and with an intensity of 60% stimulator output. Stimulation of central parietal cortex with 6-fold reduced intensity (inverted passive-cooled coil) served as sham condition. Before and after each rTMS protocol 5 min of resting state EEG were recorded. The order of rTMS protocols was randomized over two sessions with 1 week interval in between. Analyses on electrode level showed that people with and without tinnitus differed in their response to left temporal and right frontal stimulation. In tinnitus patients left temporal rTMS decreased frontal theta and delta and increased beta2 power, whereas right frontal rTMS decreased right temporal beta3 and gamma power. No changes or increases were observed in the control group. Only non-systematic changes in tinnitus loudness were induced by single sessions of rTMS. This is the first study to show tinnitus-related alterations of neuroplasticity that were specific to stimulation site and oscillatory frequency. The observed effects can be interpreted within the thalamocortical dysrhythmia model assuming that slow waves represent processes of deafferentiation and that high frequencies might be indicators for tinnitus loudness. Moreover our findings confirm the role of the left temporal and the right frontal areas as relevant hubs in tinnitus related neuronal network. Our results underscore the value of combined TMS-EEG measurements for investigating disease related changes in neuroplasticity. PMID:26557055

Therapeutic drug approach to stimulate clinical recovery after brain injury.

PubMed

Krieger, Derk W

2013-01-01

The identification of strategies by which the central nervous system (CNS) can transform itself in response to injury has incited the systematic exploration of methods to enhance neurological recovery after CNS injury. Several pharmaceuticals have been shown to promote such recovery; however, more rigorous clinical trials are necessary to establish their clinical relevance. The major impediment for these strategies in the clinical arena is the astounding heterogeneity surrounding neuroplasticity and regeneration. Tolerance to injury and varied rates of recovery are likely governed by genetic and environmental factors that remain largely elusive. The extraordinary complexity of the neural networks in the CNS impedes the assessment of 'plain' pharmacological interventions in therapeutic trials. 'Proof-of-principle' studies of pharmacological interventions enhancing neuroplasticity or regeneration may therefore at first focus on surrogate markers, such as functional MRI, magnetoencephalography and diffusion tensor imaging, or investigate seemingly more uniform systems, such as spinal cord injuries. The discovery that experimental adult CNS lesions can essentially regenerate has rejected the conviction that adult axon injury is always permanent and spurred research into determining whether the circumstances under which such regeneration occurs can be created in human CNS injury. The hostility of the microenvironment preventing axonal regrowth has been linked to key molecular targets involving myelin-associated factors and glial scar components. While the mechanisms involved are better understood now and potential therapeutic targets are identified, the crucial question whether manipulating the molecular regulation of axonal repair is feasible and will benefit patients remains uncertain. While factual repair of brain tissue may still be years away, research into the mechanisms of adaptation after brain injury offers more tangible return on the short run. Copyright © 2013 S. Karger AG, Basel.

The role of brain extracellular proteins in neuroplasticity and learning.

PubMed

Shashoua, V E

1985-06-01

Double labeling studies of the pattern of protein synthesis in goldfish and mouse brain identified a class of glycoproteins (the ependymins) whose turnover rate was enhanced after training. A variety of control experiments indicated that these macromolecules have an important role in the molecular and cell biology of learning. Antisera to the ependymins when injected into the brains of trained goldfish cause amnesia of a newly acquired behavior. Isolation and localization studies by immunocytochemical methods indicate that the ependymins are released into the brain extracellular fluid by a class of neurosecretory cells. In mammalian brain ependymin-containing cells are highly concentrated in the limibic system. The ependymins are constituted from two disulfide-linked acidic polypeptide chains (M.W.37K and 31K). They contain at least 5% covalently bound carbohydrate per chain with mannose, galactose, N-acetylglucosamine and N-acetylneuraminic acid as the predominant components. The highly soluble ependymins can rapidly polymerize to form an insoluble fibrous matrix if calcium is removed from solution by the addition of a Ca2+-chelating agent or dialysis. The self-aggregation property of the ependymins can be triggered by the depletion of Ca2+ from the extracellular space. Studies of the kinetics of the aggregation phenomenon by measurements of turbidity changes indicate that the process can be terminated but not reversed by restoring Ca2+ to its normal CSF level. Immunohistochemical studies of the brains of trained goldfish show the presence of punctate statining sites in the perimeter of certain cells located in specific brain regions. This suggests that ependymin aggregation might occur in vivo during learning. A molecular hypothesis relating the aggregation properties of the ependymins to neuroplasticity and learning is proposed.

Cingulo-insular structural alterations associated with psychogenic symptoms, childhood abuse and PTSD in functional neurological disorders.

PubMed

Perez, David L; Matin, Nassim; Barsky, Arthur; Costumero-Ramos, Victor; Makaretz, Sara J; Young, Sigrid S; Sepulcre, Jorge; LaFrance, W Curt; Keshavan, Matcheri S; Dickerson, Bradford C

2017-06-01

Adverse early-life events are predisposing factors for functional neurological disorder (FND) and post-traumatic stress disorder (PTSD). Cingulo-insular regions are implicated in the biology of both conditions and are sites of stress-mediated neuroplasticity. We hypothesised that functional neurological symptoms and the magnitude of childhood abuse would be associated with overlapping anterior cingulate cortex (ACC) and insular volumetric reductions, and that FND and PTSD symptoms would map onto distinct cingulo-insular areas. This within-group voxel-based morphometry study probes volumetric associations with self-report measures of functional neurological symptoms, adverse life events and PTSD symptoms in 23 mixed-gender FND patients. Separate secondary analyses were also performed in the subset of 18 women with FND to account for gender-specific effects. Across the entire cohort, there were no statistically significant volumetric associations with self-report measures of functional neurological symptom severity or childhood abuse. In women with FND, however, parallel inverse associations were observed between left anterior insular volume and functional neurological symptoms as measured by the Patient Health Questionnaire-15 and the Screening for Somatoform Symptoms Conversion Disorder subscale. Similar inverse relationships were also appreciated between childhood abuse burden and left anterior insular volume. Across all subjects, PTSD symptom severity was inversely associated with dorsal ACC volume, and the magnitude of lifetime adverse events was inversely associated with left hippocampal volume. This study reveals distinct cingulo-insular alterations for FND and PTSD symptoms and may advance our understanding of FND. Potential biological convergence between stress-related neuroplasticity, functional neurological symptoms and reduced insular volume was identified. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Neuroplastic Response After Radiation Therapy for Pediatric Brain Tumors: A Pilot Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Armstrong, Carol L., E-mail: armstrongc@email.chop.edu; Fisher, Michael J.; Li, Yimei

Purpose: Clinically effective measurement of cognitive toxicity from photon radiation therapy (XRT) should be accurate, sensitive, and specific. This pilot study tested translational findings on phasic changes in children's memory systems that are sensitive and insensitive to toxic XRT effects to identify a possible neuroplastic effect. Methods and Materials: Memory processes were prospectively tested before XRT and at 3 later time points up to 2 years in 35 children with mixed primary brain tumors who had not experienced recurrence. Memory processes were verbal-semantic, visual-semantic, and visual-perceptual, including accuracy, speed to recall, encoding, retrieval, and recognition. The mixed-effects model included time (tomore » estimate slope), covariates (age, tumor locus, XRT field, and medications) as fixed effects, and individual random intercepts. A sensitivity analysis examined the influence of XRT dose to the hippocampi on memory. Results: Retrieval from long-term verbal-semantic memory declined 2 months after completing XRT, as seen in adults, and was lowest at 1 year, which was delayed in comparison with adults. Double dissociation from visual-perceptual memory at baseline and 2 months was found, consistent with adults. Recovery was demonstrated 2 years after XRT. Patterns were unchanged when dose to hippocampus was included in the model. Conclusions: Verbal and semantic long-term retrieval is specifically sensitive to XRT-related cognitive dysfunction, without effect on visual-perceptual memory. Children reached nadir in XRT-sensitive memory 1 year after XRT and recovered by 2 years, which is later than that observed in adults. The protracted period of post-XRT injury may represent the maturation of the human hippocampus and white matter into late adolescence.« less

Adaptive and pathological inhibition of neuroplasticity associated with circadian rhythms and sleep.

PubMed

Heller, H Craig; Ruby, Norman F; Rolls, Asya; Makam, Megha; Colas, Damien

2014-06-01

The circadian system organizes sleep and wake through imposing a daily cycle of sleep propensity on the organism. Sleep has been shown to play an important role in learning and memory. Apart from the daily cycle of sleep propensity, however, direct effects of the circadian system on learning and memory also have been well documented. Many mechanistic components of the memory consolidation process ranging from the molecular to the systems level have been identified and studied. The question that remains is how do these various processes and components work together to produce cycles of increased and decreased learning abilities, and why should there be times of day when neural plasticity appears to be restricted? Insights into this complex problem can be gained through investigations of the learning disabilities caused by circadian disruption in Siberian hamsters and by aneuploidy in Down's syndrome mice. A simple working hypothesis that has been explored in this work is that the observed learning disabilities are due to an altered excitation/inhibition balance in the CNS. Excessive inhibition is the suspected cause of deficits in memory consolidation. In this article we present the evidence that excessive inhibition in these cases of learning disability involves GABAergic neurotransmission, that treatment with GABA receptor inhibitors can reverse the learning disability, and that the efficacy of the treatment is time sensitive coincident with the major daily sleep phase, and that it depends on sleep. The evidence we present leads us to hypothesize that a function of the circadian system is to reduce neuroplasticity during the daily sleep phase when processes of memory consolidation are taking place. PsycINFO Database Record (c) 2014 APA, all rights reserved.

The State-of-the-Science on Somatosensory Function and Its Impact on Daily Life in Adults and Older Adults, and Following Stroke: A Scoping Review.

PubMed

Carey, Leeanne M; Lamp, Gemma; Turville, Megan

2016-04-01

The aim was to identify and synthesize research evidence about how adults and older adults process somatosensory information in daily activities, and the interventions available to regain somatosensory function following stroke. We developed two interacting concept maps to address the research questions. The scoping review was conducted from 2005 to 2015 across Web of Science, AMED, CINAHL, Embase, Medline, and PsychInfo databases. Search terms included somatosensory, perception, performance, participation, older adult, stroke, intervention, discrimination, learning, and neuroplasticity. Contributions from 103 articles for Concept 1 and 14 articles for Concept 2 are reported. Measures of somatosensory processing, performance, and participation used are identified. Interventions available to treat somatosensory loss are summarized in relation to approach, outcome measures, and theory/mechanisms underlying. A gap exists in the current understanding of how somatosensory function affects the daily lives of adults. A multidisciplinary approach that includes performance and participation outcomes is recommended to advance the field. © The Author(s) 2016.

Experiences with Bilateral Art: A Retrospective Study

ERIC Educational Resources Information Center

McNamee, Carole M.

2006-01-01

Recent advances in neuroscience describe the effect of experience on neural architecture. Paralleling these advances in neuroscience, recent explorations in the field of art therapy speculate on the relationship between specific therapeutic interventions and neuroplasticity, which underlies the changes in neural architecture. One such…

Modulation of neuroplasticity pathways and antidepressant-like behavioural responses following the short-term (3 and 7 days) administration of the 5-HT₄ receptor agonist RS67333.

PubMed

Pascual-Brazo, Jesús; Castro, Elena; Díaz, Alvaro; Valdizán, Elsa M; Pilar-Cuéllar, Fuencisla; Vidal, Rebeca; Treceño, Begoña; Pazos, Angel

2012-06-01

It has been recently suggested that activation of 5-HT₄ receptors might exert antidepressant-like effects in rats after 3 d treatment, suggesting a new strategy for developing faster-acting antidepressants. We studied the effects of 3 d and 7 d treatment with the 5-HT₄ receptor partial agonist RS67333 (1.5 mg/kg.d) in behavioural tests of chronic efficacy and on neuroplastic-associated changes, such as adult hippocampal neurogenesis, expression of CREB, BDNF, β-catenin, AKT and 5-HT₄ receptor functionality. RS67333 treatment up-regulated hippocampal cell proliferation, β-catenin expression and pCREB/CREB ratio after 3 d treatment. This short-term treatment also reduced immobility time in the forced swim test (FST), together with a partial reversion of the anhedonic-like state (sucrose consumption after chronic corticosterone). Administration of RS67333 for 7 d resulted in a higher increase in the rate of hippocampal cell proliferation, a significant desensitization of 5-HT₄ receptor-coupled adenylate cyclase activity and a more marked increase in the expression of neuroplasticity-related proteins (BDNF, CREB, AKT): these changes reached the same magnitude as those observed after 3 wk administration of classical antidepressants. Consistently, a positive behavioural response in the novelty suppressed feeding (NSF) test and a complete reversion of the anhedonic-like state (sucrose consumption) were also observed after 7 d treatment. These results support the antidepressant-like profile of RS67333 with a shorter onset of action and suggest that this time period of administration (3-7 d) could be a good approximation to experimentally predict the onset of action of this promising strategy.

Dissociation of thirst and sodium appetite in the furo/cap model of extracellular dehydration and a role for N-methyl-D-aspartate receptors in the sensitization of sodium appetite

PubMed Central

Hurley, Seth. W.; Johnson, Alan Kim

2015-01-01

Depletion of extracellular fluids motivates many animals to seek out and ingest water and sodium. Animals with a history of extracellular dehydration display enhanced sodium appetite and in some cases thirst. The progressive increase in sodium intake induced by repeated sodium depletions is known as sensitization of sodium appetite. Administration of the diuretic and natriuretic drug, furosemide, along with a low dose of captopril (furo/cap), elicits thirst and a rapid onset of sodium appetite. In the present studies the furo/cap model was used to explore the physiological mechanisms of sensitization of sodium appetite. However, when thirst and sodium appetite were measured concurrently in the furo/cap model, individual rats exhibited sensitization of either thirst or sodium appetite. In subsequent studies, thirst and sodium appetite were dissociated by offering either water prior to sodium or sodium before water. When water and sodium intake were dissociated in time, the furo/cap model reliably produced sensitization of sodium appetite. It is likely that neuroplasticity mediates this sensitization. Glutamatergic N-methyl-d-aspartate receptor (NMDA-R) activation is critical for the development of most forms of neuroplasticity. Therefore, we hypothesized that integrity of NMDA-R function is necessary for the sensitization of sodium appetite. Pharmacological blockade of NMDA-Rs with systemic administration of MK-801 (0.15mg/kg) prevented the sensitization of fluid intake in general when water and sodium were offered concurrently, and prevented sensitization of sodium intake specifically when water and sodium intake were dissociated. The involvement of NMDA-Rs provides support for the possibility that sensitization of sodium appetite is mediated by neuroplasticity. PMID:24341713

Val66Met BDNF polymorphism as a vulnerability factor for inflammation-associated depressive symptoms in women with breast cancer

PubMed Central

Dooley, Larissa N.; Ganz, Patricia A.; Cole, Steve W.; Crespi, Catherine M.; Bower, Julienne E.

2016-01-01

Background Inflammation contributes to the development of depression in a subset of individuals, but risk factors that render certain individuals vulnerable to inflammation-associated depression are undetermined. Drawing from animal studies showing that reduced neuroplasticity mediates effects of inflammation on depression, we hypothesized that individuals genetically predisposed to lower levels of neuroplasticity would be more susceptible to inflammation-associated depression. The current study examined whether the Met allele of the BDNF Val66met polymorphism, which predisposes individuals to reduced levels of brain-derived neurotrophic factor (BDNF), a protein vital for neuroplasticity, moderates the association between inflammation and depressive symptoms. Methods Our sample was 112 women with early-stage breast cancer who had recently completed cancer treatment, which can activate inflammation. Participants provided blood for genotyping and assessment of circulating inflammatory markers, and completed a questionnaire assessing depressive symptoms, including somatic, affective, and cognitive dimensions. Results There was a significant interaction between C-reactive protein (CRP) and the BDNF Val66met polymorphism in predicting cognitive depressive symptoms (p=.004), such that higher CRP was related to more cognitive depressive symptoms among Met allele carriers, but not among Val/Val homozygotes. Post-hoc longitudinal analyses suggested that, for Met carriers, higher CRP at baseline predicted higher cognitive depressive symptoms across a one-year follow-up period (p<.001). Conclusion The BDNF Met allele may be a risk factor for inflammation-associated cognitive depressive symptoms among breast cancer survivors. Women with breast cancer who carry this genotype may benefit from early identification and treatment. Limitation BDNF genotype is an indirect measure of BDNF protein levels. PMID:26967918

Class I Histone Deacetylase Inhibition by Tianeptinaline Modulates Neuroplasticity and Enhances Memory.

PubMed

Zhao, Wen-Ning; Ghosh, Balaram; Tyler, Marshall; Lalonde, Jasmin; Joseph, Nadine F; Kosaric, Nina; Fass, Daniel M; Tsai, Li-Huei; Mazitschek, Ralph; Haggarty, Stephen J

2018-06-22

Through epigenetic and other regulatory functions, the histone deacetylase (HDAC) family of enzymes has emerged as a promising therapeutic target for central nervous system and other disorders. Here we report on the synthesis and functional characterization of new HDAC inhibitors based structurally on tianeptine, a drug used primarily to treat major depressive disorder (MDD) that has a poorly understood mechanism of action. Since the chemical structure of tianeptine resembles certain HDAC inhibitors, we profiled the in vitro HDAC inhibitory activity of tianeptine and demonstrated its ability to inhibit the lysine deacetylase activity of a subset of class I HDACs. Consistent with a model of active site Zn 2+ chelation by the carboxylic acid present in tianeptine, newly synthesized analogues containing either a hydroxamic acid or ortho-aminoanilide exhibited increased potency and selectivity among the HDAC family. This in vitro potency translated to improved efficacy in a panel of high-content imaging assays designed to assess HDAC target engagement and functional effects on critical pathways involved in neuroplasticity in both primary mouse neurons and, for the first time, human neurons differentiated from pluripotent stem cells. Most notably, tianeptinaline, a class I HDAC-selective analogue of tianeptine, but not tianeptine itself, increased histone acetylation, and enhanced CREB-mediated transcription and the expression of Arc (activity-regulated cytoskeleton-associated protein). Systemic in vivo administration of tianeptinaline to mice confirmed its brain penetration and was found to enhance contextual fear conditioning, a behavioral test of hippocampal-dependent memory. Tianeptinaline and its derivatives provide new pharmacological tools to dissect chromatin-mediated neuroplasticity underlying memory and other epigenetically related processes implicated in health and disease.

CNS neuroplasticity and salt-sensitive hypertension induced by prior treatment with subpressor doses of ANG II or aldosterone.

PubMed

Clayton, Sarah C; Zhang, Zhongming; Beltz, Terry; Xue, Baojian; Johnson, Alan Kim

2014-06-15

Although sensitivity to high dietary NaCl is regarded to be a risk factor for cardiovascular disease, the causes of salt-sensitive hypertension remain elusive. Previously, we have shown that rats pretreated with subpressor doses of either ANG II or aldosterone (Aldo) show sensitized hypertensive responses to a mild pressor dose of ANG II when tested after an intervening delay. The current studies investigated whether such treatments will induce salt sensitivity. In studies employing an induction-delay-expression experimental design, male rats were instrumented for chronic mean arterial pressure (MAP) recording. In separate experiments, ANG II, Aldo, or vehicle was delivered either subcutaneously or intracerebroventricularly during the induction. There were no sustained differences in BP during the delay prior to being given 2% saline. While consuming 2% saline during the expression, both ANG II- and Aldo-pretreated rats showed significantly greater hypertension. When hexamethonium was used to assess autonomic control of MAP, no differences in the decrease of MAP in response to ganglionic blockade were detected during the induction. However, during the expression, the fall was greater in sensitized rats. In separate experiments, brain tissue that was collected at the end of delay showed increases in message or activation of putative markers of neuroplasticity (i.e., brain-derived neurotrophic factor, p38 mitogen-activated protein kinase, and cAMP response element-binding protein). These experiments demonstrate that prior administration of nonpressor doses of either ANG II or Aldo will induce salt sensitivity. Collectively, our findings indicate that treatment with subpressor doses of ANG II and Aldo initiate central neuroplastic changes that are involved in hypertension of different etiologies. Copyright © 2014 the American Physiological Society.

Peripheral and central changes combine to induce motor behavioral deficits in a moderate repetition task

PubMed Central

Coq, Jacques-Olivier; Barr, Ann E; Strata, Fabrizio; Russier, Michael; Kietrys, David M; Merzenich, Michael M; Byl, Nancy N; Barbe, Mary F

2009-01-01

Repetitive motion disorders, such as carpal tunnel syndrome and focal hand dystonia, can be associated with tasks that require prolonged, repetitive behaviors. Previous studies using animal models of repetitive motion have correlated cortical neuroplastic changes or peripheral tissue inflammation with fine motor performance. However, the possibility that both peripheral and central mechanisms coexist with altered motor performance has not been studied. In this study, we investigated the relationship between motor behaviour changes associated with repetitive behaviors and both peripheral tissue inflammation and cortical neuroplasticity. A rat model of reaching and grasping involving moderate repetitive reaching with negligible force (MRNF) was used. Rats performed the MRNF task for 2 hrs/day, 3 days/wk for 8 weeks. Reach performance was monitored by measuring reach rate/success, daily exposure, reach movement reversals/patterns, reach/grasp phase times, grip strength and grooming function. With cumulative task exposure, reach performance, grip strength and agility declined while an inefficient food retrieval pattern increased. In S1 of MRNF rats, a dramatic disorganization of the topographic forepaw representation was observed, including the emergence of large receptive fields located on both the wrist/forearm and forepaw with alterations of neuronal properties. In M1, there was a drastic enlargement of the overall forepaw map area, and of the cortex devoted to digit, arm-digits and elbow-wrist responses. In addition, unusually low current amplitude evoked digit movements. IL-1β and TNF-α increased in forearm flexor muscles and tendons of MRNF animals. The increases in IL-1β and TNF-α negatively correlated with grip strength and amount of current needed to evoke forelimb movements. This study provides strong evidence that both peripheral inflammation and cortical neuroplasticity jointly contribute to the development of chronic repetitive motion disorders. PMID:19686738

A Human-machine-interface Integrating Low-cost Sensors with a Neuromuscular Electrical Stimulation System for Post-stroke Balance Rehabilitation.

PubMed

Kumar, Deepesh; Das, Abhijit; Lahiri, Uttama; Dutta, Anirban

2016-04-12

A stroke is caused when an artery carrying blood from heart to an area in the brain bursts or a clot obstructs the blood flow to brain thereby preventing delivery of oxygen and nutrients. About half of the stroke survivors are left with some degree of disability. Innovative methodologies for restorative neurorehabilitation are urgently required to reduce long-term disability. The ability of the nervous system to reorganize its structure, function and connections as a response to intrinsic or extrinsic stimuli is called neuroplasticity. Neuroplasticity is involved in post-stroke functional disturbances, but also in rehabilitation. Beneficial neuroplastic changes may be facilitated with non-invasive electrotherapy, such as neuromuscular electrical stimulation (NMES) and sensory electrical stimulation (SES). NMES involves coordinated electrical stimulation of motor nerves and muscles to activate them with continuous short pulses of electrical current while SES involves stimulation of sensory nerves with electrical current resulting in sensations that vary from barely perceivable to highly unpleasant. Here, active cortical participation in rehabilitation procedures may be facilitated by driving the non-invasive electrotherapy with biosignals (electromyogram (EMG), electroencephalogram (EEG), electrooculogram (EOG)) that represent simultaneous active perception and volitional effort. To achieve this in a resource-poor setting, e.g., in low- and middle-income countries, we present a low-cost human-machine-interface (HMI) by leveraging recent advances in off-the-shelf video game sensor technology. In this paper, we discuss the open-source software interface that integrates low-cost off-the-shelf sensors for visual-auditory biofeedback with non-invasive electrotherapy to assist postural control during balance rehabilitation. We demonstrate the proof-of-concept on healthy volunteers.

Peripheral and central changes combine to induce motor behavioral deficits in a moderate repetition task.

PubMed

Coq, Jacques-Olivier; Barr, Ann E; Strata, Fabrizio; Russier, Michael; Kietrys, David M; Merzenich, Michael M; Byl, Nancy N; Barbe, Mary F

2009-12-01

Repetitive motion disorders, such as carpal tunnel syndrome and focal hand dystonia, can be associated with tasks that require prolonged, repetitive behaviors. Previous studies using animal models of repetitive motion have correlated cortical neuroplastic changes or peripheral tissue inflammation with fine motor performance. However, the possibility that both peripheral and central mechanisms coexist with altered motor performance has not been studied. In this study, we investigated the relationship between motor behavior changes associated with repetitive behaviors and both peripheral tissue inflammation and cortical neuroplasticity. A rat model of reaching and grasping involving moderate repetitive reaching with negligible force (MRNF) was used. Rats performed the MRNF task for 2 h/day, 3 days/week for 8 weeks. Reach performance was monitored by measuring reach rate/success, daily exposure, reach movement reversals/patterns, reach/grasp phase times, grip strength and grooming function. With cumulative task exposure, reach performance, grip strength and agility declined while an inefficient food retrieval pattern increased. In S1 of MRNF rats, a dramatic disorganization of the topographic forepaw representation was observed, including the emergence of large receptive fields located on both the wrist/forearm and forepaw with alterations of neuronal properties. In M1, there was a drastic enlargement of the overall forepaw map area, and of the cortex devoted to digit, arm-digits and elbow-wrist responses. In addition, unusually low current amplitude evoked digit movements. IL-1 beta and TNF-alpha increased in forearm flexor muscles and tendons of MRNF animals. The increases in IL-1 beta and TNF-alpha negatively correlated with grip strength and amount of current needed to evoke forelimb movements. This study provides strong evidence that both peripheral inflammation and cortical neuroplasticity jointly contribute to the development of chronic repetitive motion disorders.

Induction of late LTP-like plasticity in the human motor cortex by repeated non-invasive brain stimulation.

PubMed

Monte-Silva, Katia; Kuo, Min-Fang; Hessenthaler, Silvia; Fresnoza, Shane; Liebetanz, David; Paulus, Walter; Nitsche, Michael A

2013-05-01

Non-invasive brain stimulation enables the induction of neuroplasticity in humans, however, with so far restricted duration of the respective cortical excitability modifications. Conventional anodal transcranial direct current stimulation (tDCS) protocols including one stimulation session induce NMDA receptor-dependent excitability enhancements lasting for about 1 h. We aimed to extend the duration of tDCS effects by periodic stimulation, consisting of two stimulation sessions, since periodic stimulation protocols are able to induce neuroplastic excitability alterations stable for days or weeks, termed late phase long term potentiation (l-LTP), in animal slice preparations. Since both, l-LTP and long term memory formation, require gene expression and protein synthesis, and glutamatergic receptor activity modifications, l-LTP might be a candidate mechanism for the formation of long term memory. The impact of two consecutive tDCS sessions on cortical excitability was probed in the motor cortex of healthy humans, and compared to that of a single tDCS session. The second stimulation was applied without an interval (temporally contiguous tDCS), during the after-effects of the first stimulation (during after-effects; 3, or 20 min interval), or after the after-effects of the first stimulation had vanished (post after-effects; 3 or 24 h interval). The during after-effects condition resulted in an initially reduced, but then relevantly prolonged excitability enhancement, which was blocked by an NMDA receptor antagonist. The other conditions resulted in an abolishment, or a calcium channel-dependent reversal of neuroplasticity. Repeated tDCS within a specific time window is able to induce l-LTP-like plasticity in the human motor cortex. Copyright © 2013 Elsevier Inc. All rights reserved.

Theta/beta neurofeedback in children with ADHD: Feasibility of a short-term setting and plasticity effects.

PubMed

Van Doren, Jessica; Heinrich, Hartmut; Bezold, Mareile; Reuter, Nina; Kratz, Oliver; Horndasch, Stefanie; Berking, Matthias; Ros, Tomas; Gevensleben, Holger; Moll, Gunther H; Studer, Petra

2017-02-01

Neurofeedback (NF) is increasingly used as a therapy for attention-deficit/hyperactivity disorder (ADHD), however behavioral improvements require 20 plus training sessions. More economic evaluation strategies are needed to test methodological optimizations and mechanisms of action. In healthy adults, neuroplastic effects have been demonstrated directly after a single session of NF training. The aim of our study was to test the feasibility of short-term theta/beta NF in children with ADHD and to learn more about the mechanisms underlying this protocol. Children with ADHD conducted two theta/beta NF sessions. In the first half of the sessions, three NF trials (puzzles as feedback animations) were run with pre- and post-reading and picture search tasks. A significant decrease of the theta/beta ratio (TBR), driven by a decrease of theta activity, was found in the NF trials of the second session demonstrating rapid and successful neuroregulation by children with ADHD. For pre-post comparisons, children were split into good vs. poor regulator groups based on the slope of their TBR over the NF trials. For the reading task, significant EEG changes were seen for the theta band from pre- to post-NF depending on individual neuroregulation ability. This neuroplastic effect was not restricted to the feedback electrode Cz, but appeared as a generalized pattern, maximal over midline and right-hemisphere electrodes. Our findings indicate that short-term NF may be a valuable and economical tool to study the neuroplastic mechanisms of targeted NF protocols in clinical disorders, such as theta/beta training in children with ADHD. Copyright © 2016 Elsevier B.V. All rights reserved.

Calbindin-D28k and calretinin in chicken inner retina during postnatal development and neuroplasticity by dim red light.

PubMed

Fosser, Nicolás Sebastián; Ronco, Laura; Bejarano, Alejandro; Paganelli, Alejandra R; Ríos, Hugo

2013-07-01

Members of the family of calcium binding proteins (CBPs) are involved in the buffering of calcium (Ca2+) by regulating how Ca2+ can operate within synapses or more globally in the entire cytoplasm and they are present in a particular arrangement in all types of retinal neurons. Calbindin D28k and calretinin belong to the family of CBPs and they are mainly co-expressed with other CBPs. Calbindin D28k is expressed in doubles cones, bipolar cells and in a subpopulation of amacrine and ganglion neurons. Calretinin is present in horizontal cells as well as in a subpopulation of amacrine and ganglion neurons. Both proteins fill the soma at the inner nuclear layer and the neuronal projections at the inner plexiform layer. Moreover, calbindin D28k and calretinin have been associated with neuronal plasticity in the central nervous system. During pre and early postnatal visual development, the visual system shows high responsiveness to environmental influences. In this work we observed modifications in the pattern of stratification of calbindin immunoreactive neurons, as well as in the total amount of calbindin through the early postnatal development. In order to test whether or not calbindin is involved in retinal plasticity we analyzed phosphorylated p38 MAPK expression, which showed a decrease in p-p38 MAPK, concomitant to the observed decrease of calbindin D28k. Results showed in this study suggest that calbindin is a molecule related with neuroplasticity, and we suggest that calbindin D28k has significant roles in neuroplastic changes in the retina, when retinas are stimulated with different light conditions. Copyright © 2013 Wiley Periodicals, Inc.

A Human-machine-interface Integrating Low-cost Sensors with a Neuromuscular Electrical Stimulation System for Post-stroke Balance Rehabilitation

PubMed Central

Kumar, Deepesh; Das, Abhijit; Lahiri, Uttama; Dutta, Anirban

2016-01-01

A stroke is caused when an artery carrying blood from heart to an area in the brain bursts or a clot obstructs the blood flow to brain thereby preventing delivery of oxygen and nutrients. About half of the stroke survivors are left with some degree of disability. Innovative methodologies for restorative neurorehabilitation are urgently required to reduce long-term disability. The ability of the nervous system to reorganize its structure, function and connections as a response to intrinsic or extrinsic stimuli is called neuroplasticity. Neuroplasticity is involved in post-stroke functional disturbances, but also in rehabilitation. Beneficial neuroplastic changes may be facilitated with non-invasive electrotherapy, such as neuromuscular electrical stimulation (NMES) and sensory electrical stimulation (SES). NMES involves coordinated electrical stimulation of motor nerves and muscles to activate them with continuous short pulses of electrical current while SES involves stimulation of sensory nerves with electrical current resulting in sensations that vary from barely perceivable to highly unpleasant. Here, active cortical participation in rehabilitation procedures may be facilitated by driving the non-invasive electrotherapy with biosignals (electromyogram (EMG), electroencephalogram (EEG), electrooculogram (EOG)) that represent simultaneous active perception and volitional effort. To achieve this in a resource-poor setting, e.g., in low- and middle-income countries, we present a low-cost human-machine-interface (HMI) by leveraging recent advances in off-the-shelf video game sensor technology. In this paper, we discuss the open-source software interface that integrates low-cost off-the-shelf sensors for visual-auditory biofeedback with non-invasive electrotherapy to assist postural control during balance rehabilitation. We demonstrate the proof-of-concept on healthy volunteers. PMID:27166666

Introducing graph theory to track for neuroplastic alterations in the resting human brain: a transcranial direct current stimulation study.

PubMed

Polanía, Rafael; Paulus, Walter; Antal, Andrea; Nitsche, Michael A

2011-02-01

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that alters cortical excitability and activity in a polarity-dependent way. Stimulation for a few minutes has been shown to induce plastic alterations of cortical excitability and to improve cognitive performance. These effects might be related to stimulation-induced alterations of functional cortical network connectivity. We aimed to investigate the impact of tDCS on cortical network function by functional connectivity and graph theoretical analysis of the BOLD fMRI spontaneous activity. fMRI resting-state datasets were acquired immediately before and after 10-min bipolar tDCS during rest, with the anode placed over the left primary motor cortex (M1) and the cathode over the contralateral frontopolar cortex. For each dataset, grey matter voxel-based synchronization matrices were calculated and thresholded to construct undirected graphs. Nodal connectivity degree and minimum path length maps were calculated and compared before and after tDCS. Nodal minimum path lengths significantly increased in the left somatomotor (SM1) cortex after anodal tDCS, which means that the number of direct functional connections from the left SM1 to topologically distant grey matter voxels significantly decreased. In contrast, functional coupling between premotor and superior parietal areas with the left SM1 significantly increased. Additionally, the nodal connectivity degree in the left posterior cingulate cortex (PCC) area as well as in the right dorsolateral prefrontal cortex (right DLPFC) significantly increased. In summary, we provide initial support that tDCS-induced neuroplastic alterations might be related to functional connectivity changes in the human brain. Additionally, we propose our approach as a powerful method to track for neuroplastic changes in the human brain. Copyright © 2010 Elsevier Inc. All rights reserved.

In SilicoModel-driven Assessment of the Effects of Brain-derived Neurotrophic Factor Deficiency on Glutamate and Gamma-Aminobutyric Acid: Implications for Understanding Schizophrenia Pathophysiology.

PubMed

Agrawal, Rimjhim; Kalmady, Sunil Vasu; Venkatasubramanian, Ganesan

2017-05-31

Deficient brain-derived neurotrophic factor (BDNF) is one of the important mechanisms underlying the neuroplasticity abnormalities in schizophrenia. Aberration in BDNF signaling pathways directly or circuitously influences neurotransmitters like glutamate and gamma-aminobutyric acid (GABA). For the first time, this study attempts to construct and simulate the BDNF-neurotransmitter network in order to assess the effects of BDNF deficiency on glutamate and GABA. Using CellDesigner, we modeled BDNF interactions with calcium influx via N-methyl-D-aspartate receptor (NMDAR)- Calmodulin activation; synthesis of GABA via cell cycle regulators protein kinase B, glycogen synthase kinase and β-catenin; transportation of glutamate and GABA. Steady state stability, perturbation time-course simulation and sensitivity analysis were performed in COPASI after assigning the kinetic functions, optimizing the unknown parameters using random search and genetic algorithm. Study observations suggest that increased glutamate in hippocampus, similar to that seen in schizophrenia, could potentially be contributed by indirect pathway originated from BDNF. Deficient BDNF could suppress Glutamate decarboxylase 67-mediated GABA synthesis. Further, deficient BDNF corresponded to impaired transport via vesicular glutamate transporter, thereby further increasing the intracellular glutamate in GABAergic and glutamatergic cells. BDNF also altered calcium dependent neuroplasticity via NMDAR modulation. Sensitivity analysis showed that Calmodulin, cAMP response element-binding protein (CREB) and CREB regulated transcription coactivator-1 played significant role in this network. The study presents in silico quantitative model of biochemical network constituting the key signaling molecules implicated in schizophrenia pathogenesis. It provides mechanistic insights into putative contribution of deficient BNDF towards alterations in neurotransmitters and neuroplasticity that are consistent with current understanding of the disorder.

In Silico Model-driven Assessment of the Effects of Brain-derived Neurotrophic Factor Deficiency on Glutamate and Gamma-Aminobutyric Acid: Implications for Understanding Schizophrenia Pathophysiology

PubMed Central

Agrawal, Rimjhim; Kalmady, Sunil Vasu; Venkatasubramanian, Ganesan

2017-01-01

Objective Deficient brain-derived neurotrophic factor (BDNF) is one of the important mechanisms underlying the neuroplasticity abnormalities in schizophrenia. Aberration in BDNF signaling pathways directly or circuitously influences neurotransmitters like glutamate and gamma-aminobutyric acid (GABA). For the first time, this study attempts to construct and simulate the BDNF-neurotransmitter network in order to assess the effects of BDNF deficiency on glutamate and GABA. Methods Using CellDesigner, we modeled BDNF interactions with calcium influx via N-methyl-D-aspartate receptor (NMDAR)-Calmodulin activation; synthesis of GABA via cell cycle regulators protein kinase B, glycogen synthase kinase and β-catenin; transportation of glutamate and GABA. Steady state stability, perturbation time-course simulation and sensitivity analysis were performed in COPASI after assigning the kinetic functions, optimizing the unknown parameters using random search and genetic algorithm. Results Study observations suggest that increased glutamate in hippocampus, similar to that seen in schizophrenia, could potentially be contributed by indirect pathway originated from BDNF. Deficient BDNF could suppress Glutamate decarboxylase 67-mediated GABA synthesis. Further, deficient BDNF corresponded to impaired transport via vesicular glutamate transporter, thereby further increasing the intracellular glutamate in GABAergic and glutamatergic cells. BDNF also altered calcium dependent neuroplasticity via NMDAR modulation. Sensitivity analysis showed that Calmodulin, cAMP response element-binding protein (CREB) and CREB regulated transcription coactivator-1 played significant role in this network. Conclusion The study presents in silico quantitative model of biochemical network constituting the key signaling molecules implicated in schizophrenia pathogenesis. It provides mechanistic insights into putative contribution of deficient BNDF towards alterations in neurotransmitters and neuroplasticity that are consistent with current understanding of the disorder. PMID:28449558

The use of transcranial magnetic stimulation to evaluate cortical excitability of lower limb musculature: Challenges and opportunities.

PubMed

Kesar, Trisha M; Stinear, James W; Wolf, Steven L

2018-05-05

Neuroplasticity is a fundamental yet relatively unexplored process that can impact rehabilitation of lower extremity (LE) movements. Transcranial magnetic stimulation (TMS) has gained widespread application as a non-invasive brain stimulation technique for evaluating neuroplasticity of the corticospinal pathway. However, a majority of TMS studies have been performed on hand muscles, with a paucity of TMS investigations focused on LE muscles. This perspective review paper proposes that there are unique methodological challenges associated with using TMS to evaluate corticospinal excitability of lower limb muscles. The challenges include: (1) the deeper location of the LE motor homunculus; (2) difficulty with targeting individual LE muscles during TMS; and (3) differences in corticospinal circuity controlling upper and lower limb muscles. We encourage future investigations that modify traditional methodological approaches to help address these challenges. Systematic TMS investigations are needed to determine the extent of overlap in corticomotor maps for different LE muscles. A simple, yet informative methodological solution involves simultaneous recordings from multiple LE muscles, which will provide the added benefit of observing how other relevant muscles co-vary in their responses during targeted TMS assessment directed toward a specific muscle. Furthermore, conventionally used TMS methods (e.g., determination of hot spot location and motor threshold) may need to be modified for TMS studies involving LE muscles. Additional investigations are necessary to determine the influence of testing posture as well as activation state of adjacent and distant LE muscles on TMS-elicited responses. An understanding of these challenges and solutions specific to LE TMS will improve the ability of neurorehabilitation clinicians to interpret TMS literature, and forge novel future directions for neuroscience research focused on elucidating neuroplasticity processes underlying locomotion and gait training.

The Effects of Stroke Type, Locus, and Extent on Long-Term Outcome of Gait Rehabilitation: The LEAPS Experience.

PubMed

Nadeau, Stephen E; Dobkin, Bruce; Wu, Samuel S; Pei, Qinglin; Duncan, Pamela W

2016-08-01

Background Paresis in stroke is largely a result of damage to descending corticospinal and corticobulbar pathways. Recovery of paresis predominantly reflects the impact on the neural consequences of this white matter lesion by reactive neuroplasticity (mechanisms involved in spontaneous recovery) and experience-dependent neuroplasticity, driven by therapy and daily experience. However, both theoretical considerations and empirical data suggest that type of stroke (large vessel distribution/lacunar infarction, hemorrhage), locus and extent of infarction (basal ganglia, right-hemisphere cerebral cortex), and the presence of leukoaraiosis or prior stroke might influence long-term recovery of walking ability. In this secondary analysis based on the 408 participants in the Locomotor Experience Applied Post-Stroke (LEAPS) study database, we seek to address these possibilities. Methods Lesion type, locus, and extent were characterized by the 2 neurologists in the LEAPS trial on the basis of clinical computed tomography and magnetic resonance imaging scans. A series of regression models was used to test our hypotheses regarding the effects of lesion type, locus, extent, and laterality on 2- to 12-month change in gait speed, controlling for baseline gait speed, age, and Berg Balance Scale score. Results Gait speed change at 1 year was significantly reduced in participants with basal ganglia involvement and prior stroke. There was a trend toward reduction of gait speed change in participants with lacunar infarctions. The presence of right-hemisphere cortical involvement had no significant impact on outcome. Conclusions Type, locus, and extent of lesion, and the loss of substrate for neuroplastic effect as a result of prior stroke may affect long-term outcome of rehabilitation of hemiparetic gait. © The Author(s) 2015.

Addressing Neuroplastic Changes in Distributed Areas of the Nervous System Associated With Chronic Musculoskeletal Disorders.

PubMed

Pelletier, René; Higgins, Johanne; Bourbonnais, Daniel

2015-11-01

Present interventions utilized in musculoskeletal rehabilitation are guided, in large part, by a biomedical model where peripheral structural injury is believed to be the sole driver of the disorder. There are, however, neurophysiological changes across different areas of the peripheral and central nervous systems, including peripheral receptors, dorsal horn of the spinal cord, brain stem, sensorimotor cortical areas, and the mesolimbic and prefrontal areas associated with chronic musculoskeletal disorders, including chronic low back pain, osteoarthritis, and tendon injuries. These neurophysiological changes appear not only to be a consequence of peripheral structural injury but also to play a part in the pathophysiology of chronic musculoskeletal disorders. Neurophysiological changes are consistent with a biopsychosocial formulation reflecting the underlying mechanisms associated with sensory and motor findings, psychological traits, and perceptual changes associated with chronic musculoskeletal conditions. These changes, therefore, have important implications in the clinical manifestation, pathophysiology, and treatment of chronic musculoskeletal disorders. Musculoskeletal rehabilitation professionals have at their disposal tools to address these neuroplastic changes, including top-down cognitive-based interventions (eg, education, cognitive-behavioral therapy, mindfulness meditation, motor imagery) and bottom-up physical interventions (eg, motor learning, peripheral sensory stimulation, manual therapy) that induce neuroplastic changes across distributed areas of the nervous system and affect outcomes in patients with chronic musculoskeletal disorders. Furthermore, novel approaches such as the use of transcranial direct current stimulation and repetitive transcranial magnetic stimulation may be utilized to help renormalize neurological function. Comprehensive treatment addressing peripheral structural injury as well as neurophysiological changes occurring across distributed areas of the nervous system may help to improve outcomes in patients with chronic musculoskeletal disorders. © 2015 American Physical Therapy Association.

miR-132 Regulates Dendritic Spine Structure by Direct Targeting of Matrix Metalloproteinase 9 mRNA.

PubMed

Jasińska, Magdalena; Miłek, Jacek; Cymerman, Iwona A; Łęski, Szymon; Kaczmarek, Leszek; Dziembowska, Magdalena

2016-09-01

Mir-132 is a neuronal activity-regulated microRNA that controls the morphology of dendritic spines and neuronal transmission. Similar activities have recently been attributed to matrix metalloproteinase-9 (MMP-9), an extrasynaptic protease. In the present study, we provide evidence that miR-132 directly regulates MMP-9 mRNA in neurons to modulate synaptic plasticity. With the use of luciferase reporter system, we show that miR-132 binds to the 3'UTR of MMP-9 mRNA to regulate its expression in neurons. The overexpression of miR-132 in neurons reduces the level of endogenous MMP-9 protein secretion. In synaptoneurosomes, metabotropic glutamate receptor (mGluR)-induced signaling stimulates the dissociation of miR-132 from polyribosomal fractions and shifts it towards the messenger ribonucleoprotein (mRNP)-containing fraction. Furthermore, we demonstrate that the overexpression of miR-132 in the cultured hippocampal neurons from Fmr1 KO mice that have increased synaptic MMP-9 level provokes enlargement of the dendritic spine heads, a process previously implicated in enhanced synaptic plasticity. We propose that activity-dependent miR-132 regulates structural plasticity of dendritic spines through matrix metalloproteinase 9.

The effects of blueberries on cognition and neuroplasticity

USDA-ARS?s Scientific Manuscript database

It has been demonstrated that consuming blueberries can prevent and even reverse the occurrence of neurochemical and behavioral changes associated with aging. Recent research suggests that consuming a high-fat diet (HFD) may result in behavioral deficits similar to those observed in aging animals. T...

Epigenetic Priming of Memory Updating during Reconsolidation to Attenuate Remote Fear Memories

PubMed Central

Gräff, Johannes; Joseph, Nadine F.; Horn, Meryl E.; Samiei, Alireza; Meng, Jia; Seo, Jinsoo; Rei, Damien; Bero, Adam W.; Phan, Trongha X.; Wagner, Florence; Holson, Edward; Xu, Jinbin; Sun, Jianjun; Neve, Rachael L.; Mach, Robert H.; Haggarty, Stephen J.; Tsai, Li-Huei

2014-01-01

Summary Traumatic events generate some of the most enduring forms of memories. Despite the elevated lifetime prevalence of anxiety disorders, effective strategies to attenuate long-term traumatic memories are scarce. The most efficacious treatments to diminish recent (i.e., day-old) traumata capitalize on memory updating mechanisms during reconsolidation that are initiated upon memory recall. Here, we show that, in mice, successful reconsolidation-updating paradigms for recent memories fail to attenuate remote (i.e., month-old) ones. We find that, whereas recent memory recall induces a limited period of hippocampal neuroplasticity mediated, in part, by S-nitrosylation of HDAC2 and histone acetylation, such plasticity is absent for remote memories. However, by using an HDAC2-targeting inhibitor (HDACi) during reconsolidation, even remote memories can be persistently attenuated. This intervention epigenetically primes the expression of neuroplasticity-related genes, which is accompanied by higher metabolic, synaptic, and structural plasticity. Thus, applying HDACis during memory reconsolidation might constitute a treatment option for remote traumata. PMID:24439381

Cortical Development and Neuroplasticity in Auditory Neuropathy Spectrum Disorder

PubMed Central

Sharma, Anu; Cardon, Garrett

2015-01-01

Cortical development is dependent to a large extent on stimulus-driven input. Auditory Neuropathy Spectrum Disorder (ANSD) is a recently described form of hearing impairment where neural dys-synchrony is the predominant characteristic. Children with ANSD provide a unique platform to examine the effects of asynchronous and degraded afferent stimulation on cortical auditory neuroplasticity and behavioral processing of sound. In this review, we describe patterns of auditory cortical maturation in children with ANSD. The disruption of cortical maturation that leads to these various patterns includes high levels of intra-individual cortical variability and deficits in cortical phase synchronization of oscillatory neural responses. These neurodevelopmental changes, which are constrained by sensitive periods for central auditory maturation, are correlated with behavioral outcomes for children with ANSD. Overall, we hypothesize that patterns of cortical development in children with ANSD appear to be markers of the severity of the underlying neural dys-synchrony, providing prognostic indicators of success of clinical intervention with amplification and/or electrical stimulation. PMID:26070426

Perinatal exposure to music protects spatial memory against callosal lesions.

PubMed

Amagdei, Anca; Balteş, Felicia Rodica; Avram, Julia; Miu, Andrei C

2010-02-01

Several studies have indicated that the exposure of rodents to music modulates brain development and neuroplasticity, by mechanisms that involve facilitated hippocampal neurogenesis, neurotrophin synthesis and glutamatergic signaling. This study focused on the potential protection that the perinatal exposure to music, between postnatal days 2 and 32, could offer against functional deficits induced by neonatal callosotomy in rats. The spontaneous alternation and marble-burying behaviors were longitudinally measured in callosotomized and control rats that had been exposed to music or not. The results indicated that the neonatal callosotomy-induced spontaneous alternation deficits that became apparent only after postnatal day 45, about the time when the rat corpus callosum reaches its maximal levels of myelination. The perinatal exposure to music efficiently protected the spontaneous alternation performance against the deficits induced by callosotomy. The present findings may offer important insights into music-induced neuroplasticity, relevant to brain development and neurorehabilitation. Copyright 2009 ISDN. Published by Elsevier Ltd. All rights reserved.

Amniotic fluid MMP-9 and neurotrophins in autism spectrum disorders: an exploratory study.

PubMed

Abdallah, Morsi W; Pearce, Brad D; Larsen, Nanna; Greaves-Lord, Kirstin; Nørgaard-Pedersen, Bent; Hougaard, David M; Mortensen, Erik L; Grove, Jakob

2012-12-01

Evidence suggests that some developmental disorders, such as autism spectrum disorders (ASDs), are caused by errors in brain plasticity. Given the important role of matrix metalloproteinases (MMPs) and neurotrophins (NTs) in neuroplasticity, amniotic fluid samples for 331 ASD cases and 698 frequency-matched controls were analyzed for levels of MMP-9, brain-derived neurotrophic factor, NT-4 and transforming growth factor-β utilizing a Danish historic birth cohort and Danish nationwide health registers. Laboratory measurements were performed using an in-house multiplex sandwich immunoassay Luminex xMAP method, and measurements were analyzed using tobit and logistic regression. Results showed elevated levels of MMP-9 in ASD cases compared with controls (crude and adjusted tobit regression P-values: 0.01 and 0.06). Our results highlight the importance of exploring the biologic impact of MMP-9 and potential therapeutic roles of its inhibitors in ASD and may indicate that neuroplastic impairments in ASD may present during pregnancy. © 2012 International Society for Autism Research, Wiley Periodicals, Inc.

Neuroplastic Sensorimotor Resting State Network Reorganization in Children With Hemiplegic Cerebral Palsy Treated With Constraint-Induced Movement Therapy.

PubMed

Manning, Kathryn Y; Menon, Ravi S; Gorter, Jan Willem; Mesterman, Ronit; Campbell, Craig; Switzer, Lauren; Fehlings, Darcy

2016-02-01

Using resting state functional magnetic resonance imaging (MRI), we aim to understand the neurologic basis of improved function in children with hemiplegic cerebral palsy treated with constraint-induced movement therapy. Eleven children including 4 untreated comparison subjects diagnosed with hemiplegic cerebral palsy were recruited from 3 clinical centers. MRI and clinical data were gathered at baseline and 1 month for both groups, and 6 months later for the case group only. After constraint therapy, the sensorimotor resting state network became more bilateral, with balanced contributions from each hemisphere, which was sustained 6 months later. Sensorimotor resting state network reorganization after therapy was correlated with a change in the Quality of Upper Extremity Skills Test score at 1 month (r = 0.79, P = .06), and Canadian Occupational Performance Measure scores at 6 months (r = 0.82, P = .05). This clinically correlated resting state network reorganization provides further evidence of the neuroplastic mechanisms underlying constraint-induced movement therapy. © The Author(s) 2015.

Harnessing Neuroplasticity to Promote Rehabilitation: CI Therapy for TBI

DTIC Science & Technology

2015-10-01

Efficacy, and Pharmacokinetics of SAGE- 547 Injection as Adjunctive Therapy for the Treatment of Super-Refractory Status Epilepticus (Szaflarski, PI...objective is to evaluate the safety and tolerability of SAGE-547 Injection (SAGE-547) in subjects in super-refractory status epilepticus (SRSE) This is a

Epigenetic Mechanisms in Mood Disorders: Targeting Neuroplasticity

PubMed Central

Fass, Daniel M.; Schroeder, Frederick A.; Perlis, Roy H.; Haggarty, Stephen J.

2013-01-01

Developing novel therapeutics and diagnostic tools based upon an understanding of neuroplasticity is critical in order to improve the treatment and ultimately the prevention of a broad range of nervous system disorders. In the case of mood disorders, such as major depressive disorder and bipolar disorder, where diagnoses are based solely on nosology rather than pathophysiology, there exists a clear unmet medical need to advance our understanding of the underlying molecular mechanisms and to develop fundamentally new mechanism experimental medicines with improved efficacy. In this context, recent preclinical molecular, cellular, and behavioral findings have begun to reveal the importance of epigenetic mechanisms that alter chromatin structure and dynamically regulate patterns of gene expression that may play a critical role in the pathophysiology of mood disorders. Here, we will review recent advances involving the use of animal models in combination with genetic and pharmacological probes to dissect the underlying molecular mechanisms and neurobiological consequence of targeting this chromatin-mediated neuroplasticity. We discuss evidence for the direct and indirect effects of mood stabilizers, antidepressants, and antipsychotics, among their many other effects, on chromatin-modifying enzmyes and on the epigenetic state of defined genomic loci, in defined cell types and in specific regions of the brain. These data, as well as findings from patient-derived tissue, have also begun to reveal alterations of epigenetic mechanisms in the pathophysiology and treatment of mood disorders. We summarize growing evidence supporting the notion that selectively targeting chromatin-modifying complexes, including those containing histone deacetylases (HDACs), provides a means to reversibly alter the acetylation state of neuronal chromatin and benefically impact neuronal activity-regulated gene transcription and mood-related behaviors. Looking beyond current knowledge, we discuss how high-resolution, whole-genome methodologies, such as RNA-sequencing (RNA-Seq) for transcriptome analysis and chromatin immunoprecipitation-sequencng (ChIP-Seq) for analyzing genome-wide occupancy of chromatin-associated factors, are beginning to provide an unprecedented view of both specific genomic loci as well as global properties of chromatin in the nervous system. These methodologies when applied to the characterization of model systems, including those of patient-derived induced pluripotent (iPS) cell and induced neurons (iNs), will greatly shape our understanding of epigenetic mechanisms and the impact of genetic variation on the regulatory regions of the human genome that can affect neuroplasticty. Finally, we point out critical unanswered questions and areas where additional data are needed in order to better understand the potential to target mechanisms of chromatin-mediated neuroplasticity for novel treatments of mood and other psychiatric disorders. PMID:23376737

Two types of exercise-induced neuroplasticity in congenital hemiparesis: a transcranial magnetic stimulation, functional MRI, and magnetoencephalography study.

PubMed

Juenger, Hendrik; Kuhnke, Nicola; Braun, Christoph; Ummenhofer, Frank; Wilke, Marko; Walther, Michael; Koerte, Inga; Delvendahl, Igor; Jung, Nikolai H; Berweck, Steffen; Staudt, Martin; Mall, Volker

2013-10-01

Early unilateral brain lesions can lead to a persistence of ipsilateral corticospinal projections from the contralesional hemisphere, which can enable the contralesional hemisphere to exert motor control over the paretic hand. In contrast to the primary motor representation (M1), the primary somatosensory representation (S1) of the paretic hand always remains in the lesioned hemisphere. Here, we report on differences in exercise-induced neuroplasticity between individuals with such ipsilateral motor projections (ipsi) and individuals with early unilateral lesions but 'healthy' contralateral motor projections (contra). Sixteen children and young adults with congenital hemiparesis participated in the study (contralateral [Contra] group: n=7, four females, three males; age range 10-30y, median age 16y; ipsilateral [Ipsi] group: n=9, four females, five males; age range 11-31y, median age 12y; Manual Ability Classification System levels I to II in all individuals in both groups). The participants underwent a 12-day intervention of constraint-induced movement therapy (CIMT), consisting of individual training (2h/d) and group training (8h/d). Before and after CIMT, hand function was tested using the Wolf Motor Function Test (WMFT) and diverging neuroplastic effects were observed by transcranial magnetic stimulation (TMS), functional magnetic resonance imaging (fMRI), and magnetoencephalography (MEG). Statistical analysis of TMS data was performed using the non-parametric Wilcoxon signed-rank test for pair-wise comparison; for fMRI standard statistical parametric and non-parametric mapping (SPM5, SnPM3) procedures (first level/second level) were carried out. Statistical analyses of MEG data involved analyses of variance (ANOVA) and t-tests. While MEG demonstrated a significant increase in S1 activation in both groups (p=0.012), TMS showed a decrease in M1 excitability in the Ipsi group (p=0.036), but an increase in M1 excitability in the Contra group (p=0.043). Similarly, fMRI showed a decrease in M1 activation in the Ipsi group, but an increase in activation in the M1-S1 region in the Contra group (for both groups p<0.001 [SnPM3] within the search volume). Different patterns of sensorimotor (re)organization in individuals with early unilateral lesions show, on a cortical level, different patterns of exercise-induced neuroplasticity. The findings help to improve the understanding of the general principles of sensorimotor learning and will help to develop more specific therapies for different pathologies in congenital hemiparesis. © 2013 Mac Keith Press.

Sensitive Periods of Emotion Regulation: Influences of Parental Care on Frontoamygdala Circuitry and Plasticity

ERIC Educational Resources Information Center

Gee, Dylan G.

2016-01-01

Early caregiving experiences play a central role in shaping emotional development, stress physiology, and refinement of limbic circuitry. Converging evidence across species delineates a sensitive period of heightened neuroplasticity when frontoamygdala circuitry is especially amenable to caregiver inputs early in life. During this period, parental…

Translational Research in Aphasia: From Neuroscience to Neurorehabilitation

ERIC Educational Resources Information Center

Raymer, Anastasia M.; Beeson, Pelagie; Holland, Audrey; Kendall, Diane; Maher, Lynn M.; Martin, Nadine; Murray, Laura; Rose, Miranda; Thompson, Cynthia K.; Turkstra, Lyn; Altmann, Lori; Boyle, Mary; Conway, Tim; Hula, William; Kearns, Kevin; Rapp, Brenda; Simmons-Mackie, Nina; Gonzalez Rothi, Leslie J.

2008-01-01

Purpose: In this article, the authors encapsulate discussions of the Language Work Group that took place as part of the Workshop in Plasticity/NeuroRehabilitation Research at the University of Florida in April 2005. Method: In this narrative review, they define neuroplasticity and review studies that demonstrate neural changes associated with…

Reduced Sleep Spindle Activity in Early-Onset and Elevated Risk for Depression

ERIC Educational Resources Information Center

Lopez, Jorge; Hoffmann, Robert; Armitage, Roseanne

2010-01-01

Objective: Sleep disturbances are common in major depressive disorder (MDD), although polysomnographic (PSG) abnormalities are more prevalent in adults than in children and adolescents with MDD. Sleep spindle activity (SPA) is associated with neuroplasticity mechanisms during brain maturation and is more abundant in childhood and adolescence than…

Mild Thyroid Hormone Insufficiency During Development Compromises Activity-Dependent Neuroplasticity in the Hippocampus of Adult Make Rats

EPA Science Inventory

Severe thyroid hormone (TH) deficiency during critical phases of brain development results in irreversible neurological and cognitive impairments. The mechanisms accounting for this are likely multifactorial, and are not fully understood. Here we pursue the possibility that one i...

Genre, Identity, and the Brain: Insights from Neuropsychology

ERIC Educational Resources Information Center

Clark, Irene

2016-01-01

The article explores several perspectives on the interconnection between genre and identity, an issue that has generated significant scholarship in rhetorical genre studies. It suggests that current work in neuroplasticity--that is, changes in the brain that can occur through learning and experience--complicates and problematizes the issue and is…

Default-Mode Network Functional Connectivity in Aphasia: Therapy-Induced Neuroplasticity

ERIC Educational Resources Information Center

Marcotte, Karine; Perlbarg, Vincent; Marrelec, Guillaume; Benali, Habib; Ansaldo, Ana Ines

2013-01-01

Previous research on participants with aphasia has mainly been based on standard functional neuroimaging analysis. Recent studies have shown that functional connectivity analysis can detect compensatory activity, not revealed by standard analysis. Little is known, however, about the default-mode network in aphasia. In the current study, we studied…

Family-Based Training Program Improves Brain Function, Cognition, and Behavior in Lower Socioeconomic Status Preschoolers

ERIC Educational Resources Information Center

Pakulak, Eric; Stevens, Courtney; Bell, Theodore A.; Fanning, Jessica; Klein, Scott; Isbell, Elif; Neville, Helen

2013-01-01

Over the course of several years of research, the authors have employed psychophysics, electrophysiological (ERP) and magnetic resonance imaging (MRI) techniques to study the development and neuroplasticity of the human brain. During this time, they observed that different brain systems and related functions display markedly different degrees or…

Mechanisms of Aphasia Recovery after Stroke and the Role of Noninvasive Brain Stimulation

ERIC Educational Resources Information Center

Hamilton, Roy H.; Chrysikou, Evangelia G.; Coslett, Branch

2011-01-01

One of the most frequent symptoms of unilateral stroke is aphasia, the impairment or loss of language functions. Over the past few years, behavioral and neuroimaging studies have shown that rehabilitation interventions can promote neuroplastic changes in aphasic patients that may be associated with the improvement of language functions. Following…

Role of the Ventral Tegmental Area in Methamphetamine Extinction: AMPA Receptor-Mediated Neuroplasticity

ERIC Educational Resources Information Center

Chen Han-Ting; Chen, Jin-Chung

2015-01-01

The molecular mechanisms underlying drug extinction remain largely unknown, although a role for medial prefrontal cortex (mPFC) glutamate neurons has been suggested. Considering that the mPFC sends glutamate efferents to the ventral tegmental area (VTA), we tested whether the VTA is involved in methamphetamine (METH) extinction via conditioned…

Biologic and plastic effects of experimental traumatic brain injury treatment paradigms and their relevance to clinical rehabilitation

PubMed Central

Garcia, Alexandra N.; Shah, Mansi A.; Dixon, C. Edward; Wagner, Amy K.; Kline, Anthony E.

2011-01-01

Neuroplastic changes, whether induced by traumatic brain injury (TBI) or therapeutic interventions, alter neurobehavioral outcome. Here we present several treatment strategies that have been evaluated using experimental TBI models and discuss potential mechanisms of action (i.e., plasticity) and how such changes affect function. PMID:21703575

76 FR 50486 - Center for Scientific Review Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-15

... Review. Date: September 15-16, 2011. Time: 9 a.m. to 5 p.m. Agenda: To review and evaluate grant...; Clinical Neuroplasticity and Neurotransmitters Study Section. Date: September 19-20, 2011. Time: 8 a.m. to 5 p.m. Agenda: To review and evaluate grant applications. Place: The Westin Seattle, 1900 Fifth...

76 FR 61721 - Eunice Kennedy Shriver National Institute of Child Health & Human Development; Notice of Closed...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-05

... National Institute of Child Health & Human Development; Notice of Closed Meeting Pursuant to section 10(d... Institute of Child Health and Human Development, Special Emphasis Panel, Neuroplasticity and the Maternal... Scientific Review, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, 6100...

Blueberry supplementation attenuates microglia activation and increases neuroplasticity in mice consuming a high fat diet

USDA-ARS?s Scientific Manuscript database

Objectives: Consuming a high-fat diet (HFD) may result in behavioral deficits similar to those observed in aging animals. Blueberries may prevent and even reverse age-related alterations in neurochemistry and behavior. It was previously demonstrated that middle-aged mice fed HFD had impaired memory;...

A Natural Teaching Method Based on Learning Theory.

ERIC Educational Resources Information Center

Smilkstein, Rita

1991-01-01

The natural teaching method is active and student-centered, based on schema and constructivist theories, and informed by research in neuroplasticity. A schema is a mental picture or understanding of something we have learned. Humans can have knowledge only to the degree to which they have constructed schemas from learning experiences and practice.…

Neurodiversity: The Future of Special Education?

ERIC Educational Resources Information Center

Armstrong, Thomas

2017-01-01

The way special education is carried out in U.S. schools must change. Special education has become weighed down by its emphasis on deficits and disorders: As regular education has opened to new ways of thinking about brain neuroplasticity, growth mindsets, and other innovations, special education has held fast to its diagnostic categories,…

Participation of group I p21-activated kinases in neuroplasticity.

PubMed

Koth, André P; Oliveira, Bruno R; Parfitt, Gustavo M; Buonocore, Juliana de Quadros; Barros, Daniela M

2014-01-01

PAKs are a family of serine/threonine protein kinases activated by small GTPases of the Rho family, including Rac and Cdc42, and are categorized into group I (isoforms 1, 2 and 3) and group II (isoforms 4, 5 and 6). PAK1 and PAK3 are critically involved in biological mechanisms associated with neurodevelopment, neuroplasticity and maturation of the nervous system, and changes in their activity have been detected in pathological disorders, such as Alzheimer's disease, Huntington's disease and mental retardation. The group I PAKs have been associated with neurological processes due to their involvement in intracellular mechanisms that result in molecular and cellular morphological alterations that promote cytoskeletal outgrowth, increasing the efficiency of synaptic transmission. Their substrates in these processes include other intracellular signaling molecules, such as Raf, Mek and LIMK, as well as other components of the cytoskeleton, such as MLC and FLNa. In this review, we describe the characteristics of group I PAKs, such as their molecular structure, mechanisms of activation and importance in the neurobiological processes involved in synaptic plasticity. Copyright © 2014 Elsevier Ltd. All rights reserved.

'Who is the ideal candidate?': decisions and issues relating to visual neuroprosthesis development, patient testing and neuroplasticity

NASA Astrophysics Data System (ADS)

Merabet, Lotfi B.; Rizzo, Joseph F., III; Pascual-Leone, Alvaro; Fernandez, Eduardo

2007-03-01

Appropriate delivery of electrical stimulation to intact visual structures can evoke patterned sensations of light in individuals who have been blind for many years. This pivotal finding has lent credibility to the concept of restoring functional vision by artificial means. As numerous groups worldwide pursue human clinical testing with visual prosthetic devices, it is becoming increasingly clear that there remains a considerable gap between the challenges of prosthetic device development and the rehabilitative strategies needed to implement this new technology in patients. An important area of future work will be the development of appropriate pre- and post-implantation measures of performance and establishing candidate selection criteria in order to quantify technical advances, guide future device design and optimize therapeutic success. We propose that the selection of an 'ideal' candidate should also be considered within the context of the variable neuroplastic changes that follow vision loss. Specifically, an understanding of the adaptive and compensatory changes that occur within the brain could assist in guiding the development of post-implantation rehabilitative strategies and optimize behavioral outcomes.

Cerebral versus Ocular Visual Impairment: The Impact on Developmental Neuroplasticity.

PubMed

Martín, Maria B C; Santos-Lozano, Alejandro; Martín-Hernández, Juan; López-Miguel, Alberto; Maldonado, Miguel; Baladrón, Carlos; Bauer, Corinna M; Merabet, Lotfi B

2016-01-01

Cortical/cerebral visual impairment (CVI) is clinically defined as significant visual dysfunction caused by injury to visual pathways and structures occurring during early perinatal development. Depending on the location and extent of damage, children with CVI often present with a myriad of visual deficits including decreased visual acuity and impaired visual field function. Most striking, however, are impairments in visual processing and attention which have a significant impact on learning, development, and independence. Within the educational arena, current evidence suggests that strategies designed for individuals with ocular visual impairment are not effective in the case of CVI. We propose that this variance may be related to differences in compensatory neuroplasticity related to the type of visual impairment, as well as underlying alterations in brain structural connectivity. We discuss the etiology and nature of visual impairments related to CVI, and how advanced neuroimaging techniques (i.e., diffusion-based imaging) may help uncover differences between ocular and cerebral causes of visual dysfunction. Revealing these differences may help in developing future strategies for the education and rehabilitation of individuals living with visual impairment.

Cerebral versus Ocular Visual Impairment: The Impact on Developmental Neuroplasticity

PubMed Central

Martín, Maria B. C.; Santos-Lozano, Alejandro; Martín-Hernández, Juan; López-Miguel, Alberto; Maldonado, Miguel; Baladrón, Carlos; Bauer, Corinna M.; Merabet, Lotfi B.

2016-01-01

Cortical/cerebral visual impairment (CVI) is clinically defined as significant visual dysfunction caused by injury to visual pathways and structures occurring during early perinatal development. Depending on the location and extent of damage, children with CVI often present with a myriad of visual deficits including decreased visual acuity and impaired visual field function. Most striking, however, are impairments in visual processing and attention which have a significant impact on learning, development, and independence. Within the educational arena, current evidence suggests that strategies designed for individuals with ocular visual impairment are not effective in the case of CVI. We propose that this variance may be related to differences in compensatory neuroplasticity related to the type of visual impairment, as well as underlying alterations in brain structural connectivity. We discuss the etiology and nature of visual impairments related to CVI, and how advanced neuroimaging techniques (i.e., diffusion-based imaging) may help uncover differences between ocular and cerebral causes of visual dysfunction. Revealing these differences may help in developing future strategies for the education and rehabilitation of individuals living with visual impairment. PMID:28082927

Improving Emotional Intelligence through Personality Development: The Effect of the Smart Phone Application based Dharma Life Program on Emotional Intelligence

PubMed Central

Poonamallee, Latha; Harrington, Alex M.; Nagpal, Manisha; Musial, Alec

2018-01-01

Emotional intelligence is established to predict success in leadership effectiveness in various contexts and has been linked to personality factors. This paper introduces Dharma Life Program, a novel approach to improving emotional intelligence by targeting maladaptive personality traits and triggering neuroplasticity through the use of a smart-phone application and mentoring. The program uses neuroplasticity to enable users to create a more adaptive application of their maladaptive traits, thus improving their emotional intelligence. In this study 26 participants underwent the Dharma Life Program in a leadership development setting. We assessed their emotional and social intelligence before and after the Dharma Life Program intervention using the Emotional and Social Competency Inventory (ESCI). The study found a significant improvement in the lowest three competencies and a significant improvement in almost all domains for the entire sample. Our findings suggest that the completion of the Dharma Life Program has a significant positive effect on Emotional and Social Competency scores and offers a new avenue for improving emotional intelligence competencies. PMID:29527182

Improving Emotional Intelligence through Personality Development: The Effect of the Smart Phone Application based Dharma Life Program on Emotional Intelligence.

PubMed

Poonamallee, Latha; Harrington, Alex M; Nagpal, Manisha; Musial, Alec

2018-01-01

Emotional intelligence is established to predict success in leadership effectiveness in various contexts and has been linked to personality factors. This paper introduces Dharma Life Program, a novel approach to improving emotional intelligence by targeting maladaptive personality traits and triggering neuroplasticity through the use of a smart-phone application and mentoring. The program uses neuroplasticity to enable users to create a more adaptive application of their maladaptive traits, thus improving their emotional intelligence. In this study 26 participants underwent the Dharma Life Program in a leadership development setting. We assessed their emotional and social intelligence before and after the Dharma Life Program intervention using the Emotional and Social Competency Inventory (ESCI). The study found a significant improvement in the lowest three competencies and a significant improvement in almost all domains for the entire sample. Our findings suggest that the completion of the Dharma Life Program has a significant positive effect on Emotional and Social Competency scores and offers a new avenue for improving emotional intelligence competencies.

Cross-activation and Detraining Effects of Tongue Exercise in Aged Rats

PubMed Central

Schaser, Allison J.; Ciucci, Michelle R.; Connor, Nadine P.

2015-01-01

Voice and swallowing deficits can occur with aging. Tongue exercise paired with a swallow may be used to treat swallowing disorders, but may also benefit vocal function due to cross-system activation effects. It is unknown how exercise-based neuroplasticity contributes to behavior and maintenance following treatment. Eighty rats were used to examine behavioral parameters and changes in neurotrophins after tongue exercise paired with a swallow. Tongue forces and ultrasonic vocalizations were recorded before and after training/detraining in young and old rats. Tissue was analyzed for neurotrophin content. Results showed tongue exercise paired with a swallow was associated with increased tongue forces at all ages. Gains diminished after detraining in old rats. Age-related changes in vocalizations, neurotrophin 4 (NT4), and brain derived neurotrophic factor (BDNF) were found. Minimal cross-system activation effects were observed. Neuroplastic benefits were demonstrated with exercise in old rats through behavioral improvements and up-regulation of BDNF in the hypoglossal nucleus. Tongue exercise paired with a swallow should be developed, studied, and optimized in human clinical research to treat swallowing and voice disorders in elderly people. PMID:26477376

Cross-education of strength and skill: an old idea with applications in the aging nervous system.

PubMed

Barss, Trevor S; Pearcey, Gregory E P; Zehr, E Paul

2016-03-01

Edward Wheeler Scripture's 1894 work out of the Yale Psychological Laboratory has been influential in identifying the nervous system's contribution to the bilateral improvements that are seen with unilateral strength and skill training. Scripture coined the term "cross-education" to describe this improvement in the untrained contralateral limb. While physiological changes accompany aging that may negatively affect the performance of physical tasks, far too much credit has been given to the natural aging process rather than the effects of inactivity. Emerging evidence indicates strength or skill training interventions induce significant neuroplasticity in an aging population. The model of unilateral training provides a unique approach in which to elicit such plasticity. This brief review highlights the innate ability of the nervous system to adapt to unilateral strength and skill training interventions, regardless of age, and provides a novel perspective on the robust plastic ability of the aging nervous system.

Blind Braille readers mislocate tactile stimuli.

PubMed

Sterr, Annette; Green, Lisa; Elbert, Thomas

2003-05-01

In a previous experiment, we observed that blind Braille readers produce errors when asked to identify on which finger of one hand a light tactile stimulus had occurred. With the present study, we aimed to specify the characteristics of this perceptual error in blind and sighted participants. The experiment confirmed that blind Braille readers mislocalised tactile stimuli more often than sighted controls, and that the localisation errors occurred significantly more often at the right reading hand than at the non-reading hand. Most importantly, we discovered that the reading fingers showed the smallest error frequency, but the highest rate of stimulus attribution. The dissociation of perceiving and locating tactile stimuli in the blind suggests altered tactile information processing. Neuroplasticity, changes in tactile attention mechanisms as well as the idea that blind persons may employ different strategies for tactile exploration and object localisation are discussed as possible explanations for the results obtained.

Meta-analysis of six genes (BDNF, DRD1, DRD3, DRD4, GRIN2B and MAOA) involved in neuroplasticity and the risk for alcohol dependence.

PubMed

Forero, Diego A; López-León, Sandra; Shin, Hyoung Doo; Park, Byung Lae; Kim, Dai-Jin

2015-04-01

Alcohol-related problems have a large impact on human health, accounting for around 4% of deaths and 4.5% of disability-adjusted life-years around the world. Genetic factors could explain a significant fraction of the risk for alcohol dependence (AD). Recent meta-analyses have found significant pooled odds ratios (ORs) for variants in the ADH1B, ADH1C, DRD2 and HTR2A genes. In the present study, we carried out a meta-analysis of common variants in 6 candidate genes involved in neurotransmission and neuroplasticity: BDNF, DRD1, DRD3, DRD4, GRIN2B and MAOA. We carried out a systematic search for published association studies that analyzed the genes of interest. Relevant articles were retrieved and demographic and genetic data were extracted. Pooled ORs were calculated using a random-effects model using the Meta-Analyst program. Dominant, recessive and allelic models were tested and analyses were also stratified by ethnicity. Forty two published studies were included in the current meta-analysis: BDNF-rs6265 (nine studies), DRD1-rs4532 (four studies), DRD3-rs6280 (eleven studies), DRD4-VNTR (seven studies), GRIN2B-rs1806201 (three studies) and MAOA-uVNTR (eight studies). We did not find significant pooled ORs for any of the six genes, under different models and stratifying for ethnicity. In terms of the number of candidate genes included, this is one of the most comprehensive meta-analyses for genetics of AD. Pooled ORs did not support consistent associations with any of the six candidate genes tested. Future studies of novel genes of functional relevance and meta-analyses of quantitative endophenotypes could identify further susceptibility molecular factors for AD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Long-term neuroplasticity of the face primary motor cortex and adjacent somatosensory cortex induced by tooth loss can be reversed following dental implant replacement in rats.

PubMed

Avivi-Arber, Limor; Lee, Jye-Chang; Sood, Mandeep; Lakschevitz, Flavia; Fung, Michelle; Barashi-Gozal, Maayan; Glogauer, Michael; Sessle, Barry J

2015-11-01

Tooth loss is common, and exploring the neuroplastic capacity of the face primary motor cortex (face-M1) and adjacent primary somatosensory cortex (face-S1) is crucial for understanding how subjects adapt to tooth loss and their prosthetic replacement. The aim was to test if functional reorganization of jaw and tongue motor representations in the rat face-M1 and face-S1 occurs following tooth extraction, and if subsequent dental implant placement can reverse this neuroplasticity. Rats (n = 22) had the right maxillary molar teeth extracted under local and general anesthesia. One month later, seven rats had dental implant placement into healed extraction sites. Naive rats (n = 8) received no surgical treatment. Intracortical microstimulation (ICMS) and recording of evoked jaw and tongue electromyographic responses were used to define jaw and tongue motor representations at 1 month (n = 8) or 2 months (n = 7) postextraction, 1 month postimplant placement, and at 1-2 months in naive rats. There were no significant differences across study groups in the onset latencies of the ICMS-evoked responses (P > 0.05), but in comparison with naive rats, tooth extraction caused a significant (P < 0.05) and sustained (1-2 months) decreased number of ICMS-defined jaw and tongue sites within face-M1 and -S1, and increased thresholds of ICMS-evoked responses in these sites. Furthermore, dental implant placement reversed the extraction-induced changes in face-S1, and in face-M1 the number of jaw sites even increased as compared to naive rats. These novel findings suggest that face-M1 and adjacent face-S1 may play a role in adaptive mechanisms related to tooth loss and their replacement with dental implants. © 2015 Wiley Periodicals, Inc.

Insights into Rapid Modulation of Neuroplasticity by Brain Estrogens

PubMed Central

Woolfrey, Kevin M.; Penzes, Peter

2013-01-01

Converging evidence from cellular, electrophysiological, anatomic, and behavioral studies suggests that the remodeling of synapse structure and function is a critical component of cognition. This modulation of neuroplasticity can be achieved through the actions of numerous extracellular signals. Moreover, it is thought that it is the integration of different extracellular signals regulation of neuroplasticity that greatly influences cognitive function. One group of signals that exerts powerful effects on multiple neurologic processes is estrogens. Classically, estrogens have been described to exert their effects over a period of hours to days. However, there is now increasing evidence that estrogens can rapidly influence multiple behaviors, including those that require forebrain neural circuitry. Moreover, these effects are found in both sexes. Critically, it is now emerging that the modulation of cognition by rapid estrogenic signaling is achieved by activation of specific signaling cascades and regulation of synapse structure and function, cumulating in the rewiring of neural circuits. The importance of understanding the rapid effects of estrogens on forebrain function and circuitry is further emphasized as investigations continue to consider the potential of estrogenic-based therapies for neuropathologies. This review focuses on how estrogens can rapidly influence cognition and the emerging mechanisms that underlie these effects. We discuss the potential sources and the biosynthesis of estrogens within the brain and the consequences of rapid estrogenic-signaling on the remodeling of neural circuits. Furthermore, we argue that estrogens act via distinct signaling pathways to modulate synapse structure and function in a manner that may vary with cell type, developmental stage, and sex. Finally, we present a model in which the coordination of rapid estrogenic-signaling and activity-dependent stimuli can result in long-lasting changes in neural circuits, contributing to cognition, with potential relevance for the development of novel estrogenic-based therapies for neurodevelopmental or neurodegenerative disorders. PMID:24076546

The absence of 5-HT4 receptors modulates depression- and anxiety-like responses and influences the response of fluoxetine in olfactory bulbectomised mice: Adaptive changes in hippocampal neuroplasticity markers and 5-HT1A autoreceptor.

PubMed

Amigó, J; Díaz, A; Pilar-Cuéllar, F; Vidal, R; Martín, A; Compan, V; Pazos, A; Castro, E

2016-12-01

Preclinical studies support a critical role of 5-HT 4 receptors (5-HT 4 Rs) in depression and anxiety, but their influence in depression- and anxiety-like behaviours and the effects of antidepressants remain partly unknown. We evaluated 5-HT 4 R knockout (KO) mice in different anxiety and depression paradigms and mRNA expression of some neuroplasticity markers (BDNF, trkB and Arc) and the functionality of 5-HT 1A R. Moreover, the implication of 5-HT 4 Rs in the behavioural and molecular effects of chronically administered fluoxetine was assessed in naïve and olfactory bulbectomized mice (OBX) of both genotypes. 5-HT 4 R KO mice displayed few specific behavioural impairments including reduced central activity in the open-field (anxiety), and decreased sucrose consumption and nesting behaviour (anhedonia). In these mice, we measured increased levels of BDNF and Arc mRNA and reduced levels of trkB mRNA in the hippocampus, and a desensitization of 5-HT 1A autoreceptors. Chronic administration of fluoxetine elicited similar behavioural effects in WT and 5-HT 4 R KO mice on anxiety-and depression-related tests. Following OBX, locomotor hyperactivity and anxiety were similar in both genotypes. Interestingly, chronic fluoxetine failed to reverse this OBX-induced syndrome in 5-HT 4 R KO mice, a response associated with differential effects in hippocampal neuroplasticity biomarkers. Fluoxetine reduced hippocampal Arc and BDNF mRNA expressions in WT but not 5-HT 4 R KO mice subjected to OBX. These results demonstrate that the absence of 5-HT 4 Rs triggers adaptive changes that could maintain emotional states, and that the behavioural and molecular effects of fluoxetine under pathological depression appear to be critically dependent on 5-HT 4 Rs. Copyright © 2016 Elsevier Ltd. All rights reserved.

The development of a sensory substitution system for the sexual rehabilitation of men with chronic spinal cord injury.

PubMed

Borisoff, Jaimie F; Elliott, Stacy L; Hocaloski, Shea; Birch, Gary E

2010-11-01

Sexual health is often severely impacted after spinal cord injury (SCI). Current research has primarily addressed male erection and fertility, when in fact pleasure and orgasm are top priorities for functional recovery. Sensory substitution technology operates by communicating input from a lost sensory pathway to another intact sensory modality. It was hypothesized that through training and neuroplasticity, mapped tongue sensations would be interpreted as sensory perceptions arising from insensate genitalia, and improve the sexual experience. To report the development of a sensory substitution system for the sexual rehabilitation of men with chronic SCI. Subjects performed sexual self-stimulation while using a novel sensory substitution device that mapped the stroking motion of the hand to a congruous flow of electrocutaneous sensations on the tongue. Three questionnaires, along with structured interviews, were used to rate the perceived sexual sensations following each training session. Subjects completed 20 sessions over approximately 8 weeks of training. Each subject reported an increased level of sexual pleasure soon after training with the device. Each subject also reported specific perceptions of cutaneous-like sensations below their lesion that matched their hand motion. Later sessions, while remaining pleasurable and interesting, were inconsistent, and no subject reported an orgasmic feeling during a session. The subjects were all interested in continuing training with the device at home, if possible, in the future. This study is the first to show that sensory substitution is a possible therapeutic avenue for sexual rehabilitation in people lacking normal genital sexual sensations. However more research, for instance on frequency and duration of training, is needed in order to induce functional lasting neuroplasticity. In the near term, SCI rehabilitation should more fully address sexuality and the role of neuroplasticity for promoting the maximal potential for sexual pleasure and orgasm. © 2010 International Society for Sexual Medicine.

Action of insecticidal N-alkylamides at site 2 of the voltage-sensitive sodium channel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ottea, J.A.; Payne, G.T.; Soderlund, D.M.

1990-08-01

Nine synthetic N-alkylamides were examined as inhibitors of the specific binding of ({sup 3}H)batrachotoxinin A 20{alpha}-benzoate (({sup 3}H)BTX-B) to sodium channels and as activators of sodium uptake in mouse brain synaptoneurosomes. In the presence of scorpion (Leiurus quinquestriatus) venom, the six insecticidal analogues were active as both inhibitors of ({sup 3}H)BTX-B binding and stimulators of sodium uptake. These findings are consistent with an action of these compounds at the alkaloid activator recognition site (site 2) of the voltage-sensitive sodium channel. The three noninsecticidal N-alkylamides also inhibited ({sup 3}H)BTX-B binding but were ineffective as activators of sodium uptake. Concentration-response studies revealedmore » that some of the insecticidal amides also enhanced sodium uptake through a second, high-affinity interaction that does not involve site 2, but this secondary effect does not appear to be correlated with insecticidal activity. The activities of N-alkylamides as sodium channel activators were influenced by the length of the alkenyl chain and the location of unsaturation within the molecule. These results further define the actions of N-alkylamides on sodium channels and illustrate the significance of the multiple binding domains of the sodium channel as target sites for insect control agents.« less

KB220Z™ a Pro-Dopamine Regulator Associated with the Protracted, Alleviation of Terrifying Lucid Dreams. Can We Infer Neuroplasticity-induced Changes in the Reward Circuit?

PubMed Central

McLaughlin, Thomas; Febo, Marcelo; Badgaiyan, Rajendra D.; Barh, Debmalya; Dushaj, Kristina; Braverman, Eric R.; Li, Mona; Madigan, Margaret A.; Blum, Kenneth

2017-01-01

Background Recent reports by our laboratory have indicated that lucid dreams may be linked to psychiatric conditions, including Attention Deficit Hyperactivity Disorder (ADHD) and other Reward Deficiency Syndrome-related diagnoses. In the latter case, it has been our observation that such lucid dreams can be unpleasant and frequently terrifying. Case presentations We present four cases of a dramatic and persistent alleviation of terrifying, lucid dreams in patients diagnosed with ADHD/PTSD and/or opiate/opioid addiction. The amelioration of such dreams could well be permanent, since the patients had stopped taking the nutraceutical for between 10 to 12 months, without their recollection or recurrence. In the first case, the patient is a 47-year-old, married male who required continued Buprenorphine/ Naloxone (Suboxone) treatment. The second case involved a 32-year-old female with the sole diagnosis of ADHD. The third case involves a 38-year-old male who carried the diagnoses of Substance Use Dependence and ADHD. The fourth case involved a 50-year-old female with the diagnoses of Alcohol Abuse, ADHD and Posttraumatic Stress Disorder. Results In order to attempt to understand the possibility of neuroplasticity, we evaluated the effect of KB220Z in non-opioid-addicted rats utilizing functional Magnetic Resonance Imaging methodology. While we cannot make a definitive claim because rat brain functional connectivity may not be exactly the same as humans, it does provide some interesting clues. We did find following seeding of the dorsal hippocampus, enhanced connectivity volume across several Regions of Interest (ROI), with the exception of the pre- frontal cortex. Interestingly, the latter region is only infrequently activated in lucid human dreaming, when the dreamer reports that he/she had the thought that they were dreaming during the lucid dream. Conclusions The four patients initially reported a gradual but, then, complete amelioration of their long-term, terrifying, lucid dreams, while taking KB220Z. The persistent amelioration of these dreams continued for up to 12 months, after a self-initiated, cessation of use of KB220Z. These particular cases raise the scientific possibility that KB200Z increases both dopamine stability as well as functional connectivity between networks of brain reward circuitry in both rodents and humans. The increase in connectivity volume in rodents suggest the induction of neuroplasticity changes, which may be analogous to those involved in human lucid dreaming as well as Rapid Eye Movement sleep. The possibility that the complex induces long-term, neuroplasticity changes must await more intensive investigations, involving large-population, double-blinded studies. PMID:28210713

Art Therapy: The Visual Spatial Factor and the Hippocampus. 2nd Revision

ERIC Educational Resources Information Center

Del Giacco, Maureen

2010-01-01

In this writing related to neuro-plasticity, we are shown that changes in the brain can occur with repeated use of sensory stimuli, with both visual and motor interventions. Keeping these important scientific contributions in mind, I will briefly summarize why the choice of the arts-based DAT method of psychotherapy over traditional verbally based…

Plasticity of reward neurocircuitry and the 'dark side' of drug addiction.

PubMed

Koob, George F; Le Moal, Michel

2005-11-01

Drug seeking is associated with activation of reward neural circuitry. Here we argue that drug addiction also involves a 'dark side'--a decrease in the function of normal reward-related neurocircuitry and persistent recruitment of anti-reward systems. Understanding the neuroplasticity of the dark side of this circuitry is the key to understanding vulnerability to addiction.

Associative Learning and Sensory Neuroplasticity: How Does It Happen and What Is It Good For?

ERIC Educational Resources Information Center

McGann, John P.

2015-01-01

Historically, the body's sensory systems have been presumed to provide the brain with raw information about the external environment, which the brain must interpret to select a behavioral response. Consequently, studies of the neurobiology of learning and memory have focused on circuitry that interfaces between sensory inputs and behavioral…

Memory Deficits Are Associated with Impaired Ability to Modulate Neuronal Excitability in Middle-Aged Mice

ERIC Educational Resources Information Center

Kaczorowski, Catherine C.; Disterhoft, John F.

2009-01-01

Normal aging disrupts hippocampal neuroplasticity and learning and memory. Aging deficits were exposed in a subset (30%) of middle-aged mice that performed below criterion on a hippocampal-dependent contextual fear conditioning task. Basal neuronal excitability was comparable in middle-aged and young mice, but learning-related modulation of the…

Connecting Neuroscientific Discoveries with the Value of a Higher Education Degree

ERIC Educational Resources Information Center

Bresciani, Marilee J.

2012-01-01

While there are hypotheses and theories about which portions of the brain appear to regulate which types of thinking and emotion, people aren't sure how to "change" those parts of the brain to improve critical thinking. Furthermore, while recent studies point to something called neuroplasticity, which hypothesizes that what one does, what one…

Exercise, Stress Resistance, and Central Serotonergic Systems

PubMed Central

Greenwood, Benjamin N.; Fleshner, Monika

2015-01-01

Voluntary exercise reduces the incidence of stress-related psychiatric disorders in humans and prevents serotonin-dependent behavioral consequences of stress in rodents. Evidence reviewed herein is consistent with the hypothesis that exercise increases stress resistance by producing neuroplasticity at multiple sites of the central serotonergic system, which all help to limit the behavioral impact of acute increases in serotonin during stressor exposure. PMID:21508844

Old Dogs Learning New Tricks: Neuroplasticity beyond the Juvenile Period

ERIC Educational Resources Information Center

Lillard, Angeline S.; Erisir, Alev

2011-01-01

Twenty years ago, the prevalent view in Psychology was that although learning and the formation of new memories are lifelong occurrences, the neural changes associated with these events were all in the existing receptors. No new neural hardware, from synapses to neurons, was thought to appear after a protracted period early in life. In the past 20…

Vertically aligned carbon nanofiber as nano-neuron interface for monitoring neural function.

PubMed

Yu, Zhe; McKnight, Timothy E; Ericson, M Nance; Melechko, Anatoli V; Simpson, Michael L; Morrison, Barclay

2012-05-01

Neural chips, which are capable of simultaneous multisite neural recording and stimulation, have been used to detect and modulate neural activity for almost thirty years. As neural interfaces, neural chips provide dynamic functional information for neural decoding and neural control. By improving sensitivity and spatial resolution, nano-scale electrodes may revolutionize neural detection and modulation at cellular and molecular levels as nano-neuron interfaces. We developed a carbon-nanofiber neural chip with lithographically defined arrays of vertically aligned carbon nanofiber electrodes and demonstrated its capability of both stimulating and monitoring electrophysiological signals from brain tissues in vitro and monitoring dynamic information of neuroplasticity. This novel nano-neuron interface may potentially serve as a precise, informative, biocompatible, and dual-mode neural interface for monitoring of both neuroelectrical and neurochemical activity at the single-cell level and even inside the cell. The authors demonstrate the utility of a neural chip with lithographically defined arrays of vertically aligned carbon nanofiber electrodes. The new device can be used to stimulate and/or monitor signals from brain tissue in vitro and for monitoring dynamic information of neuroplasticity both intracellularly and at the single cell level including neuroelectrical and neurochemical activities. Copyright © 2012 Elsevier Inc. All rights reserved.

Beyond good and evil: A putative continuum-sorting hypothesis for the functional role of proBDNF/BDNF-propeptide/mBDNF in antidepressant treatment.

PubMed

Diniz, Cassiano R A F; Casarotto, Plinio C; Resstel, Leonardo; Joca, Sâmia R L

2018-04-04

Depression and posttraumatic stress disorder are assumed to be maladaptive responses to stress and antidepressants are thought to counteract such responses by increasing BDNF (brain-derived neurotrophic factor) levels. BDNF acts through TrkB (tropomyosin-related receptor kinase B) and plays a central role in neuroplasticity. In contrast, both precursor proBDNF and BDNF propeptide (another metabolic product from proBDNF cleavage) have a high affinity to p75 receptor (p75R) and usually convey apoptosis and neuronal shrinkage. Although BDNF and proBDNF/propeptide apparently act in opposite ways, neuronal turnover and remodeling might be a final common way that both act to promote more effective neuronal networking, avoiding neuronal redundancy and the misleading effects of environmental contingencies. This review aims to provide a brief overview about the BDNF functional role in antidepressant action and about p75R and TrkB signaling to introduce the "continuum-sorting hypothesis." The resulting hypothesis suggests that both BDNF/proBDNF and BDNF/propeptide act as protagonists to fine-tune antidepressant-dependent neuroplasticity in crucial brain structures to modulate behavioral responses to stress. Copyright © 2018 Elsevier Ltd. All rights reserved.

Diverging effects of nicotine on motor learning performance: Improvement in deprived smokers and attenuation in non-smokers.

PubMed

Grundey, J; Amu, R; Batsikadze, G; Paulus, W; Nitsche, M A

2017-11-01

Nicotine modulates cognition and neuroplasticity in smokers and non-smokers. A possible mechanism for its effect on learning and memory performance is its impact on long-term potentiation (LTP) and long-term depression (LTD). As neuroplasticity is closely connected to learning processes, we aimed to explore the effect of nicotine in healthy, young smokers and non-smokers on performance of the serial reaction time task (SRTT), a sequential motor learning paradigm. 20 nicotine-deprived smokers and 20 non-smokers participated in the study and were exposed to nicotine or placebo medication. Deprived smokers under placebo medication displayed reduced performance in terms of reaction time and error rates compared to the non-smoking group. After application of nicotine, performance in smokers improved while it deteriorated in non-smokers. These results indicate a restituting effect of nicotine in smokers in terms of cognitive parameters. This sheds further light on the proposed mechanism of nicotine on learning processes, which might be linked to the addictive component of nicotine, the probability of relapse and thus needs also be addressed in cessation treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Importance and Difficulties of Pursuing rTMS Research in Acute Stroke

PubMed Central

Chappuis, Diane M.; Finkelstein, Marsha J.; Frost, Kate L.; Leuty, Lynette K.; McNulty, Allison L.; Oddsson, Lars I. E.; Seifert, Erin M.; Kimberley, Teresa J.

2017-01-01

Abstract Although much research has been done on repetitive transcranial magnetic stimulation (rTMS) in chronic stroke, only sparse research has been done in acute stroke despite the particularly rich potential for neuroplasticity in this stage. We attempted a preliminary clinical trial in one active, high-quality inpatient rehabilitation facility (IRF) in the -United States. But after enrolling only 4 patients in the grant period, the study was stopped because of low enrollment. The purpose of this paper is to offer a perspective describing the important physiologic rationale for including rTMS in the early phase of stroke, the reasons for our poor patient enrollment in our attempted study, and recommendations to help future studies succeed. We conclude that, if scientists and clinicians hope to enhance stroke outcomes, more attention must be directed to leveraging conventional rehabilitation with neuromodulation in the acute phase of stroke when the capacity for neuroplasticity is optimal. Difficulties with patient enrollment must be addressed by reassessing traditional inclusion and exclusion criteria. Factors that shorten patients’ length of stay in the IRF must also be reassessed at all policy-making levels to make ethical decisions that promote higher functional outcomes while retaining cost consciousness. PMID:28426872

Effects of palmitoylethanolamide and luteolin in an animal model of anxiety/depression.

PubMed

Crupi, Rosalia; Paterniti, Irene; Ahmad, Akbar; Campolo, Michela; Esposito, Emanuela; Cuzzocrea, Salvatore

2013-11-01

The antidepressant effect of a compound formed by co-ultramicronized palmitoylethanolamide (PEA) and luteolin (PEA+luteolin) was investigated in a mouse model of anxiety/depressive-like behavior. 129Sv/Ev mice were subjected to 6 weeks of corticosterone administration, and then behavior, neurogenesis, neuroplasticity, neurotrophic and apoptotic proteins expression were evaluated. The effect of PEA+luteolin compound treatment (1mg/kg, i.p.), on depression-like behaviour was assessed using different paradigms such as open field, novelty suppressed feeding, forced swim test and elevated plus maze. In particular in the open field, novelty suppressed feeding and elevated plus maze the time spent in the open arm was employed as an indicator of anxiety; forced swim test was used to evaluate the antidepressant capacity of PEA+luteolin on immobility time as an indicator of depression. Adult hippocampal neurogenesis and neuroplasticity were evaluated by immunohistochemical techniques; brain-derived neurotrophic factor and apoptotic protein (Bax and Bcl2) expression were studied by immunostaining and Western blot analysis. For the first time we demonstrated that PEA+luteolin compound exerts a significant antidepressant effect a low dose and may be considered as a novel therapeutic strategy in depression.

Modern pain neuroscience in clinical practice: applied to post-cancer, paediatric and sports-related pain.

PubMed

Malfliet, Anneleen; Leysen, Laurence; Pas, Roselien; Kuppens, Kevin; Nijs, Jo; Van Wilgen, Paul; Huysmans, Eva; Goudman, Lisa; Ickmans, Kelly

In the last decade, evidence regarding chronic pain has developed exponentially. Numerous studies show that many chronic pain populations show specific neuroplastic changes in the peripheral and central nervous system. These changes are reflected in clinical manifestations, like a generalized hypersensitivity of the somatosensory system. Besides a hypersensitivity of bottom-up nociceptive transmission, there is also evidence for top-down facilitation of pain due to malfunctioning of the endogenous descending nociceptive modulatory systems. These and other aspects of modern pain neuroscience are starting to be applied within daily clinical practice. However, currently the application of this knowledge is mostly limited to the general adult population with musculoskeletal problems, while evidence is getting stronger that also in other chronic pain populations these neuroplastic processes may contribute to the occurrence and persistence of the pain problem. Therefore, this masterclass article aims at giving an overview of the current modern pain neuroscience knowledge and its potential application in post-cancer, paediatric and sports-related pain problems. Copyright © 2017 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.

A single high dose of dexamethasone affects the phosphorylation state of glutamate AMPA receptors in the human limbic system

PubMed Central

Lopes, M W; Leal, R B; Guarnieri, R; Schwarzbold, M L; Hoeller, A; Diaz, A P; Boos, G L; Lin, K; Linhares, M N; Nunes, J C; Quevedo, J; Bortolotto, Z A; Markowitsch, H J; Lightman, S L; Walz, R

2016-01-01

Glucocorticoids (GC) released during stress response exert feedforward effects in the whole brain, but particularly in the limbic circuits that modulates cognition, emotion and behavior. GC are the most commonly prescribed anti-inflammatory and immunosuppressant medication worldwide and pharmacological GC treatment has been paralleled by the high incidence of acute and chronic neuropsychiatric side effects, which reinforces the brain sensitivity for GC. Synapses can be bi-directionally modifiable via potentiation (long-term potentiation, LTP) or depotentiation (long-term depression, LTD) of synaptic transmission efficacy, and the phosphorylation state of Ser831 and Ser845 sites, in the GluA1 subunit of the glutamate AMPA receptors, are a critical event for these synaptic neuroplasticity events. Through a quasi-randomized controlled study, we show that a single high dexamethasone dose significantly reduces in a dose-dependent manner the levels of GluA1-Ser831 phosphorylation in the amygdala resected during surgery for temporal lobe epilepsy. This is the first report demonstrating GC effects on key markers of synaptic neuroplasticity in the human limbic system. The results contribute to understanding how GC affects the human brain under physiologic and pharmacologic conditions. PMID:27959333

Anaesthetic neurotoxicity and neuroplasticity: an expert group report and statement based on the BJA Salzburg Seminar

PubMed Central

Jevtovic-Todorovic, V.; Absalom, A. R.; Blomgren, K.; Brambrink, A.; Crosby, G.; Culley, D. J.; Fiskum, G.; Giffard, R. G.; Herold, K. F.; Loepke, A. W.; Ma, D.; Orser, B. A.; Planel, E.; Slikker, W.; Soriano, S. G.; Stratmann, G.; Vutskits, L.; Xie, Z.; Hemmings, H. C.

2013-01-01

Although previously considered entirely reversible, general anaesthesia is now being viewed as a potentially significant risk to cognitive performance at both extremes of age. A large body of preclinical as well as some retrospective clinical evidence suggest that exposure to general anaesthesia could be detrimental to cognitive development in young subjects, and might also contribute to accelerated cognitive decline in the elderly. A group of experts in anaesthetic neuropharmacology and neurotoxicity convened in Salzburg, Austria for the BJA Salzburg Seminar on Anaesthetic Neurotoxicity and Neuroplasticity. This focused workshop was sponsored by the British Journal of Anaesthesia to review and critically assess currently available evidence from animal and human studies, and to consider the direction of future research. It was concluded that mounting evidence from preclinical studies reveals general anaesthetics to be powerful modulators of neuronal development and function, which could contribute to detrimental behavioural outcomes. However, definitive clinical data remain elusive. Since general anaesthesia often cannot be avoided regardless of patient age, it is important to understand the complex mechanisms and effects involved in anaesthesia-induced neurotoxicity, and to develop strategies for avoiding or limiting potential brain injury through evidence-based approaches. PMID:23722106

Neuroplastic changes in patients with schizophrenia undergoing cognitive remediation: triple-blind trial

PubMed Central

Ramsay, Ian S.; Nienow, Tasha M.; Marggraf, Matthew P.; MacDonald, Angus W.

2017-01-01

Background Patients with schizophrenia have shown cognitive improvements following cognitive remediation, but the neuroplastic changes that support these processes are not fully understood. Aims To use a triple-blind, placebo-controlled trial to examine neural activation before and after cognitive remediation or a computer skills training (CST) placebo (trial registration: NCT00995553)). Method Twenty-seven participants underwent functional magnetic resonance imaging before and after being randomised to either cognitive remediation intervention or CST. Participants completed two variants of the N-back task during scanning and were assessed on measures of cognition, functional capacity, community functioning and symptoms. Results We observed a group × time interaction in the left prefrontal cortex, wherein the cognitive remediation group showed increased activation. These changes correlated with improved task accuracy within the cognitive remediation group, whereas there was no relationship between changes in activation in untrained cognitive measures. Significant changes were not observed in other hypothesised areas for the cognitive remediation group. Conclusions We replicated the finding that cognitive remediation increases left lateral prefrontal activation during a working memory task in patients with schizophrenia, suggesting this may be an important neural target for these types of interventions. PMID:28153927

Neuroplastic changes in patients with schizophrenia undergoing cognitive remediation: triple-blind trial.

PubMed

Ramsay, Ian S; Nienow, Tasha M; Marggraf, Matthew P; MacDonald, Angus W

2017-03-01

Background Patients with schizophrenia have shown cognitive improvements following cognitive remediation, but the neuroplastic changes that support these processes are not fully understood. Aims To use a triple-blind, placebo-controlled trial to examine neural activation before and after cognitive remediation or a computer skills training (CST) placebo (trial registration: NCT00995553)). Method Twenty-seven participants underwent functional magnetic resonance imaging before and after being randomised to either cognitive remediation intervention or CST. Participants completed two variants of the N-back task during scanning and were assessed on measures of cognition, functional capacity, community functioning and symptoms. Results We observed a group × time interaction in the left prefrontal cortex, wherein the cognitive remediation group showed increased activation. These changes correlated with improved task accuracy within the cognitive remediation group, whereas there was no relationship between changes in activation in untrained cognitive measures. Significant changes were not observed in other hypothesised areas for the cognitive remediation group. Conclusions We replicated the finding that cognitive remediation increases left lateral prefrontal activation during a working memory task in patients with schizophrenia, suggesting this may be an important neural target for these types of interventions. © The Royal College of Psychiatrists 2017.

Sensory Innervation of the Nonspecialized Connective Tissues in the Low Back of the Rat

PubMed Central

Corey, Sarah M.; Vizzard, Margaret A.; Badger, Gary J.; Langevin, Helene M.

2011-01-01

Chronic musculoskeletal pain, including low back pain, is a worldwide debilitating condition; however, the mechanisms that underlie its development remain poorly understood. Pathological neuroplastic changes in the sensory innervation of connective tissue may contribute to the development of nonspecific chronic low back pain. Progress in understanding such potentially important abnormalities is hampered by limited knowledge of connective tissue's normal sensory innervation. The goal of this study was to evaluate and quantify the sensory nerve fibers terminating within the nonspecialized connective tissues in the low back of the rat. With 3-dimensional reconstructions of thick (30–80 μm) tissue sections we have for the first time conclusively identified sensory nerve fiber terminations within the collagen matrix of connective tissue in the low back. Using dye labeling techniques with Fast Blue, presumptive dorsal root ganglia cells that innervate the low back were identified. Of the Fast Blue-labeled cells, 60–88% also expressed calcitonin gene-related peptide (CGRP) immunoreactivity. Based on the immunolabeling with CGRP and the approximate size of these nerve fibers (≤2 μm) we hypothesize that they are Aδ or C fibers and thus may play a role in the development of chronic pain. PMID:21411968

Losing dexterity: patterns of impaired coordination of finger movements in musician’s dystonia

PubMed Central

Furuya, Shinichi; Tominaga, Kenta; Miyazaki, Fumio; Altenmüller, Eckart

2015-01-01

Extensive training can bring about highly-skilled action, but may also impair motor dexterity by producing involuntary movements and muscular cramping, as seen in focal dystonia (FD) and tremor. To elucidate the underlying neuroplastic mechanisms of FD, the present study addressed the organization of finger movements during piano performance in pianists suffering from the condition. Principal component (PC) analysis identified three patterns of fundamental joint coordination constituting finger movements in both patients and controls. The first two coordination patterns described less individuated movements between the “dystonic” finger and key-striking fingers for patients compared to controls. The third coordination pattern, representing the individuation of movements between the middle and ring fingers, was evident during a sequence of strikes with these fingers in controls, which was absent in the patients. Consequently, rhythmic variability of keystrokes was more pronounced during this sequence of strikes for the patients. A stepwise multiple-regression analysis further identified greater variability of keystrokes for individuals displaying less individuated movements between the affected and striking fingers. The findings suggest that FD alters dexterous joint coordination so as to lower independent control of finger movements, and thereby degrades fine motor control. PMID:26289433

Environmental Novelty is Associated with a Selective Increase in Fos Expression in the Output Elements of the Hippocampal Formation and the Perirhinal Cortex

ERIC Educational Resources Information Center

VanElzakker, Michael; Fevurly, Rebecca D.; Breindel, Tressa; Spencer, Robert L.

2008-01-01

If the hippocampus plays a role in the detection of novel environmental features, then novelty should be associated with altered hippocampal neural activity and perhaps also measures of neuroplasticity. We examined Fos protein expression within subregions of rat hippocampal formation as an indicator of recent increases in neuronal excitation and…

The tongue display unit (TDU) for electrotactile spatiotemporal pattern presentation.

PubMed

Kaczmarek, K A

2011-12-01

The Tongue Display Unit (TDU) is a 144-channel programmable pulse generator that delivers dc-balanced voltage pulses suitable for electrotactile (electrocutaneous) stimulation of the anterior-dorsal tongue, through a matrix of surface electrodes. This article reviews the theory of operation and a design overview of the TDU, as well as selected applications. These include sensory substitution, tactile information display and neurorehabilitation via induced neuroplasticity.

Brain Training in Children and Adolescents: Is It Scientifically Valid?

PubMed

Rossignoli-Palomeque, Teresa; Perez-Hernandez, Elena; González-Marqués, Javier

2018-01-01

Background: Brain training products are becoming increasingly popular for children and adolescents. Despite the marketing aimed at their use in the general population, these products may provide more benefits for specific neurologically impaired populations. A review of Brain Training (BT) products analyzing their efficacy while considering the methodological limitations of supporting research is required for practical applications. Method: searches were made of the PubMed database (until March 2017) for studies including: (1) empirical data on the use of brain training for children or adolescents and any effects on near transfer (NT) and/or far transfer (FT) and/or neuroplasticity, (2) use of brain training for cognitive training purposes, (3) commercially available training applications, (4) computer-based programs for children developed since the 1990s, and (5) relevant printed and peer-reviewed material. Results: Database searches yielded a total of 16,402 references, of which 70 met the inclusion criteria for the review. We classified programs in terms of neuroplasticity, near and far transfer, and long-term effects and their applied methodology. Regarding efficacy, only 10 studies (14.2%) have been found that support neuroplasticity, and the majority of brain training platforms claimed to be based on such concepts without providing any supporting scientific data. Thirty-six studies (51.4%) have shown far transfer (7 of them are non-independent) and only 11 (15.7%) maintained far transfer at follow-up. Considering the methodology, 40 studies (68.2%) were not randomized and controlled; for those randomized, only 9 studies (12.9%) were double-blind, and only 13 studies (18.6%) included active controls in their trials. Conclusion: Overall, few independent studies have found far transfer and long-term effects. The majority of independent results found only near transfer. There is a lack of double-blind randomized trials which include an active control group as well as a passive control to properly control for contaminant variables. Based on our results, Brain Training Programs as commercially available products are not as effective as first expected or as they promise in their advertisements.

[Are Visual Field Defects Reversible? - Visual Rehabilitation with Brains].

PubMed

Sabel, B A

2017-02-01

Visual field defects are considered irreversible because the retina and optic nerve do not regenerate. Nevertheless, there is some potential for recovery of the visual fields. This can be accomplished by the brain, which analyses and interprets visual information and is able to amplify residual signals through neuroplasticity. Neuroplasticity refers to the ability of the brain to change its own functional architecture by modulating synaptic efficacy. This is actually the neurobiological basis of normal learning. Plasticity is maintained throughout life and can be induced by repetitively stimulating (training) brain circuits. The question now arises as to how plasticity can be utilised to activate residual vision for the treatment of visual field loss. Just as in neurorehabilitation, visual field defects can be modulated by post-lesion plasticity to improve vision in glaucoma, diabetic retinopathy or optic neuropathy. Because almost all patients have some residual vision, the goal is to strengthen residual capacities by enhancing synaptic efficacy. New treatment paradigms have been tested in clinical studies, including vision restoration training and non-invasive alternating current stimulation. While vision training is a behavioural task to selectively stimulate "relative defects" with daily vision exercises for the duration of 6 months, treatment with alternating current stimulation (30 min. daily for 10 days) activates and synchronises the entire retina and brain. Though full restoration of vision is not possible, such treatments improve vision, both subjectively and objectively. This includes visual field enlargements, improved acuity and reaction time, improved orientation and vision related quality of life. About 70 % of the patients respond to the therapies and there are no serious adverse events. Physiological studies of the effect of alternating current stimulation using EEG and fMRI reveal massive local and global changes in the brain. These include local activation of the visual cortex and global reorganisation of neuronal brain networks. Because modulation of neuroplasticity can strengthen residual vision, the brain deserves a better reputation in ophthalmology for its role in visual rehabilitation. For patients, there is now more light at the end of the tunnel, because vision loss in some areas of the visual field defect is indeed reversible. Georg Thieme Verlag KG Stuttgart · New York.

Brain Training in Children and Adolescents: Is It Scientifically Valid?

PubMed Central

Rossignoli-Palomeque, Teresa; Perez-Hernandez, Elena; González-Marqués, Javier

2018-01-01

Background: Brain training products are becoming increasingly popular for children and adolescents. Despite the marketing aimed at their use in the general population, these products may provide more benefits for specific neurologically impaired populations. A review of Brain Training (BT) products analyzing their efficacy while considering the methodological limitations of supporting research is required for practical applications. Method: searches were made of the PubMed database (until March 2017) for studies including: (1) empirical data on the use of brain training for children or adolescents and any effects on near transfer (NT) and/or far transfer (FT) and/or neuroplasticity, (2) use of brain training for cognitive training purposes, (3) commercially available training applications, (4) computer-based programs for children developed since the 1990s, and (5) relevant printed and peer-reviewed material. Results: Database searches yielded a total of 16,402 references, of which 70 met the inclusion criteria for the review. We classified programs in terms of neuroplasticity, near and far transfer, and long-term effects and their applied methodology. Regarding efficacy, only 10 studies (14.2%) have been found that support neuroplasticity, and the majority of brain training platforms claimed to be based on such concepts without providing any supporting scientific data. Thirty-six studies (51.4%) have shown far transfer (7 of them are non-independent) and only 11 (15.7%) maintained far transfer at follow-up. Considering the methodology, 40 studies (68.2%) were not randomized and controlled; for those randomized, only 9 studies (12.9%) were double-blind, and only 13 studies (18.6%) included active controls in their trials. Conclusion: Overall, few independent studies have found far transfer and long-term effects. The majority of independent results found only near transfer. There is a lack of double-blind randomized trials which include an active control group as well as a passive control to properly control for contaminant variables. Based on our results, Brain Training Programs as commercially available products are not as effective as first expected or as they promise in their advertisements. PMID:29780336

Deletion of the Fractalkine Receptor, CX3CR1, Improves Endogenous Repair, Axon Sprouting, and Synaptogenesis after Spinal Cord Injury in Mice

PubMed Central

Wei, Ping; Guan, Zhen

2017-01-01

Impaired signaling via CX3CR1, the fractalkine receptor, promotes recovery after traumatic spinal contusion injury in mice, a benefit achieved in part by reducing macrophage-mediated injury at the lesion epicenter. Here, we tested the hypothesis that CX3CR1-dependent changes in microglia and macrophage functions also will enhance neuroplasticity, at and several segments below the injury epicenter. New data show that in the presence of inflammatory stimuli, CX3CR1-deficient (CX3CR1−/−) microglia and macrophages adopt a reparative phenotype and increase expression of genes that encode neurotrophic and gliogenic proteins. At the lesion epicenter (mid-thoracic spinal cord), the microenvironment created by CX3CR1−/− microglia/macrophages enhances NG2 cell responses, axon sparing, and sprouting of serotonergic axons. In lumbar spinal cord, inflammatory signaling is reduced in CX3CR1−/− microglia. This is associated with reduced dendritic pathology and improved axonal and synaptic plasticity on ventral horn motor neurons. Together, these data indicate that CX3CR1, a microglia-specific chemokine receptor, is a novel therapeutic target for enhancing neuroplasticity and recovery after SCI. Interventions that specifically target CX3CR1 could reduce the adverse effects of inflammation and augment activity-dependent plasticity and restoration of function. Indeed, limiting CX3CR1-dependent signaling could improve rehabilitation and spinal learning. SIGNIFICANCE STATEMENT Published data show that genetic deletion of CX3CR1, a microglia-specific chemokine receptor, promotes recovery after traumatic spinal cord injury in mice, a benefit achieved in part by reducing macrophage-mediated injury at the lesion epicenter. Data in the current manuscript indicate that CX3CR1 deletion changes microglia and macrophage function, creating a tissue microenvironment that enhances endogenous repair and indices of neuroplasticity, at and several segments below the injury epicenter. Interventions that specifically target CX3CR1 might be used in the future to reduce the adverse effects of intraspinal inflammation and augment activity-dependent plasticity (e.g., rehabilitation) and restoration of function. PMID:28264978

Brain changes due to hypoxia during light anaesthesia can be prevented by deepening anaesthesia; a study in rats

PubMed Central

Kalmar, Alain F.; Doorduin, Janine; Struys, Michel M. R. F.; Schoemaker, Regien G.; Absalom, Anthony R.

2018-01-01

In anaesthetic practice the risk of cerebral ischemic/hypoxic damage is thought to be attenuated by deep anaesthesia. The rationale is that deeper anaesthesia reduces cerebral oxygen demand more than light anaesthesia, thereby increasing the tolerance to ischemia or hypoxia. However, evidence to support this is scarce. We thus investigated the influence of light versus deep anaesthesia on the responses of rat brains to a period of hypoxia. In the first experiment we exposed adult male Wistar rats to deep or light propofol anaesthesia and then performed [18F]- Fludeoxyglucose (FDG) Positron Emission Tomography (PET) scans to verify the extent of cerebral metabolic suppression. In subsequent experiments, rats were subjected to light/deep propofol anaesthesia and then exposed to a period of hypoxia or ongoing normoxia (n = 9–11 per group). A further 5 rats, not exposed to anaesthesia or hypoxia, served as controls. Four days later a Novel Object Recognition (NOR) test was performed to assess mood and cognition. After another 4 days, the animals were sacrificed for later immunohistochemical analyses of neurogenesis/neuroplasticity (Doublecortin; DCX), Brain Derived Neurotrophic Factor (BDNF) expression and neuroinflammation (Ionized calcium-binding adaptor protein-1; Iba-1) in hippocampal and piriform cortex slices. The hippocampi of rats subjected to hypoxia during light anaesthesia showed lower DCX positivity, and therefore lower neurogenesis, but higher BDNF levels and microglia hyper-ramification. Exploration was reduced, but no significant effect on NOR was observed. In the piriform cortex, higher DCX positivity was observed, associated with neuroplasticity. All these effects were attenuated by deep anaesthesia. Deepening anaesthesia attenuated the brain changes associated with hypoxia. Hypoxia during light anaesthesia had a prolonged effect on the brain, but no impairment in cognitive function was observed. Although reduced hippocampal neurogenesis may be considered unfavourable, higher BDNF expression, associated with microglia hyper-ramification may suggest activation of repair mechanisms. Increased neuroplasticity observed in the piriform cortex supports this, and might reflect a prolonged state of alertness rather than damage. PMID:29451906

Low-Back Pain in Microgravity: Causes and Countermeasures

NASA Astrophysics Data System (ADS)

Snijders, C. J.; Richardson, C. A.

2005-06-01

Low-back pain (LBP) is common not only on Earth, but also in space.This is remarkable because, on Earth, LBP is ascribed mostly to heavy spinal loading.The Topical Team was established by ESA to answer the question "What is the aetiology of LBP during flight and what countermeasures may be developed?" The starting point for the Team's activities is a biomechanical model developed at the Erasmus Medical Centre in Rotterdam (NL) that describes the function of a deep-muscle corset to stabilise lumbar and pelvic joints. For spaceflight, the hypothesis was formulated that muscle atrophy and neuroplasticity in the absence of gravity loading destabilises the lumbopelvic area. The outcome of the Team activities is the development of a theory for the source of pain in microgravity that identifies in particular the iliolumbar ligaments.To help verify the theory,Team members were involved in the Berlin Bedrest Study and the Dutch Soyuz Mission. Based on the results of these studies, countermeasures can be developed and implemented.

Somatosensory tinnitus: Current evidence and future perspectives

PubMed Central

Ralli, Massimo; Greco, Antonio; Turchetta, Rosaria; Altissimi, Giancarlo; de Vincentiis, Marco; Cianfrone, Giancarlo

2017-01-01

In some individuals, tinnitus can be modulated by specific maneuvers of the temporomandibular joint, head and neck, eyes, and limbs. Neuroplasticity seems to play a central role in this capacity for modulation, suggesting that abnormal interactions between the sensory modalities, sensorimotor systems, and neurocognitive and neuroemotional networks may contribute to the development of somatosensory tinnitus. Current evidence supports a link between somatic disorders and higher modulation of tinnitus, especially in patients with a normal hearing threshold. Patients with tinnitus who have somatic disorders seems to have a higher chance of modulating their tinnitus with somatic maneuvers; consistent improvements in tinnitus symptoms have been observed in patients with temporomandibular joint disease following targeted therapy for temporomandibular disorders. Somatosensory tinnitus is often overlooked by otolaryngologists and not fully investigated during the diagnostic process. Somatic disorders, when identified and treated, can be a valid therapeutic target for tinnitus; however, somatic screening of subjects for somatosensory tinnitus is imperative for correct selection of patients who would benefit from a multidisciplinary somatic approach. PMID:28553764

Somatosensory tinnitus: Current evidence and future perspectives.

PubMed

Ralli, Massimo; Greco, Antonio; Turchetta, Rosaria; Altissimi, Giancarlo; de Vincentiis, Marco; Cianfrone, Giancarlo

2017-06-01

In some individuals, tinnitus can be modulated by specific maneuvers of the temporomandibular joint, head and neck, eyes, and limbs. Neuroplasticity seems to play a central role in this capacity for modulation, suggesting that abnormal interactions between the sensory modalities, sensorimotor systems, and neurocognitive and neuroemotional networks may contribute to the development of somatosensory tinnitus. Current evidence supports a link between somatic disorders and higher modulation of tinnitus, especially in patients with a normal hearing threshold. Patients with tinnitus who have somatic disorders seems to have a higher chance of modulating their tinnitus with somatic maneuvers; consistent improvements in tinnitus symptoms have been observed in patients with temporomandibular joint disease following targeted therapy for temporomandibular disorders. Somatosensory tinnitus is often overlooked by otolaryngologists and not fully investigated during the diagnostic process. Somatic disorders, when identified and treated, can be a valid therapeutic target for tinnitus; however, somatic screening of subjects for somatosensory tinnitus is imperative for correct selection of patients who would benefit from a multidisciplinary somatic approach.

A DEVELOPMENTAL COMPARISON OF THE NEUROBEHAVIORAL EFFECTS OF ECSTASY (MDMA)

PubMed Central

Piper, Brian J.

2007-01-01

The entactogen ±3,4-methylenedioxymethamphetamine (MDMA or ecstasy) is a popular recreational drug among college, high school, and, occasionally, middle school students. Preclinical research examining the acute and long-term effects of MDMA has predominately been conducted in reproductively mature subjects but there has been increasing interest in adolescent and in utero exposure. This review examines the acute and long-term responses to MDMA during perinatal, adolescent, and adult periods. The ability of MDMA to alter core body temperature emerges gradually during ontogeny while a reduction in body weight is evident at all ages. Learning and working-memory are also altered independent of the developmental stage of exposure. Current evidence suggests adults are more sensitive to the long-term serotonin depletions following MDMA but younger ages also exhibit substantial and rapid neuroplasticity. Sexually dimorphic MDMA responses have been identified for the acute hyperthermic and motoric effects of MDMA with pubescent males being especially susceptible. Several physiological, behavioral, and neurochemical MDMA issues requiring further study are also outlined. PMID:17174068

Functional Interplay between Small Non-Coding RNAs and RNA Modification in the Brain.

PubMed

Leighton, Laura J; Bredy, Timothy W

2018-06-07

Small non-coding RNAs are essential for transcription, translation and gene regulation in all cell types, but are particularly important in neurons, with known roles in neurodevelopment, neuroplasticity and neurological disease. Many small non-coding RNAs are directly involved in the post-transcriptional modification of other RNA species, while others are themselves substrates for modification, or are functionally modulated by modification of their target RNAs. In this review, we explore the known and potential functions of several distinct classes of small non-coding RNAs in the mammalian brain, focusing on the newly recognised interplay between the epitranscriptome and the activity of small RNAs. We discuss the potential for this relationship to influence the spatial and temporal dynamics of gene activation in the brain, and predict that further research in the field of epitranscriptomics will identify interactions between small RNAs and RNA modifications which are essential for higher order brain functions such as learning and memory.

Neurobiology of Adolescent Substance Use and Addictive Behaviors: Prevention and Treatment Implications

PubMed Central

Hammond, Christopher J.; Mayes, Linda C.; Potenza, Marc N.

2015-01-01

Psychoactive substance and nonsubstance/behavioral addictions are major public health concerns associated with significant societal cost. Adolescence is a period of dynamic biologic, psychological, and behavioral changes. Adolescence is also associated with an increased risk for substance use and addictive disorders. During adolescence, developmental changes in neural circuitry of reward processing, motivation, cognitive control, and stress may contribute to vulnerability for increased levels of engagement in substance use and nonsubstance addictive behaviors. Current biologic models of adolescent vulnerability for addictions incorporate existing data on allostatic changes in function and structure of the midbrain dopaminergic system, stress-associated neuroplasticity, and maturational imbalances between cognitive control and reward reactivity. When characterizing adolescent vulnerability, identifying subgroups of adolescents at high risk for addictive behaviors is a major goal of the addiction field. Genetics, epigenetics, and intermediate phenotypes/endophenotypes may assist in characterizing children and adolescents at risk. Improved understanding of the neurobiology of adolescence and addiction vulnerability has the potential to refine screening, enhance prevention and intervention strategies, and inform public policy. PMID:25022184

Endurance Exercise as an “Endogenous” Neuro-enhancement Strategy to Facilitate Motor Learning

PubMed Central

Taubert, Marco; Villringer, Arno; Lehmann, Nico

2015-01-01

Endurance exercise improves cardiovascular and musculoskeletal function and may also increase the information processing capacities of the brain. Animal and human research from the past decade demonstrated widespread exercise effects on brain structure and function at the systems-, cellular-, and molecular level of brain organization. These neurobiological mechanisms may explain the well-established positive influence of exercise on performance in various behavioral domains but also its contribution to improved skill learning and neuroplasticity. With respect to the latter, only few empirical and theoretical studies are available to date. The aim of this review is (i) to summarize the existing neurobiological and behavioral evidence arguing for endurance exercise-induced improvements in motor learning and (ii) to develop hypotheses about the mechanistic link between exercise and improved learning. We identify major knowledge gaps that need to be addressed by future research projects to advance our understanding of how exercise should be organized to optimize motor learning. PMID:26834602

Postinflammatory visceral sensitivity and pain mechanisms.

PubMed

Vergnolle, N

2008-05-01

The inflammatory reaction is normally tightly regulated, and as soon as the original insult has been cleared, a resolution phase starts that aims at leading the tissues back to a normal physiological state. However, after intestinal inflammation, a number of patients develop postinflammatory hypersensitivity symptoms, which can be defined as an excessive sensitivity to gut nociceptive stimulation. The pain experienced by those patients has been largely studied in the context of postinfectious intestinal diseases. The mechanisms of postinflammatory persistent visceral pain involve peripheral and central neuroplastic changes, low-grade chronic inflammation that sensitizes visceral afferent pathways and sensitization of non-neuronal resident cells of the gut. Several molecular determinants such as neurokinins, serotonin, proteases and voltage-gated ion channels seem to play a significant role in the control of postinflammatory visceral sensation. This review tries to give insights into the mechanisms of persistent visceral pain following the resolution of intestinal inflammation and tries to identify what needs to be done to further advance the field of postinflammatory hypersensitivity clinical management.

Plasticity in neuromagnetic cortical responses suggests enhanced auditory object representation

PubMed Central

2013-01-01

Background Auditory perceptual learning persistently modifies neural networks in the central nervous system. Central auditory processing comprises a hierarchy of sound analysis and integration, which transforms an acoustical signal into a meaningful object for perception. Based on latencies and source locations of auditory evoked responses, we investigated which stage of central processing undergoes neuroplastic changes when gaining auditory experience during passive listening and active perceptual training. Young healthy volunteers participated in a five-day training program to identify two pre-voiced versions of the stop-consonant syllable ‘ba’, which is an unusual speech sound to English listeners. Magnetoencephalographic (MEG) brain responses were recorded during two pre-training and one post-training sessions. Underlying cortical sources were localized, and the temporal dynamics of auditory evoked responses were analyzed. Results After both passive listening and active training, the amplitude of the P2m wave with latency of 200 ms increased considerably. By this latency, the integration of stimulus features into an auditory object for further conscious perception is considered to be complete. Therefore the P2m changes were discussed in the light of auditory object representation. Moreover, P2m sources were localized in anterior auditory association cortex, which is part of the antero-ventral pathway for object identification. The amplitude of the earlier N1m wave, which is related to processing of sensory information, did not change over the time course of the study. Conclusion The P2m amplitude increase and its persistence over time constitute a neuroplastic change. The P2m gain likely reflects enhanced object representation after stimulus experience and training, which enables listeners to improve their ability for scrutinizing fine differences in pre-voicing time. Different trajectories of brain and behaviour changes suggest that the preceding effect of a P2m increase relates to brain processes, which are necessary precursors of perceptual learning. Cautious discussion is required when interpreting the finding of a P2 amplitude increase between recordings before and after training and learning. PMID:24314010

Harnessing Neuroplasticity to Enhance Functional Recovery in Allogeneic Hand Transplant and Heterotopic Hand Replant Recipients

DTIC Science & Technology

2016-10-01

evidence that limb amputation not only impacts the peripheral nervous system but also the brain, and tailoring interventions accordingly. 2...recent discoveries in neuroscience to facilitate long-term, experience-dependent adaptations within the brain’s sensory and motor systems . The current...governments, schools or school systems , or other organizations (foreign or domestic) – that were involved with the project. Partner organizations may have

Pharmacological and Behavioral Enhancement of Neuroplasticity in the MPTP-Lesioned Mouse and Nonhuman Primate

DTIC Science & Technology

2006-05-01

and significant changes in the pattern of expression of ionotropic glutamate receptors in the cortex and striatum. In addition, exercise resulted in...transporter number; (2) phos- phorylation activated through glutamate receptors such as the mGluR5 metabotropic receptor ; and (3) internaliza- tion...dopamine transporter activity by the metabotropic glutamate receptor mGluR5 in rat striatal synaptosomes through phosphorylation mediated processes

Harnessing Neuroplasticity to Promote Rehabilitation: CI Therapy for TBI

DTIC Science & Technology

2016-10-01

scheduled plus 33 to be enrolled, because we assume that the proportion of withdrawals will be the same as experienced to date, i.e., 24%. This plan will...period? Victor Mark, Investigator Interactive Immersive Virtual Reality Walking for SCI Neuropathic Pain (Trost) 0.24 calendar months Kim Cerise...Direct Costs: $149,999 This project designs and test an immersive virtual reality treatment method to control neuropathic pain following traumatic spinal

Antidepressant-like effects of erythropoietin: a focus on behavioural and hippocampal processes.

PubMed

Osborn, Meagan; Rustom, Nazneen; Clarke, Melanie; Litteljohn, Darcy; Rudyk, Chris; Anisman, Hymie; Hayley, Shawn

2013-01-01

Depression is a chronic and debilitating condition with a significant degree of relapse and treatment resistance that could stem, at least in part, from disturbances of neuroplasticity. This has led to an increased focus on treatment strategies that target brain derived neurotrophic factor (BDNF), synaptic plasticity and adult neurogenesis. In the current study we aimed to assess whether erythropoietin (EPO) would have antidepressant-like effects given its already established pro-trophic actions. In particular, we assessed whether EPO would diminish the deleterious effects of a social stressor in mice. Indeed, EPO induced anxiolytic and antidepressant-like responses in a forced swim test, open field, elevated-plus maze, and a novelty test, and appeared to blunt some of the negative behavioural effects of a social stressor. Furthermore, EPO promoted adult hippocampal neurogenesis, an important feature of effective antidepressants. Finally, a separate study using the mTOR inhibitor rapamycin revealed that antagonizing this pathway prevented the impact of EPO upon forced swim performance. These data are consistent with previous findings showing that the mTOR pathway and its neurogenic and synaptogenic effects might mediate the behavioral consequences of antidepressant agents. Our findings further highlight EPO as a possible adjunct treatment for affective disorders, as well as other stressor associated disorders of impaired neuroplasticity.

Cognitive and Neuroplasticity Mechanisms by Which Congenital or Early Blindness May Confer a Protective Effect Against Schizophrenia

PubMed Central

Silverstein, Steven M.; Wang, Yushi; Keane, Brian P.

2013-01-01

Several authors have noted that there are no reported cases of people with schizophrenia who were born blind or who developed blindness shortly after birth, suggesting that congenital or early (C/E) blindness may serve as a protective factor against schizophrenia. By what mechanisms might this effect operate? Here, we hypothesize that C/E blindness offers protection by strengthening cognitive functions whose impairment characterizes schizophrenia, and by constraining cognitive processes that exhibit excessive flexibility in schizophrenia. After briefly summarizing evidence that schizophrenia is fundamentally a cognitive disorder, we review areas of perceptual and cognitive function that are both impaired in the illness and augmented in C/E blindness, as compared to healthy sighted individuals. We next discuss: (1) the role of neuroplasticity in driving these cognitive changes in C/E blindness; (2) evidence that C/E blindness does not confer protective effects against other mental disorders; and (3) evidence that other forms of C/E sensory loss (e.g., deafness) do not reduce the risk of schizophrenia. We conclude by discussing implications of these data for designing cognitive training interventions to reduce schizophrenia-related cognitive impairment, and perhaps to reduce the likelihood of the development of the disorder itself. PMID:23349646

STRESS RISK FACTORS AND STRESS-RELATED PATHOLOGY: NEUROPLASTICITY, EPIGENETICS AND ENDOPHENOTYPES

PubMed Central

Radley, Jason J.; Kabbaj, Mohamed; Jacobson, Lauren; Heydendael, Willem; Yehuda, Rachel; Herman, James P.

2013-01-01

This review highlights a symposium on stress risk factors and stress susceptibility, presented at the Neurobiology of Stress workshop in Boulder, Colorado, June 2010. This symposium addressed factors linking stress plasticity and reactivity to stress pathology in animal models and in humans. Dr. Jason Radley discussed studies demonstrating prefrontal cortical neuroplasticity and prefrontal control of hypothalamo-pituitary-adrenocortical axis function in rat, highlighting emerging evidence for a critical role of this region in normal and pathological stress integration. Dr. Mohamed Kabbaj summarized his studies of possible epigenetic mechanisms underlying behavioral differences in rat populations bred for differential stress reactivity. Dr. Lauren Jacobson described studies using a mouse model to explore the diverse actions of antidepressant action in brain, suggesting mechanisms whereby antidepressants may be differentially effective in treating specific depression endophenotypes. Dr. Rachel Yehuda discussed the role of glucocorticoids in post-traumatic stress disorder (PTSD), indicating that low cortisol may be a trait that predisposes the individual to development of the disorder. Furthermore, she presented evidence indicating that traumatic events can have transgenerational impact on cortisol reactivity and development of PTSD symptoms. Together, the symposium highlighted emerging themes regarding the role of brain reorganization, individual differences and epigenetics in determining stress plasticity and pathology. PMID:21848436

Meditation-induced neuroplastic changes in amygdala activity during negative affective processing.

PubMed

Leung, Mei-Kei; Lau, Way K W; Chan, Chetwyn C H; Wong, Samuel S Y; Fung, Annis L C; Lee, Tatia M C

2018-06-01

Recent evidence suggests that the effects of meditation practice on affective processing and resilience have the potential to induce neuroplastic changes within the amygdala. Notably, literature speculates that meditation training may reduce amygdala activity during negative affective processing. Nonetheless, studies have thus far not verified this speculation. In this longitudinal study, participants (N = 21, 9 men) were trained in awareness-based compassion meditation (ABCM) or matched relaxation training. The effects of meditation training on amygdala activity were examined during passive viewing of affective and neutral stimuli in a non-meditative state. We found that the ABCM group exhibited significantly reduced anxiety and right amygdala activity during negative emotion processing than the relaxation group. Furthermore, ABCM participants who performed more compassion practice had stronger right amygdala activity reduction during negative emotion processing. The lower right amygdala activity after ABCM training may be associated with a general reduction in reactivity and distress. As all participants performed the emotion processing task in a non-meditative state, it appears likely that the changes in right amygdala activity are carried over from the meditation practice into the non-meditative state. These findings suggest that the distress-reducing effects of meditation practice on affective processing may transfer to ordinary states, which have important implications on stress management.

Neural Plastic Effects of Cognitive Training on Aging Brain

PubMed Central

Leung, Natalie T. Y.; Tam, Helena M. K.; Chu, Leung W.; Kwok, Timothy C. Y.; Chan, Felix; Lam, Linda C. W.; Woo, Jean; Lee, Tatia M. C.

2015-01-01

Increasing research has evidenced that our brain retains a capacity to change in response to experience until late adulthood. This implies that cognitive training can possibly ameliorate age-associated cognitive decline by inducing training-specific neural plastic changes at both neural and behavioral levels. This longitudinal study examined the behavioral effects of a systematic thirteen-week cognitive training program on attention and working memory of older adults who were at risk of cognitive decline. These older adults were randomly assigned to the Cognitive Training Group (n = 109) and the Active Control Group (n = 100). Findings clearly indicated that training induced improvement in auditory and visual-spatial attention and working memory. The training effect was specific to the experience provided because no significant difference in verbal and visual-spatial memory between the two groups was observed. This pattern of findings is consistent with the prediction and the principle of experience-dependent neuroplasticity. Findings of our study provided further support to the notion that the neural plastic potential continues until older age. The baseline cognitive status did not correlate with pre- versus posttraining changes to any cognitive variables studied, suggesting that the initial cognitive status may not limit the neuroplastic potential of the brain at an old age. PMID:26417460

Combining computerized social cognitive training with neuroplasticity-based auditory training in schizophrenia.

PubMed

Sacks, Stephanie; Fisher, Melissa; Garrett, Coleman; Alexander, Phillip; Holland, Christine; Rose, Demian; Hooker, Christine; Vinogradov, Sophia

2013-01-01

Social cognitive deficits are an important treatment target in schizophrenia, but it is unclear to what degree they require specialized interventions and which specific components of behavioral interventions are effective. In this pilot study, we explored the effects of a novel computerized neuroplasticity-based auditory training delivered in conjunction with computerized social cognition training (SCT) in patients with schizophrenia. Nineteen clinically stable schizophrenia subjects performed 50 hours of computerized exercises that place implicit, increasing demands on auditory perception, plus 12 hours of computerized training in emotion identification, social perception, and theory of mind tasks. All subjects were assessed with MATRICS-recommended measures of neurocognition and social cognition, plus a measure of self-referential source memory before and after the computerized training. Subjects showed significant improvements on multiple measures of neurocognition. Additionally, subjects showed significant gains on measures of social cognition, including the MSCEIT Perceiving Emotions, MSCEIT Managing Emotions, and self-referential source memory, plus a significant decrease in positive symptoms. Computerized training of auditory processing/verbal learning in schizophrenia results in significant basic neurocognitive gains. Further, addition of computerized social cognition training results in significant gains in several social cognitive outcome measures. Computerized cognitive training that directly targets social cognitive processes can drive improvements in these crucial functions.

Corticospinal Plasticity in Bilateral Primary Motor Cortices Induced by Paired Associative Stimulation to the Dominant Hemisphere Does Not Differ between Young and Older Adults

PubMed Central

Dickins, Daina S. E.

2017-01-01

Older adults have been shown to exhibit a reduction in the lateralization of neural activity. Although neuroplasticity induced by noninvasive brain stimulation has been reported to be attenuated in the targeted motor cortex of older adults, it remains possible that the plasticity effects may instead manifest in a more distributed (bilateral) network. Furthermore, attention, which modulates neuroplasticity in young adults, may influence these effects. To address these questions, plasticity was induced in young (19–32 years) and older (65–78 years) adults using transcranial magnetic stimulation (TMS) paired with peripheral nerve stimulation. The plasticity effects induced by this paired associative stimulation (PAS) protocol in the targeted and nontargeted hemispheres were probed using TMS-induced motor-evoked potentials (MEPs) recorded from the abductor pollicis brevis (APB) muscle of each hand. PAS-induced effects were highly variable across individuals, with only half of the participants in each group demonstrating the expected increase in MEP amplitude. Contrary to predictions, however, PAS-induced corticospinal plasticity manifests predominately in the targeted hemisphere for both young and older adults. Attention to the target hand did not enhance corticospinal plasticity. The results suggest that plasticity does not manifest differently across bilateral corticospinal pathways between young and older adults. PMID:29147586

Involvement of the K+-Cl- co-transporter KCC2 in the sensitization to morphine-induced hyperlocomotion under chronic treatment with zolpidem in the mesolimbic system.

PubMed

Shibasaki, Masahiro; Masukawa, Daiki; Ishii, Kazunori; Yamagishi, Yui; Mori, Tomohisa; Suzuki, Tsutomu

2013-06-01

Benzodiazepines are commonly used as sedatives, sleeping aids, and anti-anxiety drugs. However, chronic treatment with benzodiazepines is known to induce dependence, which is considered related to neuroplastic changes in the mesolimbic system. This study investigated the involvement of K(+) -Cl(-) co-transporter 2 (KCC2) in the sensitization to morphine-induced hyperlocomotion after chronic treatment with zolpidem [a selective agonist of γ-aminobutyric acid A-type receptor (GABAA R) α1 subunit]. In this study, chronic treatment with zolpidem enhanced morphine-induced hyperlocomotion, which is accompanied by the up-regulation of KCC2 in the limbic forebrain. We also found that chronic treatment with zolpidem induced the down-regulation of protein phosphatase-1 (PP-1) as well as the up-regulation of phosphorylated protein kinase C γ (pPKCγ). Furthermore, PP-1 directly associated with KCC2 and pPKCγ, whereas pPKCγ did not associate with KCC2. On the other hand, pre-treatment with furosemide (a KCC2 inhibitor) suppressed the enhancing effects of zolpidem on morphine-induced hyperlocomotion. These results suggest that the mesolimbic dopaminergic system could be amenable to neuroplastic change through a pPKCγ-PP-1-KCC2 pathway by chronic treatment with zolpidem. © 2013 International Society for Neurochemistry.

Consciousness, Plasticity, and Connectomics: The Role of Intersubjectivity in Human Cognition

PubMed Central

Allen, Micah; Williams, Gary

2011-01-01

Consciousness is typically construed as being explainable purely in terms of either private, raw feels or higher-order, reflective representations. In contrast to this false dichotomy, we propose a new view of consciousness as an interactive, plastic phenomenon open to sociocultural influence. We take up our account of consciousness from the observation of radical cortical neuroplasticity in human development. Accordingly, we draw upon recent research on macroscopic neural networks, including the “default mode,” to illustrate cases in which an individual's particular “connectome” is shaped by encultured social practices that depend upon and influence phenomenal and reflective consciousness. On our account, the dynamically interacting connectivity of these networks bring about important individual differences in conscious experience and determine what is “present” in consciousness. Further, we argue that the organization of the brain into discrete anti-correlated networks supports the phenomenological distinction of prereflective and reflective consciousness, but we emphasize that this finding must be interpreted in light of the dynamic, category-resistant nature of consciousness. Our account motivates philosophical and empirical hypotheses regarding the appropriate time-scale and function of neuroplastic adaptation, the relation of high and low-frequency neural activity to consciousness and cognitive plasticity, and the role of ritual social practices in neural development and cognitive function. PMID:21687435

Emergence of Virtual Reality as a Tool for Upper Limb Rehabilitation: Incorporation of Motor Control and Motor Learning Principles

PubMed Central

Weiss, Patrice L.; Keshner, Emily A.

2015-01-01

The primary focus of rehabilitation for individuals with loss of upper limb movement as a result of acquired brain injury is the relearning of specific motor skills and daily tasks. This relearning is essential because the loss of upper limb movement often results in a reduced quality of life. Although rehabilitation strives to take advantage of neuroplastic processes during recovery, results of traditional approaches to upper limb rehabilitation have not entirely met this goal. In contrast, enriched training tasks, simulated with a wide range of low- to high-end virtual reality–based simulations, can be used to provide meaningful, repetitive practice together with salient feedback, thereby maximizing neuroplastic processes via motor learning and motor recovery. Such enriched virtual environments have the potential to optimize motor learning by manipulating practice conditions that explicitly engage motivational, cognitive, motor control, and sensory feedback–based learning mechanisms. The objectives of this article are to review motor control and motor learning principles, to discuss how they can be exploited by virtual reality training environments, and to provide evidence concerning current applications for upper limb motor recovery. The limitations of the current technologies with respect to their effectiveness and transfer of learning to daily life tasks also are discussed. PMID:25212522

Systematic evaluation of the impact of stimulation intensity on neuroplastic after-effects induced by transcranial direct current stimulation.

PubMed

Jamil, Asif; Batsikadze, Giorgi; Kuo, Hsiao-I; Labruna, Ludovica; Hasan, Alkomiet; Paulus, Walter; Nitsche, Michael A

2017-02-15

Applications of transcranial direct current stimulation to modulate human neuroplasticity have increased in research and clinical settings. However, the need for longer-lasting effects, combined with marked inter-individual variability, necessitates a deeper understanding of the relationship between stimulation parameters and physiological effects. We systematically investigated the full DC intensity range (0.5-2.0 mA) for both anodal and cathodal tDCS in a sham-controlled repeated measures design, monitoring changes in motor-cortical excitability via transcranial magnetic stimulation up to 2 h after stimulation. For both tDCS polarities, the excitability after-effects did not linearly correlate with increasing DC intensity; effects of lower intensities (0.5, 1.0 mA) showed equal, if not greater effects in motor-cortical excitability. Further, while intra-individual responses showed good reliability, inter-individual sensitivity to TMS accounted for a modest percentage of the variance in the early after-effects of 1.0 mA anodal tDCS, which may be of practical relevance for future optimizations. Contemporary non-invasive neuromodulatory techniques, such as transcranial direct current stimulation (tDCS), have shown promising potential in both restituting impairments in cortical physiology in clinical settings, as well as modulating cognitive abilities in the healthy population. However, neuroplastic after-effects of tDCS are highly dependent on stimulation parameters, relatively short lasting, and not expectedly uniform between individuals. The present study systematically investigates the full range of current intensity between 0.5 and 2.0 mA on left primary motor cortex (M1) plasticity, as well as the impact of individual-level covariates on explaining inter-individual variability. Thirty-eight healthy subjects were divided into groups of anodal and cathodal tDCS. Five DC intensities (sham, 0.5, 1.0, 1.5 and 2.0 mA) were investigated in separate sessions. Using transcranial magnetic stimulation (TMS), 25 motor-evoked potentials (MEPs) were recorded before, and 10 time points up to 2 h following 15 min of tDCS. Repeated-measures ANOVAs indicated a main effect of intensity for both anodal and cathodal tDCS. With anodal tDCS, all active intensities resulted in equivalent facilitatory effects relative to sham while for cathodal tDCS, only 1.0 mA resulted in sustained excitability diminution. An additional experiment conducted to assess intra-individual variability revealed generally good reliability of 1.0 mA anodal tDCS (ICC(2,1) = 0.74 over the first 30 min). A post hoc analysis to discern sources of inter-individual variability confirmed a previous finding in which individual TMS SI 1mV (stimulus intensity for 1 mV MEP amplitude) sensitivity correlated negatively with 1.0 mA anodal tDCS effects on excitability. Our study thus provides further insights on the extent of non-linear intensity-dependent neuroplastic after-effects of anodal and cathodal tDCS. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

First Language Attrition Induces Changes in Online Morphosyntactic Processing and Re-Analysis: An ERP Study of Number Agreement in Complex Italian Sentences

ERIC Educational Resources Information Center

Kasparian, Kristina; Vespignani, Francesco; Steinhauer, Karsten

2017-01-01

First language (L1) attrition in adulthood offers new insight on neuroplasticity and the role of language experience in shaping neurocognitive responses to language. Attriters are multilinguals for whom advancing L2 proficiency comes at the cost of the L1, as they experience a shift in exposure and dominance (e.g., due to immigration). To date,…

A Translational Neuroscience Approach to Understanding the Development of Social Anxiety Disorder and its Pathophysiology

PubMed Central

Fox, Andrew S.; Kalin, Ned H.

2014-01-01

This review brings together recent research from molecular, neural circuit, animal model, and human studies to understand the neurodevelopmental mechanisms underlying Social Anxiety Disorder (SAD). SAD is common, debilitating, and often leads to further psychopathology. Numerous studies demonstrate that extremely behaviorally inhibited and temperamentally anxious young children are at marked risk to develop SAD. Recent work in human and nonhuman primates has identified a distributed brain network that underlies early-life anxiety including: central nucleus of the amygdala, anterior hippocampus and orbitofrontal cortex. Moreover, studies in nonhuman primates demonstrate that alterations in this circuit are trait-like in that they are stable over time and across contexts. Importantly, the components of this circuit are differentially influenced by heritable and environmental factors and specific lesion studies demonstrate a causal role for multiple components of the circuit. Molecular studies in rodents and primates are pointing to disrupted neurodevelopmental and neuroplastic processes within critical components of the early-life dispositional anxiety neural circuit. The possibility of identifying an early-life at-risk phenotype, along with an understanding of its neurobiology, provides an unusual opportunity to conceptualize novel preventive intervention strategies aimed at reducing the suffering of anxious children and preventing them from developing further psychopathology. PMID:25157566

A translational neuroscience approach to understanding the development of social anxiety disorder and its pathophysiology.

PubMed

Fox, Andrew S; Kalin, Ned H

2014-11-01

This review brings together recent research from molecular, neural circuit, animal model, and human studies to help understand the neurodevelopmental mechanisms underlying social anxiety disorder. Social anxiety disorder is common and debilitating, and it often leads to further psychopathology. Numerous studies have demonstrated that extremely behaviorally inhibited and temperamentally anxious young children are at marked risk of developing social anxiety disorder. Recent work in human and nonhuman primates has identified a distributed brain network that underlies early-life anxiety including the central nucleus of the amygdala, the anterior hippocampus, and the orbitofrontal cortex. Studies in nonhuman primates have demonstrated that alterations in this circuit are trait-like in that they are stable over time and across contexts. Notably, the components of this circuit are differentially influenced by heritable and environmental factors, and specific lesion studies have demonstrated a causal role for multiple components of the circuit. Molecular studies in rodents and primates point to disrupted neurodevelopmental and neuroplastic processes within critical components of the early-life dispositional anxiety neural circuit. The possibility of identifying an early-life at-risk phenotype, along with an understanding of its neurobiology, provides an unusual opportunity to conceptualize novel preventive intervention strategies aimed at reducing the suffering of anxious children and preventing them from developing further psychopathology.

Old friends in new constellations--the hematopoetic growth factors G-CSF, GM-CSF, and EPO for the treatment of neurological diseases.

PubMed

Maurer, M H; Schäbitz, W-R; Schneider, A

2008-01-01

Currently, growth factors which have been identified in hematopoiesis and angiogenesis are re-considered as therapeutical agents in a number of neurological diseases, mainly neurodegenerative disorders like Parkinson's Disease, amyotrophic lateral sclerosis (ALS), or cerebrovascular events such as stroke. Among these growth factors, erythropoietin (EPO) and granulocyte colony-stimulating growth factor (G-CSF) are the most prominent. With regard to neurological disease, EPO has been tested in clinical trials for potential use in stroke, schizophrenia, and addiction, G-CSF is currently under clinical investigation for stroke treatment. The major advantage of these growth factors is their well-described pharmacological behavior and their clinical use over several years. A number of mechanisms of action in the CNS have been identified that are probably important for the beneficial action of these factors in animal models of disease, the most relevant relating to neuroprotection, neuroplasticity and stem cell growth and differentiation. In this review, we will discuss the current efforts and prerequisites of novel growth factor therapies for neurodegenerative diseases with regard to their possible mechanism of action on the molecular level and their effects on brain-derived stem cell populations. Additionally, we will describe the necessities for future research before such therapies can be envisioned.

Chotosan (Diaoteng San)-induced improvement of cognitive deficits in senescence-accelerated mouse (SAMP8) involves the amelioration of angiogenic/neurotrophic factors and neuroplasticity systems in the brain

PubMed Central

2011-01-01

Background Chotosan (CTS, Diaoteng San), a Kampo medicine (ie Chinese medicine) formula, is reportedly effective in the treatment of patients with cerebral ischemic insults. This study aims to evaluate the therapeutic potential of CTS in cognitive deficits and investigates the effects and molecular mechanism(s) of CTS on learning and memory deficits and emotional abnormality in an animal aging model, namely 20-week-old senescence-accelerated prone mice (SAMP8), with and without a transient ischemic insult (T2VO). Methods Age-matched senescence-resistant inbred strain mice (SAMR1) were used as control. SAMP8 received T2VO (T2VO-SAMP8) or sham operation (sham-SAMP8) at day 0. These SAMP8 groups were administered CTS (750 mg/kg, p.o.) or water daily for three weeks from day 3. Results Compared with the control group, both sham-SAMP8 and T2VO-SAMP8 groups exhibited cognitive deficits in the object discrimination and water maze tests and emotional abnormality in the elevated plus maze test. T2VO significantly exacerbated spatial cognitive deficits of SAMP8 elucidated by the water maze test. CTS administration ameliorated the cognitive deficits and emotional abnormality of sham- and T2VO-SAMP8 groups. Western blotting and immunohistochemical studies revealed a marked decrease in the levels of phosphorylated forms of neuroplasticity-related proteins, N-methyl-D-aspartate receptor 1 (NMDAR1), Ca2+/calmodulin-dependent protein kinase II (CaMKII), cyclic AMP responsive element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in the frontal cortices of sham-SAMP8 and T2VO-SAMP8. Moreover, these animal groups showed significantly reduced levels of vasculogenesis/angiogenesis factors, vascular endothelial growth factor (VEGF), VEGF receptor type 2 (VEGFR2), platelet-derived growth factor-A (PDGF-A) and PDGF receptor α (PDGFRα). CTS treatment reversed the expression levels of these factors down-regulated in the brains of sham- and T2VO-SAMP8. Conclusion Recovery of impaired neuroplasticity system and VEGF/PDGF systems may play a role in the ameliorative effects of CTS on cognitive dysfunction caused by aging and ischemic insult. PMID:21943225

Virtual Environmental Enrichment through Video Games Improves Hippocampal-Associated Memory

PubMed Central

Clemenson, Gregory D.

2015-01-01

The positive effects of environmental enrichment and their neural bases have been studied extensively in the rodent (van Praag et al., 2000). For example, simply modifying an animal's living environment to promote sensory stimulation can lead to (but is not limited to) enhancements in hippocampal cognition and neuroplasticity and can alleviate hippocampal cognitive deficits associated with neurodegenerative diseases and aging. We are interested in whether these manipulations that successfully enhance cognition (or mitigate cognitive decline) have similar influences on humans. Although there are many “enriching” aspects to daily life, we are constantly adapting to new experiences and situations within our own environment on a daily basis. Here, we hypothesize that the exploration of the vast and visually stimulating virtual environments within video games is a human correlate of environmental enrichment. We show that video gamers who specifically favor complex 3D video games performed better on a demanding recognition memory task that assesses participants' ability to discriminate highly similar lure items from repeated items. In addition, after 2 weeks of training on the 3D video game Super Mario 3D World, naive video gamers showed improved mnemonic discrimination ability and improvements on a virtual water maze task. Two control conditions (passive and training in a 2D game, Angry Birds), showed no such improvements. Furthermore, individual performance in both hippocampal-associated behaviors correlated with performance in Super Mario but not Angry Birds, suggesting that how individuals explored the virtual environment may influence hippocampal behavior. SIGNIFICANCE STATEMENT The hippocampus has long been associated with episodic memory and is commonly thought to rely on neuroplasticity to adapt to the ever-changing environment. In animals, it is well understood that exposing animals to a more stimulating environment, known as environmental enrichment, can stimulate neuroplasticity and improve hippocampal function and performance on hippocampally mediated memory tasks. Here, we suggest that the exploration of vast and visually stimulating environments within modern-day video games can act as a human correlate of environmental enrichment. Training naive video gamers in a rich 3D, but not 2D, video game, resulted in a significant improvement in hippocampus-associated cognition using several behavioral measures. Our results suggest that modern day video games may provide meaningful stimulation to the human hippocampus. PMID:26658864

Virtual Environmental Enrichment through Video Games Improves Hippocampal-Associated Memory.

PubMed

Clemenson, Gregory D; Stark, Craig E L

2015-12-09

The positive effects of environmental enrichment and their neural bases have been studied extensively in the rodent (van Praag et al., 2000). For example, simply modifying an animal's living environment to promote sensory stimulation can lead to (but is not limited to) enhancements in hippocampal cognition and neuroplasticity and can alleviate hippocampal cognitive deficits associated with neurodegenerative diseases and aging. We are interested in whether these manipulations that successfully enhance cognition (or mitigate cognitive decline) have similar influences on humans. Although there are many "enriching" aspects to daily life, we are constantly adapting to new experiences and situations within our own environment on a daily basis. Here, we hypothesize that the exploration of the vast and visually stimulating virtual environments within video games is a human correlate of environmental enrichment. We show that video gamers who specifically favor complex 3D video games performed better on a demanding recognition memory task that assesses participants' ability to discriminate highly similar lure items from repeated items. In addition, after 2 weeks of training on the 3D video game Super Mario 3D World, naive video gamers showed improved mnemonic discrimination ability and improvements on a virtual water maze task. Two control conditions (passive and training in a 2D game, Angry Birds), showed no such improvements. Furthermore, individual performance in both hippocampal-associated behaviors correlated with performance in Super Mario but not Angry Birds, suggesting that how individuals explored the virtual environment may influence hippocampal behavior. The hippocampus has long been associated with episodic memory and is commonly thought to rely on neuroplasticity to adapt to the ever-changing environment. In animals, it is well understood that exposing animals to a more stimulating environment, known as environmental enrichment, can stimulate neuroplasticity and improve hippocampal function and performance on hippocampally mediated memory tasks. Here, we suggest that the exploration of vast and visually stimulating environments within modern-day video games can act as a human correlate of environmental enrichment. Training naive video gamers in a rich 3D, but not 2D, video game, resulted in a significant improvement in hippocampus-associated cognition using several behavioral measures. Our results suggest that modern day video games may provide meaningful stimulation to the human hippocampus. Copyright © 2015 the authors 0270-6474/15/3516116-10$15.00/0.

Factors Affecting Volume Changes of the Somatosensory Cortex in Patients with Spinal Cord Injury: To Be Considered for Future Neuroprosthetic Design.

PubMed

Höller, Yvonne; Tadzic, Arijan; Thomschewski, Aljoscha C; Höller, Peter; Leis, Stefan; Tomasi, Santino Ottavio; Hofer, Christoph; Bathke, Arne; Nardone, Raffaele; Trinka, Eugen

2017-01-01

Spinal cord injury (SCI) leads to severe chronic disability, but also to secondary adaptive changes upstream to the injury in the brain which are most likely induced due to the lack of afferent information. These neuroplastic changes are a potential target for innovative therapies such as neuroprostheses, e.g., by stimulation in order to evoke sensation or in order to suppress phantom limb pain. Diverging results on gray matter atrophy have been reported in patients with SCI. Detectability of atrophy seems to depend on the selection of the regions of interest, while whole-brain approaches are not sensitive enough. In this study, we discussed previous research approaches and analyzed differential atrophic changes in incomplete SCI using manual segmentation of the somatosensory cortex. Patients with incomplete SCI (ASIA C-D), with cervical (N = 5) and thoracic (N = 6) injury were included. Time since injury was ≤12 months in 7 patients, and 144, 152, 216, and 312 months in the other patients. Age at the injury was ≤26 years in 4 patients and ≥50 years in 7 patients. A sample of 12 healthy controls was included in the study. In contrast to all previous studies that used voxel-based morphometry, we performed manual segmentation of the somatosensory cortex in the postcentral gyrus from structural magnetic resonance images and normalized the calculated volumes against the sum of volumes of an automated whole-head segmentation. Volumes were smaller in patients than in controls ( p  = 0.011), and as a tendency, female patients had smaller volumes than male patients ( p  = 0.017, uncorrected). No effects of duration (subacute vs. chronic), level of lesion (cervical vs. thoracic), region (left vs. right S1), and age at onset (≤26 vs. ≥50 years) was found. Our results demonstrate volume loss of S1 in incomplete SCI and encourage further research with larger sample sizes on volumetric changes in the acute and chronic stage of SCI, in order to document the moderating effect of type and location of injury on neuroplastic changes. A better understanding of neuroplastic changes in the sensorimotor cortex after SCI and its interaction with sex is needed in order to develop efficient rehabilitative interventions and neuroprosthetic technologies.

Functional deficits in carpal tunnel syndrome reflect reorganization of primary somatosensory cortex

PubMed Central

Kettner, Norman; Holden, Jameson; Lee, Jeungchan; Kim, Jieun; Cina, Stephen; Malatesta, Cristina; Gerber, Jessica; McManus, Claire; Im, Jaehyun; Libby, Alexandra; Mezzacappa, Pia; Morse, Leslie R.; Park, Kyungmo; Audette, Joseph; Tommerdahl, Mark; Napadow, Vitaly

2014-01-01

Carpal tunnel syndrome, a median nerve entrapment neuropathy, is characterized by sensorimotor deficits. Recent reports have shown that this syndrome is also characterized by functional and structural neuroplasticity in the primary somatosensory cortex of the brain. However, the linkage between this neuroplasticity and the functional deficits in carpal tunnel syndrome is unknown. Sixty-three subjects with carpal tunnel syndrome aged 20–60 years and 28 age- and sex-matched healthy control subjects were evaluated with event-related functional magnetic resonance imaging at 3 T while vibrotactile stimulation was delivered to median nerve innervated (second and third) and ulnar nerve innervated (fifth) digits. For each subject, the interdigit cortical separation distance for each digit’s contralateral primary somatosensory cortex representation was assessed. We also evaluated fine motor skill performance using a previously validated psychomotor performance test (maximum voluntary contraction and visuomotor pinch/release testing) and tactile discrimination capacity using a four-finger forced choice response test. These biobehavioural and clinical metrics were evaluated and correlated with the second/third interdigit cortical separation distance. Compared with healthy control subjects, subjects with carpal tunnel syndrome demonstrated reduced second/third interdigit cortical separation distance (P < 0.05) in contralateral primary somatosensory cortex, corroborating our previous preliminary multi-modal neuroimaging findings. For psychomotor performance testing, subjects with carpal tunnel syndrome demonstrated reduced maximum voluntary contraction pinch strength (P < 0.01) and a reduced number of pinch/release cycles per second (P < 0.05). Additionally, for four-finger forced-choice testing, subjects with carpal tunnel syndrome demonstrated greater response time (P < 0.05), and reduced sensory discrimination accuracy (P < 0.001) for median nerve, but not ulnar nerve, innervated digits. Moreover, the second/third interdigit cortical separation distance was negatively correlated with paraesthesia severity (r = −0.31, P < 0.05), and number of pinch/release cycles (r = −0.31, P < 0.05), and positively correlated with the second and third digit sensory discrimination accuracy (r = 0.50, P < 0.05). Therefore, reduced second/third interdigit cortical separation distance in contralateral primary somatosensory cortex was associated with worse symptomatology (particularly paraesthesia), reduced fine motor skill performance, and worse sensory discrimination accuracy for median nerve innervated digits. In conclusion, primary somatosensory cortex neuroplasticity for median nerve innervated digits in carpal tunnel syndrome is indeed maladaptive and underlies the functional deficits seen in these patients. PMID:24740988

G-protein mediates voltage regulation of agonist binding to muscarinic receptors: effects on receptor-Na/sup +/ channel interaction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cohen-Armon, M.; Garty, H.; Sokolovsky, M.

1988-01-12

The authors previous experiments in membranes prepared from rat heart and brain led them to suggest that the binding of agonist to the muscarinic receptors and to the Na/sup +/ channels is a coupled event mediated by guanine nucleotide binding protein(s) (G-protein(s)). These in vitro findings prompted us to employ synaptoneurosomes from brain stem tissue to examine (i) the binding properties of (/sup 3/H) acetylcholine at resting potential and under depolarization conditions in the absence and presence of pertussis toxin; (ii) the binding of (/sup 3/H)batrachotoxin to Na/sup +/ channel(s) in the presence of the muscarinic agonists; and (iii) muscarinicallymore » induced /sup 22/Na/sup +/ uptake in the presence and absence of tetrodotoxin, which blocks Na/sup +/ channels. The findings indicate that agonist binding to muscarinic receptors is voltage dependent, that this process is mediated by G-protein(s), and that muscarinic agonists induce opening of Na/sup +/channels. The latter process persists even after pertussis toxin treatment, indicating that it is not likely to be mediated by pertussis toxin sensitive G-protein(s). The system with its three interacting components-receptor, G-protein, and Na/sup +/ channel-is such that at resting potential the muscarinic receptor induces opening of Na/sup +/ channels; this property may provide a possible physiological mechanism for the depolarization stimulus necessary for autoexcitation or repetitive firing in heart or brain tissues.« less

EphA4 Activation of c-Abl Mediates Synaptic Loss and LTP Blockade Caused by Amyloid-β Oligomers

PubMed Central

M. Vargas, Lina; Leal, Nancy; Estrada, Lisbell D.; González, Adrian; Serrano, Felipe; Araya, Katherine; Gysling, Katia; Inestrosa, Nibaldo C.; Pasquale, Elena B.; Alvarez, Alejandra R.

2014-01-01

The early stages of Alzheimer's disease are characterised by impaired synaptic plasticity and synapse loss. Here, we show that amyloid-β oligomers (AβOs) activate the c-Abl kinase in dendritic spines of cultured hippocampal neurons and that c-Abl kinase activity is required for AβOs-induced synaptic loss. We also show that the EphA4 receptor tyrosine kinase is upstream of c-Abl activation by AβOs. EphA4 tyrosine phosphorylation (activation) is increased in cultured neurons and synaptoneurosomes exposed to AβOs, and in Alzheimer-transgenic mice brain. We do not detect c-Abl activation in EphA4-knockout neurons exposed to AβOs. More interestingly, we demonstrate EphA4/c-Abl activation is a key-signalling event that mediates the synaptic damage induced by AβOs. According to this results, the EphA4 antagonistic peptide KYL and c-Abl inhibitor STI prevented i) dendritic spine reduction, ii) the blocking of LTP induction and iii) neuronal apoptosis caused by AβOs. Moreover, EphA4-/- neurons or sh-EphA4-transfected neurons showed reduced synaptotoxicity by AβOs. Our results are consistent with EphA4 being a novel receptor that mediates synaptic damage induced by AβOs. EphA4/c-Abl signalling could be a relevant pathway involved in the early cognitive decline observed in Alzheimer's disease patients. PMID:24658113

Aniracetam improves behavioural responses and facilitates signal transduction in the rat brain.

PubMed

Ventra, C; Grimaldi, M; Meucci, O; Scorziello, A; Apicella, A; Filetti, E; Marino, A; Schettini, G

1994-01-01

The effect of aniracetam (10, 50, 100 mg/kg i.p. daily for 15 days) on both behavioural and biochemical parameters was investigated in the adult rat. Animals given aniracetam (50 mg/kg 1 h before the trial) showed a significant increase in the percentage of conditioned active avoidance responses and a reduction of latency times. Aniracetam significantly counteracted the scopolamine-induced memory failure at the passive avoidance (step down) test, while it did not modify the locomotion of the animals. In purified frontocortical and hippocampal synaptic membranes of rats treated with aniracetam (50 mg/kg i.p. daily for 15 days) a potentiation of basal, carbamylcholine-, dopamine- and norepinephrine-stimulated adenylyl cyclase activity was observed, while forskolin-stimulated enzyme activity was not modified. With regard to inositol phosphate production measured in fronto-cortical synaptoneurosomes, aniracetam potentiated the stimulation by angiotensin II, while the stimulation by carbamylcholine, not affected by 10 and 50 mg/kg aniracetam, was notably, although not significantly, decreased by 100 mg/kg aniracetam. Furthermore, in synaptosomes derived from hippocampus, aniracetam (50 mg/kg i.p. daily for 15 days) caused an increase of both basal and K(+)-stimulated intrasynaptosomal Ca(2+) concentration. In conclusion, a correlation between the improvement of behavioural performance and the modulation of transducing systems by aniracetam seems to take place in brain areas, such as frontal cortex and hippocampus, known to play a major role in the control of cognitive functions.

Transient decrease in nociceptor GRK2 expression produces long–term enhancement in inflammatory pain

PubMed Central

Ferrari, Luiz F.; Bogen, Oliver; Alessandri–Haber, Nicole; Levine, Emma; Gear, Robert W.; Levine, Jon D.

2012-01-01

In heterozygous mice, attenuation of G-protein-coupled receptor kinase 2 (GRK2) level in nociceptors is associated with enhanced and prolonged inflammatory hyperalgesia. To further elucidate the role of GRK2 in nociceptor function we reversibly decreased GRK2 expression using intrathecal antisense oligodeoxynucleotide (AS-ODN). GRK2 AS-ODN administration led to an enhanced and prolonged hyperalgesia induced by prostaglandin E 2, epinephrine and carrageenan. Morover, this effect persisted unattenuated 2 weeks after the last dose of antisense, well after GRK2 protein recovered, suggesting that transient attenuation of GRK2 produced neuroplastic changes in nociceptor function. Unlike hyperalgesic priming induced by transient attenuation of GRK2 produced neuroplastic changes in nociceptor function. Unlike hyperalgesic priming induced by transient activation of protein kinase C epsilon (PKCε), (Aley et al., 2000, Parada et al., 2003b), the enhanced and prolonged hyperalgesia following attenuation of GRK2 is PKCε- and cytoplasmic polyadenylation element binding protein (CPEB)-independent and is protein kinase A (PKA)- and Src tyrosine kinase (Src)-dependent. Finally, rats treated with GRK2 AS-ODN exhibited enhanced and prolonged hyperalgesia induced by direct activation of second messengers, adenyl cyclase, Epac or PKA, suggesting changes downstream of G-protein-coupled receptors. Because inflammation can produce a decrease in GRK2, such a mechanism could help explain a predilection to develop chronic pain, after resolution of acute inflammation. PMID:22796071

Benefits from Vergence Rehabilitation: Evidence for Improvement of Reading Saccades and Fixations.

PubMed

Daniel, François; Morize, Aurélien; Brémond-Gignac, Dominique; Kapoula, Zoï

2016-01-01

We hypothesize that binocular coordination of saccades is based on continuous neuroplasticity involving interactions of saccades and vergence. To test this hypothesis we study reading saccades in young students who were diagnosed for vergence disorders before and after vergence rehabilitation. Following orthoptic evaluation and symptomatology screening, 5 weekly sessions of vergence rehabilitation were applied with the REMOBI vergence double step protocole (see Kapoula et al., 2016). Using the Eyeseecam videoculography device we measured vergence as well as saccades and fixations during a reading test four times: at the beginning and at the end of the first and of the fifth vergence rehabilitation session. The results show elimination of symptoms, improvement of clinical orthoptic scores, and importantly increase of measured vergence gain and reduction of inter-trial variability. Improvement of the vergence was associated to a decrease of the disconjugacy of saccades during reading but also to shortening of fixation durations, to reduction of the number of regressive saccades and to a better correction of the intra-saccadic disconjugacy during the following fixation. The results corroborate the hypothesis of neuroplasticity based on saccade vergence interaction in young adults. It validates the clinical validity of the vergence double-step REMOBI method as a means to improve both, vergence and reading performances. It opens a new research approach on the link between fine binocular coordination of saccades, quality of the vergence response, attention, cognition and reading.

STEROID RECEPTOR COACTIVATOR 2 (SRC-2) MODULATES STEROID-DEPENDENT MALE SEXUAL BEHAVIOR AND NEUROPLASTICITY IN JAPANESE QUAIL (COTURNIX JAPONICA)

PubMed Central

Niessen, Neville-Andrew; Balthazart, Jacques; Ball, Gregory F.; Charlier, Thierry D.

2011-01-01

Steroid receptor coactivators are necessary for efficient transcriptional regulation by ligand-bound nuclear receptors, including estrogen and androgen receptors. SRC-2 modulates estrogen- and progesterone-dependent sexual behavior in female rats but its implication in the control of male sexual behavior has not been studied to our knowledge. We cloned and sequenced the complete quail SRC-2 transcript and showed by semi-quantitative PCR that SRC-2 expression is nearly ubiquitous, with high levels of expression in the kidney, cerebellum and diencephalon. Real time quantitative PCR did not reveal any differences between intact males and females the medial preoptic nucleus (POM), optic lobes and cerebellum. We next investigated the physiological and behavioral role of this coactivator using in vivo antisense oligonucleotide (AS) techniques. Daily injections in the third ventricle at the level of the POM of locked nucleic acid antisense targeting SRC-2 significantly reduced the expression of testosterone-dependent male-typical copulatory behavior but no inhibition of one aspect of the appetitive sexual behavior was observed. The volume of POM, defined by aromatase-immunoreactive cells, was markedly decreased in animals treated with AS as compared to controls. These results demonstrate that SRC-2 plays a prominent role in the control of steroid-dependent male sexual behavior and its associated neuroplasticity in Japanese quail. PMID:21854393

Neuroplasticity-based computerized cognitive remediation for geriatric depression.

PubMed

Morimoto, Sarah Shizuko; Wexler, Bruce E; Alexopoulos, George S

2012-12-01

This article describes a novel treatment model designed to target specific neurocognitive deficits in geriatric depression with neuroplasticity-based computerized cognitive remediation (NBCCR). The recent National Institute of Mental Health (NIMH) report "From Discovery to Cure" calls for studies focusing on mechanisms of treatment response with the goal of arriving at new interventions for those who do not respond to existing treatments. We describe the process that led to the identification of specific executive deficits and their underlying neurobiology, as well as the rationale for targeting these symptoms as a part of a strategy intended to improve both executive dysfunction and depression. We then propose a strategy for further research in this emerging area. Despite significant developments, conventional antidepressant treatments leave many older adults still depressed and suffering. Psychotherapy may be effective in some depressed elders, although a recent review concluded that none of the available treatment studies meets stringent criteria for efficacy in the acute treatment of geriatric depression. Appropriately developed and targeted NBCCR, has the potential to serve as a novel treatment intervention for geriatric depression. Pathophysiological changes associated with executive dysfunction may be an appropriate target for NBCCR. Examining both behavioral changes and indices of structural integrity and functional change of networks related to cognitive and emotional regulation may lead to a novel treatment and elucidate the role of specific cerebral networks in geriatric depression. Copyright © 2012 John Wiley & Sons, Ltd.

Adult Mouse DRG Explant and Dissociated Cell Models to Investigate Neuroplasticity and Responses to Environmental Insults Including Viral Infection.

PubMed

Fornaro, Michele; Sharthiya, Harsh; Tiwari, Vaibhav

2018-03-09

This protocol describes an ex vivo model of mouse-derived dorsal root ganglia (DRG) explant and in vitro DRG-derived co-culture of dissociated sensory neurons and glial satellite cells. These are useful and versatile models to investigate a variety of biological responses associated with physiological and pathological conditions of the peripheral nervous system (PNS) ranging from neuron-glial interaction, neuroplasticity, neuroinflammation, and viral infection. The usage of DRG explant is scientifically advantageous compared to simplistic single cells models for multiple reasons. For instance, as an organotypic culture, the DRG explant allows ex vivo transfer of an entire neuronal network including the extracellular microenvironment that play a significant role in all the neuronal and glial functions. Further, DRG explants can also be maintained ex vivo for several days and the culture conditions can be perturbed as desired. In addition, the harvested DRG can be further dissociated into an in vitro co-culture of primary sensory neurons and satellite glial cells to investigate neuronal-glial interaction, neuritogenesis, axonal cone interaction with the extracellular microenvironment, and more general, any aspect associated with the neuronal metabolism. Therefore, the DRG-explant system offers a great deal of flexibility to study a wide array of events related to biological, physiological, and pathological conditions in a cost-effective manner.

Using Neuroplasticity-Based Auditory Training to Improve Verbal Memory in Schizophrenia

PubMed Central

Fisher, Melissa; Holland, Christine; Merzenich, Michael M.; Vinogradov, Sophia

2009-01-01

Objective Impaired verbal memory in schizophrenia is a key rate-limiting factor for functional outcome, does not respond to currently available medications, and shows only modest improvement after conventional behavioral remediation. The authors investigated an innovative approach to the remediation of verbal memory in schizophrenia, based on principles derived from the basic neuroscience of learning-induced neuroplasticity. The authors report interim findings in this ongoing study. Method Fifty-five clinically stable schizophrenia subjects were randomly assigned to either 50 hours of computerized auditory training or a control condition using computer games. Those receiving auditory training engaged in daily computerized exercises that placed implicit, increasing demands on auditory perception through progressively more difficult auditory-verbal working memory and verbal learning tasks. Results Relative to the control group, subjects who received active training showed significant gains in global cognition, verbal working memory, and verbal learning and memory. They also showed reliable and significant improvement in auditory psychophysical performance; this improvement was significantly correlated with gains in verbal working memory and global cognition. Conclusions Intensive training in early auditory processes and auditory-verbal learning results in substantial gains in verbal cognitive processes relevant to psychosocial functioning in schizophrenia. These gains may be due to a training method that addresses the early perceptual impairments in the illness, that exploits intact mechanisms of repetitive practice in schizophrenia, and that uses an intensive, adaptive training approach. PMID:19448187

Relationship between brain plasticity, learning and foraging performance in honey bees.

PubMed

Cabirol, Amélie; Cope, Alex J; Barron, Andrew B; Devaud, Jean-Marc

2018-01-01

Brain structure and learning capacities both vary with experience, but the mechanistic link between them is unclear. Here, we investigated whether experience-dependent variability in learning performance can be explained by neuroplasticity in foraging honey bees. The mushroom bodies (MBs) are a brain center necessary for ambiguous olfactory learning tasks such as reversal learning. Using radio frequency identification technology, we assessed the effects of natural variation in foraging activity, and the age when first foraging, on both performance in reversal learning and on synaptic connectivity in the MBs. We found that reversal learning performance improved at foraging onset and could decline with greater foraging experience. If bees started foraging before the normal age, as a result of a stress applied to the colony, the decline in learning performance with foraging experience was more severe. Analyses of brain structure in the same bees showed that the total number of synaptic boutons at the MB input decreased when bees started foraging, and then increased with greater foraging intensity. At foraging onset MB structure is therefore optimized for bees to update learned information, but optimization of MB connectivity deteriorates with foraging effort. In a computational model of the MBs sparser coding of information at the MB input improved reversal learning performance. We propose, therefore, a plausible mechanistic relationship between experience, neuroplasticity, and cognitive performance in a natural and ecological context.

The impact of an anti-gravity treadmill (AlterG) training on walking capacity and corticospinal tract structure in children with cerebral palsy.

PubMed

Azizi, Sh; Marzbani, H; Raminfard, S; Birgani, P M; Rasooli, A H; Mirbagheri, M M

2017-07-01

We studied the effects of an anti-gravity treadmill (AlterG) training on walking capacity and corticospinal tract structure in children with Cerebral Palsy (CP). AlterG can help CP children walk on the treadmill by reducing their weights up to 80% and maintain their balance during locomotion. AlterG training thus has the potential to improve walking capacity permanently as it can provide systematic and intense locomotor training for sufficiently long period of time and produce brain neuroplasticity. AlterG training was given for 45 minutes, three times a week for two months. The neuroplasticity of corticospinal tract was evaluated using Diffusion Tensor Imaging (DTI). The fractional Anisotropy (FA) feature was extracted to quantify structural changes of the corticospinal tract. Walking capacity was evaluated using popular clinical measurements of gait; i.e., walking speed, mobility and balance. The evaluations were done before and after training. Our results revealed that AlterG training resulted in an increase in average FA value of the corticospinal tract following the training. The outcome measures of clinical assessments of gait presented enhanced walking capacity of the CP subjects. Our findings indicated that the improved walking capacity was concurrent with the enhancement of the corticospinal tract structure. The clinical implication is that AlterG training may be considered as a therapeutic tool for permanent gait improvement in CP children.

Changes of cortical excitability as markers of antidepressant response in bipolar depression: preliminary data obtained by combining transcranial magnetic stimulation (TMS) and electroencephalography (EEG).

PubMed

Canali, Paola; Sferrazza Papa, Giovanna; Casali, Adenauer G; Schiena, Giandomenico; Fecchio, Matteo; Pigorini, Andrea; Smeraldi, Enrico; Colombo, Cristina; Benedetti, Francesco

2014-12-01

It is still unclear which biological changes are needed to recover from a major depressive episode. Current perspectives focus on cortical synaptic neuroplasticity. Measures of cortical responses evoked by transcranial magnetic stimulation (TMS) change with sleep homeostasic pressure in humans and approximate measures of synaptic strength in animal models. Using repeated total sleep deprivation as a model of antidepressant treatment, we aimed to correlate recovery from depression with these measures of cortical excitability. We recorded electroencephalographic responses to TMS in the prefrontal cortex of 21 depressed inpatients with bipolar disorder treated with repeated sleep deprivation combined with light therapy. We performed seven TMS/electroencephalography sessions during one week and calculated three measures of cortical excitability. Cortical excitability progressively increased during the antidepressant treatment and as a function of time awake. Higher values differentiated responders from non-responders at baseline and during and after treatment on all measures. Changes in measures of cortical excitability parallel and predict antidepressant response to combined sleep deprivation and light therapy. Data suggest that promoting cortical plasticity in bipolar depression could be a major effect of successful antidepressant treatments, and that patients not responding could suffer a persistent impairment in their neuroplasticity mechanisms. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Opioid receptor-mediated hyperalgesia and antinociceptive tolerance induced by sustained opiate delivery.

PubMed

Gardell, Luis R; King, Tamara; Ossipov, Michael H; Rice, Kenner C; Lai, Josephine; Vanderah, Todd W; Porreca, Frank

2006-03-20

Opiates are commonly used to treat moderate to severe pain and can be used over prolonged periods in states of chronic pain such as those associated with cancer. In addition, to analgesic actions, studies show that opiate administration can paradoxically induce hyperalgesia. At the pre-clinical level, such hyperalgesia is associated with numerous pronociceptive neuroplastic changes within the primary afferent fibers and the spinal cord. In rodents, sustained opiate administration also induces antinociceptive tolerance. The mechanisms by which prolonged opiate exposure induces hyperalgesia and the relationship of this state to antinociceptive tolerance remain unclear. The present study was aimed at determining whether sustained opiate-induced hyperalgesia, associated neuroplasticity and antinociceptive tolerance are the result of specific opiate interaction at opiate receptors. Enantiomers of oxymorphone, a mu opioid receptor agonist, were administered to rats by spinal infusion across 7 days. Sustained spinal administration of (-)-oxymorphone, but not its inactive enantiomer (+)-oxymorphone or vehicle, upregulated spinal dynorphin content, produced thermal and tactile hypersensitivity, and produced antinociceptive tolerance. These results indicate that these pronociceptive actions of sustained opiate administration require specific interaction with opiate receptors and are unlikely to be the result of accumulation of potentially excitatory metabolic products. While the precise mechanisms, which may account for these pronociceptive changes remain to be unraveled, the present data point to plasticity initiated by opiate receptor interaction.

Decreased Hippocampal Neuroplasticity and Behavioral Impairment in an Animal Model of Inhalant Abuse

PubMed Central

Malloul, Hanaa; Bennis, Mohammed; Bonzano, Sara; Gambarotta, Giovanna; Perroteau, Isabelle; De Marchis, Silvia; Ba-M'hamed, Saadia

2018-01-01

Thinners are highly toxic chemicals widely employed as organic solvents in industrial and domestic use. They have psychoactive properties when inhaled, and their chronic abuse as inhalants is associated with severe long-term health effects, including brain damage and cognitive-behavioral alterations. Yet, the sites and mechanisms of action of these compounds on the brain are far from being fully understood. Here, we investigated the consequences of paint thinner inhalation in adult male mice. Depression-like behaviors and an anxiolytic effect were found following repeated exposure in chronic treatments lasting 12 weeks. Both subchronic (6 weeks) and chronic treatments impaired learning and memory functions, while no changes were observed after acute treatment. To investigate possible molecular/structural alterations underlying such behavioral changes, we focused on the hippocampus. Notably, prolonged, but not acute thinner inhalation strongly affected adult neurogenesis in the dentate gyrus (DG), reducing progenitor cell proliferation after chronic treatments and impairing the survival of newborn neurons following both chronic and subchronic treatments. Furthermore, a down-regulation in the expression of BDNF and NMDA receptor subunits as well as a reduction in CREB expression/phosphorylation were found in the hippocampi of chronically treated mice. Our findings demonstrate for the first time significant structural and molecular changes in the adult hippocampus after prolonged paint thinner inhalation, indicating reduced hippocampal neuroplasticity and strongly supporting its implication in the behavioral dysfunctions associated to inhalant abuse. PMID:29472835

Long-term effects of spinal cord injury on sexual function in men: implications for neuroplasticity.

PubMed

Anderson, K D; Borisoff, J F; Johnson, R D; Stiens, S A; Elliott, S L

2007-05-01

Secure, web-based survey. Elicit specific information about sexual function from men with spinal cord injuries (SCI). World-wide web. Individuals 18 years or older living with SCI obtained a pass-code to enter a secure website and then answered survey questions. The presence of genital sensation was positively correlated with the ability to feel a build up of sexual tension in the body during sexual stimulation and in the feeling that mental arousal translates to the genitals as physical sensation. There was an inverse relationship between developing new areas of arousal above the level of lesion and not having sensation or movement below the lesion. A positive relationship existed between the occurrence of spasticity during sexual activity and erectile ability. Roughly 60% of the subjects had tried some type of erection enhancing method. Only 48% had successfully achieved ejaculation postinjury and the most commonly used methods were hand stimulation, sexual intercourse, and vibrostimulation. The most commonly cited reasons for trying to ejaculate were for pleasure and for sexual intimacy. Less than half reported having experienced orgasm postinjury and this was influenced by the length of time postinjury and sacral sparing. SCI not only impairs male erectile function and ejaculatory ability, but also alters sexual arousal in a manner suggestive of neuroplasticity. More research needs to be pursued in a manner encompassing all aspects of sexual function.

Repeated intravenous doxapram induces phrenic motor facilitation

PubMed Central

Sandhu, MS; Lee, KZ; Gonzalez-Rothi, EJ; Fuller, DD

2013-01-01

Doxapram is a respiratory stimulant used to treat hypoventilation. Here we investigated whether doxapram could also trigger respiratory neuroplasticity. Specifically, we hypothesized that intermittent delivery of doxapram at low doses would lead to long-lasting increases (i.e., facilitation) of phrenic motor output in anesthetized, vagotomized, and mechanically-ventilated rats. Doxapram was delivered intravenously in a single bolus (2 or 6 mg/kg) or as a series of 3 injections (2 mg/kg) at 5 min intervals. Control groups received pH-matched saline injections (vehicle) or no treatment (anesthesia time control). Doxapram evoked an immediate increase in phrenic output in all groups, but a persistent increase in burst amplitude only occurred after repeated dosing with 2 mg/kg. At 60 min following the last injection, phrenic burst amplitude was 168±24% of baseline (%BL) in the group receiving 3 injections (P < 0.05 vs. controls), but was 103±8%BL and 112±4%BL in the groups receiving a single dose of 2 or 6 mg/kg, respectively. Following bilateral section of the carotid sinus nerves, the acute phrenic response to doxapram (2 mg/kg) was reduced by 68% suggesting that at low doses the drug was acting primarily via the carotid chemoreceptors. We conclude that intermittent application of doxapram can trigger phrenic neuroplasticity, and this approach might be of use in the context of respiratory rehabilitation following neurologic injury. PMID:24013015

Robotic Mirror Therapy System for Functional Recovery of Hemiplegic Arms.

PubMed

Beom, Jaewon; Koh, Sukgyu; Nam, Hyung Seok; Kim, Wonshik; Kim, Yoonjae; Seo, Han Gil; Oh, Byung-Mo; Chung, Sun Gun; Kim, Sungwan

2016-08-15

Mirror therapy has been performed as effective occupational therapy in a clinical setting for functional recovery of a hemiplegic arm after stroke. It is conducted by eliciting an illusion through use of a mirror as if the hemiplegic arm is moving in real-time while moving the healthy arm. It can facilitate brain neuroplasticity through activation of the sensorimotor cortex. However, conventional mirror therapy has a critical limitation in that the hemiplegic arm is not actually moving. Thus, we developed a real-time 2-axis mirror robot system as a simple add-on module for conventional mirror therapy using a closed feedback mechanism, which enables real-time movement of the hemiplegic arm. We used 3 Attitude and Heading Reference System sensors, 2 brushless DC motors for elbow and wrist joints, and exoskeletal frames. In a feasibility study on 6 healthy subjects, robotic mirror therapy was safe and feasible. We further selected tasks useful for activities of daily living training through feedback from rehabilitation doctors. A chronic stroke patient showed improvement in the Fugl-Meyer assessment scale and elbow flexor spasticity after a 2-week application of the mirror robot system. Robotic mirror therapy may enhance proprioceptive input to the sensory cortex, which is considered to be important in neuroplasticity and functional recovery of hemiplegic arms. The mirror robot system presented herein can be easily developed and utilized effectively to advance occupational therapy.

Delayed plastic responses to anodal tDCS in older adults

PubMed Central

Fujiyama, Hakuei; Hyde, Jane; Hinder, Mark R.; Kim, Seok-Jin; McCormack, Graeme H.; Vickers, James C.; Summers, Jeffery J.

2014-01-01

Despite the abundance of research reporting the neurophysiological and behavioral effects of transcranial direct current stimulation (tDCS) in healthy young adults and clinical populations, the extent of potential neuroplastic changes induced by tDCS in healthy older adults is not well understood. The present study compared the extent and time course of anodal tDCS-induced plastic changes in primary motor cortex (M1) in young and older adults. Furthermore, as it has been suggested that neuroplasticity and associated learning depends on the brain-derived neurotrophic factor (BDNF) gene polymorphisms, we also assessed the impact of BDNF polymorphism on these effects. Corticospinal excitability was examined using transcranial magnetic stimulation before and following (0, 10, 20, 30 min) anodal tDCS (30 min, 1 mA) or sham in young and older adults. While the overall extent of increases in corticospinal excitability induced by anodal tDCS did not vary reliably between young and older adults, older adults exhibited a delayed response; the largest increase in corticospinal excitability occurred 30 min following stimulation for older adults, but immediately post-stimulation for the young group. BDNF genotype did not result in significant differences in the observed excitability increases for either age group. The present study suggests that tDCS-induced plastic changes are delayed as a result of healthy aging, but that the overall efficacy of the plasticity mechanism remains unaffected. PMID:24936185

The Effects of Aerobic Exercise on the Recovery of Walking Ability and Neuroplasticity in People with Multiple Sclerosis: A Systematic Review of Animal and Clinical Studies

PubMed Central

2017-01-01

Introduction Walking is of high priority for people with multiple sclerosis (PwMS). It remains unclear whether aerobic exercise can improve walking ability and upregulate neurotrophins. This review aims to consolidate evidence to develop optimal aerobic training parameters to enhance walking outcomes and neuroplasticity in PwMS. Methods Clinical studies examining aerobic exercise for ≥3 weeks, having outcomes on walking with or without neurotrophic markers, were included. Studies utilizing animal models of MS were included if they employed aerobic exercise with outcomes on neurological recovery and neurotrophins. From a total of 1783 articles, 12 clinical and 5 animal studies were included. Results Eleven clinical studies reported improvements in walking ability. Only two clinical studies evaluated both walking and neurotrophins, and neither found an increase in neurotrophins despite improvements in walking. Patients with significant walking impairments were underrepresented. Long-term follow-up revealed mixed results. Two animal studies reported a positive change in both neurological recovery and neurotrophins. Conclusion Aerobic exercise improves walking ability in PwMS. Gains are not consistently maintained at 2- to 9-month follow-up. Studies examining levels of neurotrophins are inconclusive, necessitating further research. Aerobic exercise enhances both neurological recovery and neurotrophins in animal studies when started 2 weeks before induction of MS. PMID:29181199

Coordinated dysregulation of mRNAs and microRNAs in the rat medial prefrontal cortex following a history of alcohol dependence

PubMed Central

Tapocik, Jenica D.; Solomon, Matthew; Flanigan, Meghan; Meinhardt, Marcus; Barbier, Estelle; Schank, Jesse; Schwandt, Melanie; Sommer, Wolfgang H.; Heilig, Markus

2012-01-01

Long-term changes in brain gene expression have been identified in alcohol dependence, but underlying mechanisms remain unknown. Here, we examined the potential role of microRNAs for persistent gene expression changes in the rat medial prefrontal cortex after a history of alcohol dependence. Two-bottle free-choice alcohol consumption increased following 7-week exposure to intermittent alcohol intoxication. A bioinformatic approach using microarray analysis, qPCR, bioinformatic analysis, and microRNA-mRNA integrative analysis identified expression patterns indicative of a disruption in synaptic processes and neuroplasticity. 41 rat-microRNAs and 165 mRNAs in the medial prefrontal cortex were significantly altered after chronic alcohol exposure. A subset of the microRNAs and mRNAs was confirmed by qPCR. Gene ontology categories of differential expression pointed to functional processes commonly associated with neurotransmission, neuroadaptation, and synaptic plasticity. microRNA-mRNA expression pairing identified 33 microRNAs putatively targeting 89 mRNAs suggesting transcriptional networks involved in axonal guidance and neurotransmitter signaling. Our results demonstrate a significant shift in microRNA expression patterns in the medial prefrontal cortex following a history of dependence. Due to their global regulation of multiple downstream target transcripts, microRNAs may play a pivotal role in the reorganization of synaptic connections and long term neuroadaptations in alcohol dependence. microRNA-mediated alterations of transcriptional networks may be involved in disrupted prefrontal control over alcohol-drinking observed in alcoholic patients. PMID:22614244

Dichotomy and perceptual distortions in absolute pitch ability

PubMed Central

Athos, E. Alexandra; Levinson, Barbara; Kistler, Amy; Zemansky, Jason; Bostrom, Alan; Freimer, Nelson; Gitschier, Jane

2007-01-01

Absolute pitch (AP) is the rare ability to identify the pitch of a tone without the aid of a reference tone. Understanding both the nature and genesis of AP can provide insights into neuroplasticity in the auditory system. We explored factors that may influence the accuracy of pitch perception in AP subjects both during the development of the trait and in later age. We used a Web-based survey and a pitch-labeling test to collect perceptual data from 2,213 individuals, 981 (44%) of whom proved to have extraordinary pitch-naming ability. The bimodal distribution in pitch-naming ability signifies AP as a distinct perceptual trait, with possible implications for its genetic basis. The wealth of these data has allowed us to uncover unsuspected note-naming irregularities suggestive of a “perceptual magnet” centered at the note “A.” In addition, we document a gradual decline in pitch-naming accuracy with age, characterized by a perceptual shift in the “sharp” direction. These findings speak both to the process of acquisition of AP and to its stability. PMID:17724340

Neuroimaging and Recovery of Language in Aphasia

PubMed Central

Thompson, Cynthia K.; den Ouden, Dirk-Bart

2010-01-01

The use of functional neuroimaging techniques has advanced what is known about the neural mechanisms used to support language processing in aphasia resulting from brain damage. This paper highlights recent findings derived from neuroimaging studies focused on neuroplasticity of language networks, the role of the left and right hemispheres in this process, and studies examining how treatment affects the neurobiology of recovery. We point out variability across studies as well as factors related to this variability, and we emphasize challenges that remain for research. PMID:18957184

Pharmacological and Behavioral Enhancement of Neuroplasticity in the MPTP Lesioned Mouse and Nonhuman Primate

DTIC Science & Technology

2007-05-01

and post - synaptic dopamine biosynthesis, uptake and receptor expression as well as glutamatergic synapses. This hypothesis will be tested through...0.05) compared to mice at 7 days (9.6 ± 3.2%) or 30 days post -MPTP (16.5 ± 7.3%). The tail suspension test showed a significant increase in percent of...were compared using one-way analysis of variance (ANOVA), followed by the Fisher post hoc test for comparison of multiple means for the following

A Randomized Clinical Trial of Cognitive Enhancement Therapy for Adults with Autism Spectrum Disorders

DTIC Science & Technology

2015-10-01

This project is focused on conducting the first randomized-controlled trial of Cognitive Enhancement Therapy (CET) in 54 verbal adults with autism ...of the neuroplastic effects of CET on brain function in support of cognitive enhancement in adult autism . Analyses of treatment effects to date...the need and potential for CET to be a significant treatment advance for verbal adults with autism . Importantly, improvements were found in daily life function and in brain circuitry supporting core abilities.

Pharmacological and Behavioral Enhancement of Neuroplasticity in the MPTP-Lesioned Mouse and Nonhuman Primate

DTIC Science & Technology

2009-05-01

neurabin co-localization with eGFP. Figure 2. Neurabin Knock Down In Vitro: 293T cells were employed to test the effect of eGFP+shRNAmir 73 FUGW-VSVG...adults: a review of health benefits and the effectiveness of interventions. J Sports Sci 2004; 22 :703-25. 7. Gibbons RJ, Balady GJ, Bricker JT, et al...neurons (MSN) of the striatum, dictating the electrophysiological properties of these cells . 22 , 23 There is compelling data that the loss of nigral

Neural mechanisms of behavioral change in young adults with high-functioning autism receiving virtual reality social cognition training: A pilot study.

PubMed

Yang, Y J Daniel; Allen, Tandra; Abdullahi, Sebiha M; Pelphrey, Kevin A; Volkmar, Fred R; Chapman, Sandra B

2018-05-01

Measuring treatment efficacy in individuals with Autism Spectrum Disorder (ASD) relies primarily on behaviors, with limited evidence as to the neural mechanisms underlying these behavioral gains. This pilot study addresses this void by investigating neural and behavioral changes in a Phase I trial in young adults with high-functioning ASD who received an evidence-based behavioral intervention, Virtual Reality-Social Cognition Training over 5 weeks for a total of 10 hr. The participants were tested pre- and post-training with a validated biological/social versus scrambled/nonsocial motion neuroimaging task, previously shown to activate regions within the social brain networks. Three significant brain-behavior changes were identified. First, the right posterior superior temporal sulcus, a hub for socio-cognitive processing, showed increased brain activation to social versus nonsocial stimuli in individuals with greater gains on a theory-of-mind measure. Second, the left inferior frontal gyrus, a region for socio-emotional processing, tracked individual gains in emotion recognition with decreased activation to social versus nonsocial stimuli. Finally, the left superior parietal lobule, a region for visual attention, showed significantly decreased activation to nonsocial versus social stimuli across all participants, where heightened attention to nonsocial contingencies has been considered a disabling aspect of ASD. This study provides, albeit preliminary, some of the first evidence of the harnessable neuroplasticity in adults with ASD through an age-appropriate intervention in brain regions tightly linked to social abilities. This pilot trial motivates future efforts to develop and test social interventions to improve behaviors and supporting brain networks in adults with ASD. Autism Res 2018, 11: 713-725. © 2018 The Authors Autism Research published by International Society for Autism Research and Wiley Periodicals, Inc. This study addresses how the behavioral changes after treatment for ASD reflect underlying brain changes. Before and after receiving VR-SCT, young adults with high-functioning ASD passively viewed biological motion stimuli in a MRI scanner, tapping changes in the social brain network. The results reveal neuroplasticity in this age population, extending the window of opportunity for interventions to impact social competency in adults with ASD. © 2018 The Authors Autism Research published by International Society for Autism Research and Wiley Periodicals, Inc.

Spaceflight Effects on Neurocognitive Performance: Extent, Longevity and Neural Bases

NASA Technical Reports Server (NTRS)

Seidler, R. D.; Mulavara, A. P.; Koppelmans, V.; Kofman, I. S.; Cassady, K.; Yuan, P.; De Dios, Y. E.; Gadd, N.; Riascos, R. F.; Wood, S. J.;

Dauer-specific dendrite arborization in C. elegans is regulated by KPC-1/Furin.

PubMed

Schroeder, Nathan E; Androwski, Rebecca J; Rashid, Alina; Lee, Harksun; Lee, Junho; Barr, Maureen M

2013-08-19

Dendrites often display remarkably complex and diverse morphologies that are influenced by developmental and environmental cues. Neuroplasticity in response to adverse environmental conditions entails both hypertrophy and resorption of dendrites. How dendrites rapidly alter morphology in response to unfavorable environmental conditions is unclear. The nematode Caenorhabditis elegans enters into a stress-resistant dauer larval stage in response to an adverse environment. Here we show that the IL2 bipolar sensory neurons undergo dendrite arborization and axon remodeling during dauer development. When dauer larvae are returned to favorable environmental conditions, animals resume reproductive development and IL2 dendritic branches retract, leaving behind remnant branches in postdauer L4 and adult animals. The C. elegans furin homolog KPC-1 is required for dauer IL2 dendritic arborization and dauer-specific nictation behavior. KPC-1 is also necessary for dendritic arborization of PVD and FLP sensory neurons. In mammals, furin is essential, ubiquitously expressed, and associated with numerous pathologies, including neurodegenerative diseases. While broadly expressed in C. elegans neurons and epithelia, KPC-1 acts cell autonomously in IL2 neurons to regulate dauer-specific dendritic arborization and nictation. Neuroplasticity of the C. elegans IL2 sensory neurons provides a paradigm to study stress-induced and reversible dendritic branching, and the role of environmental and developmental cues in this process. The newly discovered role of KPC-1 in dendrite morphogenesis provides insight into the function of proprotein convertases in nervous system development. Copyright © 2013 Elsevier Ltd. All rights reserved.

Bone marrow stromal cells promote neuroplasticity of cerebral ischemic rats via a phosphorylated CRMP2-mediated mechanism.

PubMed

He, Xiang; Jiang, Ling; Dan, Qi-Qin; Lv, Qiang; Hu, Yue; Liu, Jia; Wang, Shu-Fen; Wang, Ting-Hua

2017-03-01

Collapsin response mediator protein 2 (CRMP2), an important protein involved in axonal growth and the maintenance of neuronal membrane integrity, has proved to be altered in nervous system diseases. This study was aimed to investigate the role of CRMP2 in bone marrow stromal cells (BMSCs) treating rats with cerebral ischemia. BMSCs were isolated from shaft of the femurs, tibiae, and humeri and were intra-carotid administrated immediately after middle cerebral artery occlusion (MCAO). Modified Neurological Severity Scores (mNSS) was conducted at 3, 7, 14dpo and the electrophysiologic evaluation was evaluated at 14dpo. Then all rats were sacrificed and brain tissues were harvested for RT-PCR, Western blot and Immunohistochemistry analysis. We found BMSCs treatment significantly improved the neurobehavioral performance impaired by ischemic brain injury, accompanied with the notably increasing levels of Synaptophysin (SYP) and Growth associated protein 43 (GAP43). We also found the protein level of phosphorylated CRMP2 (p-CRMP2) and phosphorylation-mediated protein including Glycogen synthase kinase 3 Beta (GSK3β), Cyclin-dependent kinase 5 (CDK5) were dramatically downregulated in ischemic rats following BMSCs transplant. Furthermore, the GSK3β-mediated factors including neurotrophic and signaling factors were all significantly upregulated in BMSCs-treated group. On the basis of these findings, we suggest that the neuroplasticity effect of BMSCs on cerebral ischemia may be associated with the phosphorylated modulation of CRMP2. Copyright © 2016 Elsevier B.V. All rights reserved.

Supplementation with complex milk lipids during brain development promotes neuroplasticity without altering myelination or vascular density

PubMed Central

Guillermo, Rosamond B.; Yang, Panzao; Vickers, Mark H.; McJarrow, Paul; Guan, Jian

2015-01-01

Background Supplementation with complex milk lipids (CML) during postnatal brain development has been shown to improve spatial reference learning in rats. Objective The current study examined histo-biological changes in the brain following CML supplementation and their relationship to the observed improvements in memory. Design The study used the brain tissues from the rats (male Wistar, 80 days of age) after supplementing with either CML or vehicle during postnatal day 10–80. Immunohistochemical staining of synaptophysin, glutamate receptor-1, myelin basic protein, isolectin B-4, and glial fibrillary acidic protein was performed. The average area and the density of the staining and the numbers of astrocytes and capillaries were assessed and analysed. Results Compared with control rats, CML supplementation increased the average area of synaptophysin staining and the number of GFAP astrocytes in the CA3 sub-region of the hippocampus (p<0.01), but not in the CA4 sub-region. The supplementation also led to an increase in dopamine output in the striatum that was related to nigral dopamine expression (p<0.05), but did not alter glutamate receptors, myelination or vascular density. Conclusion CML supplementation may enhance neuroplasticity in the CA3 sub-regions of the hippocampus. The brain regions-specific increase of astrocyte may indicate a supporting role for GFAP in synaptic plasticity. CML supplementation did not associate with postnatal white matter development or vascular remodelling. PMID:25818888

Aerobic Exercise as a Tool to Improve Hippocampal Plasticity and Function in Humans: Practical Implications for Mental Health Treatment

PubMed Central

Kandola, Aaron; Hendrikse, Joshua; Lucassen, Paul J.; Yücel, Murat

2016-01-01

Aerobic exercise (AE) has been widely praised for its potential benefits to cognition and overall brain and mental health. In particular, AE has a potent impact on promoting the function of the hippocampus and stimulating neuroplasticity. As the evidence-base rapidly builds, and given most of the supporting work can be readily translated from animal models to humans, the potential for AE to be applied as a therapeutic or adjunctive intervention for a range of human conditions appears ever more promising. Notably, many psychiatric and neurological disorders have been associated with hippocampal dysfunction, which may underlie the expression of certain symptoms common to these disorders, including (aspects of) cognitive dysfunction. Augmenting existing treatment approaches using AE based interventions may promote hippocampal function and alleviate cognitive deficits in various psychiatric disorders that currently remain untreated. Incorporating non-pharmacological interventions into clinical treatment may also have a number of other benefits to patient well being, such as limiting the risk of adverse side effects. This review incorporates both animal and human literature to comprehensively detail how AE is associated with cognitive enhancements and stimulates a cascade of neuroplastic mechanisms that support improvements in hippocampal functioning. Using the examples of schizophrenia and major depressive disorder, the utility and implementation of an AE intervention to the clinical domain will be proposed, aimed to reduce cognitive deficits in these, and related disorders. PMID:27524962

Responses of neurogenesis and neuroplasticity related genes to elevated CO2 levels in the brain of three teleost species.

PubMed

Lai, Floriana; Fagernes, Cathrine E; Bernier, Nicholas J; Miller, Gabrielle M; Munday, Philip L; Jutfelt, Fredrik; Nilsson, Göran E

2017-08-01

The continuous increase of anthropogenic CO 2 in the atmosphere resulting in ocean acidification has been reported to affect brain function in some fishes. During adulthood, cell proliferation is fundamental for fish brain growth and for it to adapt in response to external stimuli, such as environmental changes. Here we report the first expression study of genes regulating neurogenesis and neuroplasticity in brains of three-spined stickleback ( Gasterosteus aculeatus ), cinnamon anemonefish ( Amphiprion melanopus ) and spiny damselfish ( Acanthochromis polyacanthus ) exposed to elevated CO 2 The mRNA expression levels of the neurogenic differentiation factor (NeuroD) and doublecortin (DCX) were upregulated in three-spined stickleback exposed to high-CO 2 compared with controls, while no changes were detected in the other species. The mRNA expression levels of the proliferating cell nuclear antigen (PCNA) and the brain-derived neurotrophic factor (BDNF) remained unaffected in the high-CO 2 exposed groups compared to the control in all three species. These results indicate a species-specific regulation of genes involved in neurogenesis in response to elevated ambient CO 2 levels. The higher expression of NeuroD and DCX mRNA transcripts in the brain of high-CO 2 -exposed three-spined stickleback, together with the lack of effects on mRNA levels in cinnamon anemonefish and spiny damselfish, indicate differences in coping mechanisms among fish in response to the predicted-future CO 2 level. © 2017 The Author(s).

n-3 fatty acids: role in neurogenesis and neuroplasticity.

PubMed

Crupi, R; Marino, A; Cuzzocrea, S

2013-01-01

Omega-3 polyunsaturated fatty acids (PUFA) are essential unsaturated fatty acids with a double bond (C=C) starting after the third carbon atom from the end of the carbon chain. They are important nutrients but, unfortunately, mammals cannot synthesize them, whereby they must be obtained from food sources or from supplements. Amongst nutritionally important polyunsaturated n-3 fatty acids, α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are highly concentrated in the brain and have anti-oxidative stress, anti-inflammatory and antiapoptotic effects. They are involved in many bodily processes and may reportedly lead to neuron protection in neurological diseases. aged or damaged neurons and in Alzheimer's disease. Their effect in cognitive and behavioral functions and in several neurological and psychiatric disorders has been also proven. The dentate gyrus (DG), a sub-region of hippocampus, is implicated in cognition and mood regulation. The hippocampus represents one of the two areas in the mammalian brain in which adult neurogenesis occurs. This process is associated with beneficial effects on cognition, mood and chronic pharmacological treatment. The exposure to n-3 fatty acids enhances adult hippocampal neurogenesis associated with cognitive and behavioral processes, promotes synaptic plasticity by increasing long-term potentiation and modulates synaptic protein expression to stimulate the dendritic arborization and new spines formation. On this basis we review the effect of n-3 fatty acids on adult hippocampal neurogenesis and neuroplasticity. Moreover their possible use as a new therapeutic approach for neurodegenerative diseases is pointed out.

Mechanisms of Action and Persistent Neuroplasticity by Drugs of Abuse.

PubMed

Korpi, Esa R; den Hollander, Bjørnar; Farooq, Usman; Vashchinkina, Elena; Rajkumar, Ramamoorthy; Nutt, David J; Hyytiä, Petri; Dawe, Gavin S

2015-10-01

Adaptation of the nervous system to different chemical and physiologic conditions is important for the homeostasis of brain processes and for learning and remembering appropriate responses to challenges. Although processes such as tolerance and dependence to various drugs of abuse have been known for a long time, it was recently discovered that even a single pharmacologically relevant dose of various drugs of abuse induces neuroplasticity in selected neuronal populations, such as the dopamine neurons of the ventral tegmental area, which persist long after the drug has been excreted. Prolonged (self-) administration of drugs induces gene expression, neurochemical, neurophysiological, and structural changes in many brain cell populations. These region-specific changes correlate with addiction, drug intake, and conditioned drugs effects, such as cue- or stress-induced reinstatement of drug seeking. In rodents, adolescent drug exposure often causes significantly more behavioral changes later in adulthood than a corresponding exposure in adults. Clinically the most impairing and devastating effects on the brain are produced by alcohol during fetal development. In adult recreational drug users or in medicated patients, it has been difficult to find persistent functional or behavioral changes, suggesting that heavy exposure to drugs of abuse is needed for neurotoxicity and for persistent emotional and cognitive alterations. This review describes recent advances in this important area of research, which harbors the aim of translating this knowledge to better treatments for addictions and related neuropsychiatric illnesses. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

The VGF-derived peptide TLQP-21 contributes to inflammatory and nerve injury-induced hypersensitivity.

PubMed

Fairbanks, Carolyn A; Peterson, Cristina D; Speltz, Rebecca H; Riedl, Maureen S; Kitto, Kelley F; Dykstra, Jaclyn A; Braun, Patrick D; Sadahiro, Masato; Salton, Stephen R; Vulchanova, Lucy

2014-07-01

VGF (nonacronymic) is a granin-like protein that is packaged and proteolytically processed within the regulated secretory pathway. VGF and peptides derived from its processing have been implicated in neuroplasticity associated with learning, memory, depression, and chronic pain. In sensory neurons, VGF is rapidly increased following peripheral nerve injury and inflammation. Several bioactive peptides generated from the C-terminus of VGF have pronociceptive spinal effects. The goal of the present study was to examine the spinal effects of the peptide TLQP-21 and determine whether it participates in spinal mechanisms of persistent pain. Application of exogenous TLQP-21 induced dose-dependent thermal hyperalgesia in the warm-water immersion tail-withdrawal test. This hyperalgesia was inhibited by a p38 mitogen-activated protein kinase inhibitor, as well as inhibitors of cyclooxygenase and lipoxygenase. We used immunoneutralization of TLQP-21 to determine the function of the endogenous peptide in mechanisms underlying persistent pain. In mice injected intradermally with complete Freund adjuvant, intrathecal treatment with anti-TLQP-21 immediately prior to or 5hours after induction of inflammation dose-dependently inhibited tactile hypersensitivity and thermal hyperalgesia. Intrathecal anti-TL21 administration also attenuated the development and maintenance of tactile hypersensitivity in the spared nerve injury model of neuropathic pain. These results provide evidence that endogenous TLQP-21 peptide contributes to the mechanisms of spinal neuroplasticity after inflammation and nerve injury. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Functional and Structural Neuroplasticity Induced by Short-Term Tactile Training Based on Braille Reading.

PubMed

Debowska, Weronika; Wolak, Tomasz; Nowicka, Anna; Kozak, Anna; Szwed, Marcin; Kossut, Malgorzata

2016-01-01

Neuroplastic changes induced by sensory learning have been recognized within the cortices of specific modalities as well as within higher ordered multimodal areas. The interplay between these areas is not fully understood, particularly in the case of somatosensory learning. Here we examined functional and structural changes induced by short-term tactile training based of Braille reading, a task that requires both significant tactile expertise and mapping of tactile input onto multimodal representations. Subjects with normal vision were trained for 3 weeks to read Braille exclusively by touch and scanned before and after training, while performing a same-different discrimination task on Braille characters and meaningless characters. Functional and diffusion-weighted magnetic resonance imaging sequences were used to assess resulting changes. The strongest training-induced effect was found in the primary somatosensory cortex (SI), where we observed bilateral augmentation in activity accompanied by an increase in fractional anisotropy (FA) within the contralateral SI. Increases of white matter fractional anisotropy were also observed in the secondary somatosensory area (SII) and the thalamus. Outside of somatosensory system, changes in both structure and function were found in i.e., the fusiform gyrus, the medial frontal gyri and the inferior parietal lobule. Our results provide evidence for functional remodeling of the somatosensory pathway and higher ordered multimodal brain areas occurring as a result of short-lasting tactile learning, and add to them a novel picture of extensive white matter plasticity.

Functional and Structural Neuroplasticity Induced by Short-Term Tactile Training Based on Braille Reading

PubMed Central

Debowska, Weronika; Wolak, Tomasz; Nowicka, Anna; Kozak, Anna; Szwed, Marcin; Kossut, Malgorzata

2016-01-01

Neuroplastic changes induced by sensory learning have been recognized within the cortices of specific modalities as well as within higher ordered multimodal areas. The interplay between these areas is not fully understood, particularly in the case of somatosensory learning. Here we examined functional and structural changes induced by short-term tactile training based of Braille reading, a task that requires both significant tactile expertise and mapping of tactile input onto multimodal representations. Subjects with normal vision were trained for 3 weeks to read Braille exclusively by touch and scanned before and after training, while performing a same-different discrimination task on Braille characters and meaningless characters. Functional and diffusion-weighted magnetic resonance imaging sequences were used to assess resulting changes. The strongest training-induced effect was found in the primary somatosensory cortex (SI), where we observed bilateral augmentation in activity accompanied by an increase in fractional anisotropy (FA) within the contralateral SI. Increases of white matter fractional anisotropy were also observed in the secondary somatosensory area (SII) and the thalamus. Outside of somatosensory system, changes in both structure and function were found in i.e., the fusiform gyrus, the medial frontal gyri and the inferior parietal lobule. Our results provide evidence for functional remodeling of the somatosensory pathway and higher ordered multimodal brain areas occurring as a result of short-lasting tactile learning, and add to them a novel picture of extensive white matter plasticity. PMID:27790087

Sports can protect dynamic visual acuity from aging: A study with young and older judo and karate martial arts athletes.

PubMed

Muiños, Mónica; Ballesteros, Soledad

2015-08-01

A major topic of current research in aging has been to investigate ways to promote healthy aging and neuroplasticity in order to counteract perceptual and cognitive declines. The aim of the present study was to investigate the benefits of intensive, sustained judo and karate martial arts training in young and older athletes and nonathletes of the same age for attenuating age-related dynamic visual acuity (DVA) decline. As a target, we used a moving stimulus similar to a Landolt ring that moved horizontally, vertically, or obliquely across the screen at three possible contrasts and three different speeds. The results indicated that (1) athletes had better DVA than nonathletes; (2) the older adult groups showed a larger oblique effect than the younger groups, regardless of whether or not they practiced a martial art; and (3) age modulated the results of sport under the high-speed condition: The DVA of young karate athletes was superior to that of nonathletes, while both judo and karate older athletes showed better DVA than did sedentary older adults. These findings suggest that in older adults, the practice of a martial art in general, rather than the practice of a particular type of martial art, is the crucial thing. We concluded that the sustained practice of a martial art such as judo or karate attenuates the decline of DVA, suggesting neuroplasticity in the aging human brain.

A BEHAVIORAL AND HISTOLOGICAL COMPARISON OF FLUID PERCUSSION INJURY AND CONTROLLED CORTICAL IMPACT INJURY TO THE RAT SENSORIMOTOR CORTEX

PubMed Central

Peterson, Todd C.; Maass, William R.; Anderson, Jordan R.; Anderson, Gail D.; Hoane, Michael R.

2015-01-01

Our primary goal was to evaluate the behavioral and histological outcome of fluid percussion injury (FPI) and cortical contusion injury (CCI) to the sensorimotor cortex (SMC). The SMC has been used to evaluate neuroplasticity following CCI, but has not been extensively examined with FPI. In both the CCI and FPI models, a mechanical force of 4 mm in diameter was applied over the SMC, allowing for a direct comparison to measure the relative rates of histology and recovery of function in these models. Gross behavioral deficits were found on the sensory task (tactile adhesive removal task) and multiple motor assessments (forelimb asymmetry task, forelimb placing task, and rotorod). These sensorimotor deficits occurred in the absence of cognitive deficits in the water maze. The CCI model creates focal damage with a localized injury wheras the FPI model creates a more diffuse injury causing widespread damage. Both behavioral and histological deficits ensued following both models of injury to the SMC. The neuroplastic changes and ease at which damage to this area can be measured behaviorally make this an excellent location to assess traumatic brain injury (TBI) treatments. No injury model can completely mimic the full spectrum of human TBI and any potential treatments should be validated across both focal and diffuse injury models. Both of these injury models to the SMC produce severe and enduring behavioral deficits, which are ideal for evaluating treatment options. PMID:26275924

Timing of motor cortical stimulation during planar robotic training differentially impacts neuroplasticity in older adults.

PubMed

Massie, Crystal L; Kantak, Shailesh S; Narayanan, Priya; Wittenberg, George F

2015-05-01

The objective was to determine how stimulation timing applied during reaching influenced neuroplasticity related to practice. Older adult participants were studied to increase relevance for stroke rehabilitation and aging. Sixteen participants completed 3 sessions of a reaching intervention with 480 planar robotic movement trials. Sub-threshold, single-pulse transcranial magnetic stimulations (TMS) were delivered during the late reaction time (LRT) period, when muscle activity exceeded a threshold (EMG-triggered), or randomly. Assessments included motor evoked potentials (MEP), amplitude, and direction of supra-threshold TMS-evoked movements and were calculated as change scores from baseline. The direction of TMS-evoked movements significantly changed after reaching practice (p<0.05), but was not significantly different between conditions. Movement amplitude changes were significantly different between conditions (p<0.05), with significant increases following the LRT and random conditions. MEP for elbow extensors and flexors, and the shoulder muscle that opposed the practice movement were significantly different between conditions with positive changes following LRT, negative changes following EMG-triggered, and no changes following the random condition. Motor performance including movement time and peak velocity significantly improved following the training but did not differ between conditions. The responsiveness of the motor cortex to stimulation was affected positively by stimulation during the late motor response period and negatively during the early movement period, when stimulation was combined with robotic reach practice. The sensitivity of the activated motor cortex to additional stimulation is highly dynamic. Copyright © 2015. Published by Elsevier Ireland Ltd.

Proteomic Analysis of Mitochondria-Enriched Fraction Isolated from the Frontal Cortex and Hippocampus of Apolipoprotein E Knockout Mice Treated with Alda-1, an Activator of Mitochondrial Aldehyde Dehydrogenase (ALDH2).

PubMed

Stachowicz, Aneta; Olszanecki, Rafał; Suski, Maciej; Głombik, Katarzyna; Basta-Kaim, Agnieszka; Adamek, Dariusz; Korbut, Ryszard

2017-02-17

The role of different genotypes of apolipoprotein E (apoE) in the etiology of Alzheimer's disease is widely recognized. It has been shown that altered functioning of apoE may promote 4-hydroxynonenal modification of mitochondrial proteins, which may result in mitochondrial dysfunction, aggravation of oxidative stress, and neurodegeneration. Mitochondrial aldehyde dehydrogenase (ALDH2) is an enzyme considered to perform protective function in mitochondria by the detoxification of the end products of lipid peroxidation, such as 4-hydroxynonenal and other reactive aldehydes. The goal of our study was to apply a differential proteomics approach in concert with molecular and morphological techniques to elucidate the changes in the frontal cortex and hippocampus of apolipoprotein E knockout (apoE -/- ) mice upon treatment with Alda-1-a small molecular weight activator of ALDH2. Despite the lack of significant morphological changes in the brain of apoE -/- mice as compared to age-matched wild type animals, the proteomic and molecular approach revealed many changes in the expression of genes and proteins, indicating the impairment of energy metabolism, neuroplasticity, and neurogenesis in brains of apoE -/- mice. Importantly, prolonged treatment of apoE -/- mice with Alda-1 led to the beneficial changes in the expression of genes and proteins related to neuroplasticity and mitochondrial function. The pattern of alterations implies mitoprotective action of Alda-1, however, the accurate functional consequences of the revealed changes require further research.

Potential protective effects of cannabidiol on neuroanatomical alterations in cannabis users and psychosis: a critical review.

PubMed

Hermann, Derik; Schneider, Miriam

2012-01-01

Cannabis use and the development of schizophrenic psychoses share a variety of similarities. Both start during late adolescence; go along with neuropsychological deficits, reduced activity, motivation deficits, and hallucinations suggesting impairment of similar brain structures. In cannabis heavy users diminished regional gray and white matter volume was reported. Similar alterations were observed in the large literature addressing structural abnormalities in schizophrenia. Furthermore, in cannabis using schizophrenic patients, these brain alterations were especially pronounced. Close relatives of schizophrenic patients showed greater cannabis-associated brain tissue loss than non-relatives indicating a genetically mediated particular sensitivity to brain tissue loss. Possible mechanisms for the induction of structural brain alterations are here discussed including impairments of neurogenesis, disturbance of endocannabinoids and diminished neuroplasticity. Especially direct THC effects (or via endocannabinoids) may mediate diminished glutamatergic neurotransmission usually driving neuroplasticity. Correspondingly, alterations of the kynurenic acid blocking NMDA receptors may contribute to brain structure alterations. However, different cannabis compounds may exert opposite effects on the neuroanatomical changes underlying psychosis. In particular, cannabidiol (CBD) was shown to prevent THC associated hippocampal volume loss in a small pilot study. This finding is further supported by several animal experiments supporting neuroprotective properties of CBD mainly via anti-oxidative effects, CB2 receptors or adenosine receptors. We will discuss here the mechanisms by which CBD may reduce brain volume loss, including antagonism of THC, interactions with endocannabinoids, and mechanisms that specifically underlie antipsychotic properties of CBD.

Spaceflight-induced neuroplasticity in humans as measured by MRI: what do we know so far?

PubMed

Van Ombergen, Angelique; Laureys, Steven; Sunaert, Stefan; Tomilovskaya, Elena; Parizel, Paul M; Wuyts, Floris L

2017-01-01

Space travel poses an enormous challenge on the human body; microgravity, ionizing radiation, absence of circadian rhythm, confinement and isolation are just some of the features associated with it. Obviously, all of the latter can have an impact on human physiology and even induce detrimental changes. Some organ systems have been studied thoroughly under space conditions, however, not much is known on the functional and morphological effects of spaceflight on the human central nervous system. Previous studies have already shown that central nervous system changes occur during and after spaceflight in the form of neurovestibular problems, alterations in cognitive function and sensory perception, cephalic fluid shifts and psychological disturbances. However, little is known about the underlying neural substrates. In this review, we discuss the current limited knowledge on neuroplastic changes in the human central nervous system associated with spaceflight (actual or simulated) as measured by magnetic resonance imaging-based techniques. Furthermore, we discuss these findings as well as their future perspectives, since this can encourage future research into this delicate and intriguing aspect of spaceflight. Currently, the literature suffers from heterogeneous experimental set-ups and therefore, the lack of comparability of findings among studies. However, the cerebellum, cortical sensorimotor and somatosensory areas and vestibular-related pathways seem to be involved across different studies, suggesting that these brain regions are most affected by (simulated) spaceflight. Extending this knowledge is crucial, especially with the eye on long-duration interplanetary missions (e.g. Mars) and space tourism.

Commonly-occurring polymorphisms in the COMT, DRD1 and DRD2 genes influence different aspects of motor sequence learning in humans.

PubMed

Baetu, Irina; Burns, Nicholas R; Urry, Kristi; Barbante, Girolamo Giovanni; Pitcher, Julia B

2015-11-01

Performing sequences of movements is a ubiquitous skill that involves dopamine transmission. However, it is unclear which components of the dopamine system contribute to which aspects of motor sequence learning. Here we used a genetic approach to investigate the relationship between different components of the dopamine system and specific aspects of sequence learning in humans. In particular, we investigated variations in genes that code for the catechol-O-methyltransferase (COMT) enzyme, the dopamine transporter (DAT) and dopamine D1 and D2 receptors (DRD1 and DRD2). COMT and the DAT regulate dopamine availability in the prefrontal cortex and the striatum, respectively, two key regions recruited during learning, whereas dopamine D1 and D2 receptors are thought to be involved in long-term potentiation and depression, respectively. We show that polymorphisms in the COMT, DRD1 and DRD2 genes differentially affect behavioral performance on a sequence learning task in 161 Caucasian participants. The DRD1 polymorphism predicted the ability to learn new sequences, the DRD2 polymorphism predicted the ability to perform a previously learnt sequence after performing interfering random movements, whereas the COMT polymorphism predicted the ability to switch flexibly between two sequences. We used computer simulations to explore potential mechanisms underlying these effects, which revealed that the DRD1 and DRD2 effects are possibly related to neuroplasticity. Our prediction-error algorithm estimated faster rates of connection strengthening in genotype groups with presumably higher D1 receptor densities, and faster rates of connection weakening in genotype groups with presumably higher D2 receptor densities. Consistent with current dopamine theories, these simulations suggest that D1-mediated neuroplasticity contributes to learning to select appropriate actions, whereas D2-mediated neuroplasticity is involved in learning to inhibit incorrect action plans. However, the learning algorithm did not account for the COMT effect, suggesting that prefrontal dopamine availability might affect sequence switching via other, non-learning, mechanisms. These findings provide insight into the function of the dopamine system, which is relevant to the development of treatments for disorders such as Parkinson's disease. Our results suggest that treatments targeting dopamine D1 receptors may improve learning of novel sequences, whereas those targeting dopamine D2 receptors may improve the ability to initiate previously learned sequences of movements. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Leveraging the Skills of Nurses and the Power of Language Nutrition to Ensure a Better Future for Children.

PubMed

Darcy Mahoney, Ashley; Zauche, Lauren Head; Hallowell, Sunny; Weldon, Arianne; Stapel-Wax, Jennifer

2017-02-01

Early language exposure is critical for language acquisition and significantly influences a child's literacy skills. However, preterm infants may experience language deprivation in the neonatal intensive care unit. Nurses are vital to helping parents understand their critical role in early language development. To discuss the impact of language-rich interactions and interventions that promote early language exposure, or Language Nutrition, by parents and caregivers on the long-term developmental, language, and educational outcomes of high-risk infants. A literature search was conducted using PubMed and Web of Science to identify articles that examined the influence of language interactions with high-risk infants on developmental outcomes. Recent campaigns touting the importance of early language exposure were identified through the Bridging the Word Gap Research Network. Increasing preterm infants' exposure to Language Nutrition improves their language development, promotes parent-infant attachment, and decreases parent stress. In addition, it may result in greater neuroplasticity and volume of the auditory cortex. Several campaigns have been developed to increase children's access to Language Nutrition and can be implemented into everyday pediatric and neonatal care. Pediatric, neonatal nurses and advanced practice nurses are uniquely positioned to play a transformational role in high-risk infants' developmental trajectory by educating parents about the importance of Language Nutrition and supporting parents as they engage with their infant. Studies investigating the population-level impact of interventions aimed at increasing infants' access to Language Nutrition as well as studies identifying effective ways to communicate messages about Language Nutrition are warranted.

Chronic minocycline treatment improves hippocampal neuronal structure, NMDA receptor function, and memory processing in Fmr1 knockout mice.

PubMed

Yau, S Y; Bettio, Luis; Vetrici, M; Truesdell, A; Chiu, C; Chiu, J; Truesdell, E; Christie, B R

2018-05-01

Fragile X Syndrome (FXS) is the most common inherited cause of intellectual disability, and is the leading known single-gene cause of autism spectrum disorder. FXS patients display varied behavioural deficits that include mild to severe cognitive impairments in addition to mood disorders. Currently there is no cure for this condition, however minocycline is becoming commonly prescribed as a treatment for FXS patients. Minocycline has been reported to alleviate social behavioural deficits, and improve verbal functioning in patients with FXS; however, its mode of action is not well understood. Previously we have shown that FXS results in learning impairments that involve deficits in N-methyl-d-aspartate (NMDA) receptor-dependent synaptic plasticity in the hippocampal dentate gyrus (DG). Here we tested whether chronic treatment with minocycline can improve these deficits by enhancing NMDA receptor-dependent functional and structural plasticity in the DG. Minocycline treatment resulted in a significant enhancement in NMDA receptor function in the dentate granule cells. This was accompanied by an increase in PSD-95 and GluN2A and GluN2B subunits in hippocampal synaptoneurosome fractions. Minocycline treatment also enhanced dentate granule cell dendritic length and branching. In addition, our results show that chronic minocycline treatment can rescue performance in novel object recognition in FXS mice. These findings indicate that minocycline treatment has both structural and functional benefits for hippocampal cells, which may partly contribute to the pro-cognitive effects minocycline appears to have for treating FXS. Copyright © 2018 Elsevier Inc. All rights reserved.

Closed-loop brain training: the science of neurofeedback.

PubMed

Sitaram, Ranganatha; Ros, Tomas; Stoeckel, Luke; Haller, Sven; Scharnowski, Frank; Lewis-Peacock, Jarrod; Weiskopf, Nikolaus; Blefari, Maria Laura; Rana, Mohit; Oblak, Ethan; Birbaumer, Niels; Sulzer, James

2017-02-01

Neurofeedback is a psychophysiological procedure in which online feedback of neural activation is provided to the participant for the purpose of self-regulation. Learning control over specific neural substrates has been shown to change specific behaviours. As a progenitor of brain-machine interfaces, neurofeedback has provided a novel way to investigate brain function and neuroplasticity. In this Review, we examine the mechanisms underlying neurofeedback, which have started to be uncovered. We also discuss how neurofeedback is being used in novel experimental and clinical paradigms from a multidisciplinary perspective, encompassing neuroscientific, neuroengineering and learning-science viewpoints.

A Brain Centred View of Psychiatric Comorbidity in Tinnitus: From Otology to Hodology

PubMed Central

Minichino, Amedeo; Panico, Roberta; Testugini, Valeria; Altissimi, Giancarlo; Cianfrone, Giancarlo

2014-01-01

Introduction. Comorbid psychiatric disorders are frequent among patients affected by tinnitus. There are mutual clinical influences between tinnitus and psychiatric disorders, as well as neurobiological relations based on partially overlapping hodological and neuroplastic phenomena. The aim of the present paper is to review the evidence of alterations in brain networks underlying tinnitus physiopathology and to discuss them in light of the current knowledge of the neurobiology of psychiatric disorders. Methods. Relevant literature was identified through a search on Medline and PubMed; search terms included tinnitus, brain, plasticity, cortex, network, and pathways. Results. Tinnitus phenomenon results from systemic-neurootological triggers followed by neuronal remapping within several auditory and nonauditory pathways. Plastic reorganization and white matter alterations within limbic system, arcuate fasciculus, insula, salience network, dorsolateral prefrontal cortex, auditory pathways, ffrontocortical, and thalamocortical networks are discussed. Discussion. Several overlapping brain network alterations do exist between tinnitus and psychiatric disorders. Tinnitus, initially related to a clinicoanatomical approach based on a cortical localizationism, could be better explained by an holistic or associationist approach considering psychic functions and tinnitus as emergent properties of partially overlapping large-scale neural networks. PMID:25018882

Maladaptive plasticity in tinnitus-triggers, mechanisms and treatment

PubMed Central

Shore, Susan E; Roberts, Larry E.; Langguth, Berthold

2016-01-01

Tinnitus is a phantom auditory sensation that reduces quality of life for millions worldwide and for which there is no medical cure. Most cases are associated with hearing loss caused by the aging process or noise exposure. Because exposure to loud recreational sound is common among youthful populations, young persons are at increasing risk. Head or neck injuries can also trigger the development of tinnitus, as altered somatosensory input can affect auditory pathways and lead to tinnitus or modulate its intensity. Emotional and attentional state may play a role in tinnitus development and maintenance via top-down mechanisms. Thus, military in combat are particularly at risk due to combined hearing loss, somatosensory system disturbances and emotional stress. Neuroscience research has identified neural changes related to tinnitus that commence at the cochlear nucleus and extend to the auditory cortex and brain regions beyond. Maladaptive neural plasticity appears to underlie these neural changes, as it results in increased spontaneous firing rates and synchrony among neurons in central auditory structures that may generate the phantom percept. This review highlights the links between animal and human studies, including several therapeutic approaches that have been developed, which aim to target the neuroplastic changes underlying tinnitus. PMID:26868680

Longitudinal connectome-based predictive modeling for REM sleep behavior disorder from structural brain connectivity

NASA Astrophysics Data System (ADS)

Giancardo, Luca; Ellmore, Timothy M.; Suescun, Jessika; Ocasio, Laura; Kamali, Arash; Riascos-Castaneda, Roy; Schiess, Mya C.

2018-02-01

Methods to identify neuroplasticity patterns in human brains are of the utmost importance in understanding and potentially treating neurodegenerative diseases. Parkinson disease (PD) research will greatly benefit and advance from the discovery of biomarkers to quantify brain changes in the early stages of the disease, a prodromal period when subjects show no obvious clinical symptoms. Diffusion tensor imaging (DTI) allows for an in-vivo estimation of the structural connectome inside the brain and may serve to quantify the degenerative process before the appearance of clinical symptoms. In this work, we introduce a novel strategy to compute longitudinal structural connectomes in the context of a whole-brain data-driven pipeline. In these initial tests, we show that our predictive models are able to distinguish controls from asymptomatic subjects at high risk of developing PD (REM sleep behavior disorder, RBD) with an area under the receiving operating characteristic curve of 0.90 (p<0.001) and a longitudinal dataset of 46 subjects part of the Parkinson's Progression Markers Initiative. By analyzing the brain connections most relevant for the predictive ability of the best performing model, we find connections that are biologically relevant to the disease.

5-HT1 receptor augmentation strategies as enhanced efficacy: therapeutics for psychiatric disorders.

PubMed

Dawson, Lee A; Bromidge, Steve M

2008-01-01

Since the initial observations linking 5-HT to psychiatric illness, evidence for a role of 5-HT and, in particular, a decreased brain serotonergic function in the pathology of a plethora of related disorders, has grown. However, it is the role of 5-HT in the pathogenesis of anxiety disorders and depression and the mechanism of action of antidepressants which has received the most attention. Thus enhanced serotonergic neurotransmission has become one of the unifying mechanisms of action of modern day antidepressants/anxiolytics such as monoamine oxidase inhibitors, tricyclic antidepressants, and serotonin reuptake inhibitors. Interestingly all of these treatments are associated with a delay to therapeutic efficacy and in some cases treatment resistance, despite immediate enhancements in serotonergic neurotransmission. The postulated reason for this is the need for temporal neuroplastic changes in the control of serotonergic neurotransmission, and more specifically changes in 5-HT(1) autoreceptor function. Thus significant research has gone into pharmacologically targeting these 5-HT(1) autoreceptors as a means of augmenting the efficacy of current therapeutic mechanisms. Here we will review the rationale behind the various augmentation strategies adopted and the progress made in identifying novel therapeutics for conditions such as depression and anxiety disorders.

Lateralization of brain activation in fluent and non-fluent preschool children: a magnetoencephalographic study of picture-naming.

PubMed

Sowman, Paul F; Crain, Stephen; Harrison, Elisabeth; Johnson, Blake W

2014-01-01

The neural causes of stuttering remain unknown. One explanation comes from neuroimaging studies that have reported abnormal lateralization of activation in the brains of people who stutter. However, these findings are generally based on data from adults with a long history of stuttering, raising the possibility that the observed lateralization anomalies are compensatory rather than causal. The current study investigated lateralization of brain activity in language-related regions of interest in young children soon after the onset of stuttering. We tested 24 preschool-aged children, half of whom had a positive diagnosis of stuttering. All children participated in a picture-naming experiment whilst their brain activity was recorded by magnetoencephalography. Source analysis performed during an epoch prior to speech onset was used to assess lateralized activation in three regions of interest. Activation was significantly lateralized to the left hemisphere in both groups and not different between groups. This study shows for the first time that significant speech preparatory brain activation can be identified in young children during picture-naming and supports the contention that, in stutterers, aberrant lateralization of brain function may be the result of neuroplastic adaptation that occurs as the condition becomes chronic.

Sleep Spindle Characteristics in Children with Neurodevelopmental Disorders and Their Relation to Cognition

PubMed Central

Wise, Merrill S.

2016-01-01

Empirical evidence indicates that sleep spindles facilitate neuroplasticity and “off-line” processing during sleep, which supports learning, memory consolidation, and intellectual performance. Children with neurodevelopmental disorders (NDDs) exhibit characteristics that may increase both the risk for and vulnerability to abnormal spindle generation. Despite the high prevalence of sleep problems and cognitive deficits in children with NDD, only a few studies have examined the putative association between spindle characteristics and cognitive function. This paper reviews the literature regarding sleep spindle characteristics in children with NDD and their relation to cognition in light of what is known in typically developing children and based on the available evidence regarding children with NDD. We integrate available data, identify gaps in understanding, and recommend future research directions. Collectively, studies are limited by small sample sizes, heterogeneous populations with multiple comorbidities, and nonstandardized methods for collecting and analyzing findings. These limitations notwithstanding, the evidence suggests that future studies should examine associations between sleep spindle characteristics and cognitive function in children with and without NDD, and preliminary findings raise the intriguing question of whether enhancement or manipulation of sleep spindles could improve sleep-dependent memory and other aspects of cognitive function in this population. PMID:27478646

Secrets of virtuoso: neuromuscular attributes of motor virtuosity in expert musicians

PubMed Central

Furuya, Shinichi; Oku, Takanori; Miyazaki, Fumio; Kinoshita, Hiroshi

2015-01-01

Musical performance requires extremely fast and dexterous limb movements. The underlying biological mechanisms have been an object of interest among scientists and non-scientists for centuries. Numerous studies of musicians and non-musicians have demonstrated that neuroplastic adaptations through early and deliberate musical training endowed superior motor skill. However, little has been unveiled about what makes inter-individual differences in motor skills among musicians. Here we determined the attributes of inter-individual differences in the maximum rate of repetitive piano keystrokes in twenty-four pianists. Among various representative factors of neuromuscular functions, anatomical characteristics, and training history, a stepwise multiple regression analysis and generalized linear model identified two predominant predictors of the maximum rate of repetitive piano keystrokes; finger tapping rate and muscular strength of the elbow extensor. These results suggest a non-uniform role of individual limb muscles in the production of extremely fast repetitive multi-joint movements. Neither age of musical training initiation nor the amount of extensive musical training before age twenty was a predictor. Power grip strength was negatively related to the maximum rate of piano keystrokes only during the smallest tone production. These findings highlight the importance of innate biological nature and explicit training for motor virtuosity. PMID:26502770

Atypical handedness in mesial temporal lobe epilepsy.

PubMed

Doležalová, Irena; Schachter, Steven; Chrastina, Jan; Hemza, Jan; Hermanová, Markéta; Rektor, Ivan; Pažourková, Marta; Brázdil, Milan

2017-07-01

The main aim of our study was to investigate the handedness of patients with mesial temporal lobe epilepsy (MTLE). We also sought to identify clinical variables that correlated with left-handedness in this population. Handedness (laterality quotient) was assessed in 73 consecutive patients with MTLE associated with unilateral hippocampal sclerosis (HS) using the Edinburgh Handedness Inventory. Associations between right- and left-handedness and clinical variables were investigated. We found that 54 (74.0%) patients were right-handed, and 19 (26%) patients were left-handed. There were 15 (36.6%) left-handed patients with left-sided seizure onset compared to 4 (12.5%) left-handed patients with right-sided seizure onset (p=0.030). Among patients with left-sided MTLE, age at epilepsy onset was significantly correlated with handedness (8years of age [median; min-max 0.5-17] in left-handers versus 15years of age [median; min-max 3-30] in right-handers (p<0.001). Left-sided MTLE is associated with atypical handedness, especially when seizure onset occurs during an active period of brain development, suggesting a bi-hemispheric neuroplastic process for establishing motor dominance in patients with early-onset left-sided MTLE. Copyright © 2017 Elsevier Inc. All rights reserved.

Reducing excessive GABAergic tonic inhibition promotes post-stroke functional recovery

PubMed Central

Clarkson, Andrew N.; Huang, Ben S.; MacIsaac, Sarah E.; Mody, Istvan; Carmichael, S. Thomas

2010-01-01

Stroke is a leading cause of disability; but no pharmacological therapy is currently available for promoting recovery. The brain region adjacent to stroke damage, the peri-infarct zone, is critical for rehabilitation, as it exhibits heightened neuroplasticity, allowing sensorimotor functions to re-map from damaged areas1–3. Thus, understanding the neuronal properties constraining this plasticity is important to developing new treatments. Here we show that after a stroke in mice, tonic neuronal inhibition is increased in the peri-infarct zone. This increased tonic inhibition is mediated by extrasynaptic GABAA receptors (GABAARs) and is caused by an impairment in GABA transporter (GAT-3/4) function. To counteract the heightened inhibition, we administered in vivo a benzodiazepine inverse agonist specific for the α5-subunit-containing extrasynaptic GABAARs at a delay after stroke. This treatment produced an early and sustained recovery of motor function. Genetically lowering the number of α5 or δ-subunit-containing GABAARs responsible for tonic inhibition also proved beneficial for post-stroke recovery, consistent with the therapeutic potential of diminishing extrasynaptic GABAAR function. Together, our results identify new pharmacological targets and provide the rationale for a novel strategy to promote recovery after stroke and possibly other brain injuries. PMID:21048709

Borderline personality disorder and childhood trauma: exploring the affected biological systems and mechanisms.

PubMed

Cattane, Nadia; Rossi, Roberta; Lanfredi, Mariangela; Cattaneo, Annamaria

2017-06-15

According to several studies, the onset of the Borderline Personality Disorder (BPD) depends on the combination between genetic and environmental factors (GxE), in particular between biological vulnerabilities and the exposure to traumatic experiences during childhood. We have searched for studies reporting possible alterations in several biological processes and brain morphological features in relation to childhood trauma experiences and to BPD. We have also looked for epigenetic mechanisms as they could be mediators of the effects of childhood trauma in BPD vulnerability. We prove the role of alterations in Hypothalamic-Pituitary-Adrenal (HPA) axis, in neurotrasmission, in the endogenous opioid system and in neuroplasticity in the childhood trauma-associated vulnerability to develop BPD; we also confirm the presence of morphological changes in several BPD brain areas and in particular in those involved in stress response. Not so many studies are available on epigenetic changes in BPD patients, although these mechanisms are widely investigated in relation to stress-related disorders. A better comprehension of the biological and epigenetic mechanisms, affected by childhood trauma and altered in BPD patients, could allow to identify "at high risk" subjects and to prevent or minimize the development of the disease later in life.

Secrets of virtuoso: neuromuscular attributes of motor virtuosity in expert musicians

NASA Astrophysics Data System (ADS)

Furuya, Shinichi; Oku, Takanori; Miyazaki, Fumio; Kinoshita, Hiroshi

2015-10-01

Musical performance requires extremely fast and dexterous limb movements. The underlying biological mechanisms have been an object of interest among scientists and non-scientists for centuries. Numerous studies of musicians and non-musicians have demonstrated that neuroplastic adaptations through early and deliberate musical training endowed superior motor skill. However, little has been unveiled about what makes inter-individual differences in motor skills among musicians. Here we determined the attributes of inter-individual differences in the maximum rate of repetitive piano keystrokes in twenty-four pianists. Among various representative factors of neuromuscular functions, anatomical characteristics, and training history, a stepwise multiple regression analysis and generalized linear model identified two predominant predictors of the maximum rate of repetitive piano keystrokes; finger tapping rate and muscular strength of the elbow extensor. These results suggest a non-uniform role of individual limb muscles in the production of extremely fast repetitive multi-joint movements. Neither age of musical training initiation nor the amount of extensive musical training before age twenty was a predictor. Power grip strength was negatively related to the maximum rate of piano keystrokes only during the smallest tone production. These findings highlight the importance of innate biological nature and explicit training for motor virtuosity.

A Protocol for the Administration of Real-Time fMRI Neurofeedback Training

PubMed Central

Sherwood, Matthew S.; Diller, Emily E.; Ey, Elizabeth; Ganapathy, Subhashini; Nelson, Jeremy T.; Parker, Jason G.

2017-01-01

Neurologic disorders are characterized by abnormal cellular-, molecular-, and circuit-level functions in the brain. New methods to induce and control neuroplastic processes and correct abnormal function, or even shift functions from damaged tissue to physiologically healthy brain regions, hold the potential to dramatically improve overall health. Of the current neuroplastic interventions in development, neurofeedback training (NFT) from functional Magnetic Resonance Imaging (fMRI) has the advantages of being completely non-invasive, non-pharmacologic, and spatially localized to target brain regions, as well as having no known side effects. Furthermore, NFT techniques, initially developed using fMRI, can often be translated to exercises that can be performed outside of the scanner without the aid of medical professionals or sophisticated medical equipment. In fMRI NFT, the fMRI signal is measured from specific regions of the brain, processed, and presented to the participant in real-time. Through training, self-directed mental processing techniques, that regulate this signal and its underlying neurophysiologic correlates, are developed. FMRI NFT has been used to train volitional control over a wide range of brain regions with implications for several different cognitive, behavioral, and motor systems. Additionally, fMRI NFT has shown promise in a broad range of applications such as the treatment of neurologic disorders and the augmentation of baseline human performance. In this article, we present an fMRI NFT protocol developed at our institution for modulation of both healthy and abnormal brain function, as well as examples of using the method to target both cognitive and auditory regions of the brain. PMID:28872110

Virtual Reality to Maximize Function for Hand and Arm Rehabilitation: Exploration of Neural Mechanisms

PubMed Central

MERIANS, Alma S.; TUNIK, Eugene; ADAMOVICH, Sergei V.

2015-01-01

Stroke patients report hand function as the most disabling motor deficit. Current evidence shows that learning new motor skills is essential for inducing functional neuroplasticity and functional recovery. Adaptive training paradigms that continually and interactively move a motor outcome closer to the targeted skill are important to motor recovery. Computerized virtual reality simulations when interfaced with robots, movement tracking and sensing glove systems are particularly adaptable, allowing for online and offline modifications of task based activities using the participant’s current performance and success rate. We have developed a second generation system that can exercise the hand and the arm together or in isolation and provides for both unilateral and bilateral hand and arm activities in three-dimensional space. We demonstrate that by providing haptic assistance for the hand and arm and adaptive anti-gravity support, the system can accommodate patients with lower level impairments. We hypothesize that combining training in VE with observation of motor actions can bring additional benefits. We present a proof of concept of a novel system that integrates interactive VE with functional neuroimaging to address this issue. Three components of this system are synchronized, the presentation of the visual display of the virtual hands, the collection of fMRI images and the collection of hand joint angles from the instrumented gloves. We show that interactive VEs can facilitate activation of brain areas during training by providing appropriately modified visual feedback. We predict that visual augmentation can become a tool to facilitate functional neuroplasticity. PMID:19592790

A Protocol for the Administration of Real-Time fMRI Neurofeedback Training.

PubMed

Sherwood, Matthew S; Diller, Emily E; Ey, Elizabeth; Ganapathy, Subhashini; Nelson, Jeremy T; Parker, Jason G

2017-08-24

Neurologic disorders are characterized by abnormal cellular-, molecular-, and circuit-level functions in the brain. New methods to induce and control neuroplastic processes and correct abnormal function, or even shift functions from damaged tissue to physiologically healthy brain regions, hold the potential to dramatically improve overall health. Of the current neuroplastic interventions in development, neurofeedback training (NFT) from functional Magnetic Resonance Imaging (fMRI) has the advantages of being completely non-invasive, non-pharmacologic, and spatially localized to target brain regions, as well as having no known side effects. Furthermore, NFT techniques, initially developed using fMRI, can often be translated to exercises that can be performed outside of the scanner without the aid of medical professionals or sophisticated medical equipment. In fMRI NFT, the fMRI signal is measured from specific regions of the brain, processed, and presented to the participant in real-time. Through training, self-directed mental processing techniques, that regulate this signal and its underlying neurophysiologic correlates, are developed. FMRI NFT has been used to train volitional control over a wide range of brain regions with implications for several different cognitive, behavioral, and motor systems. Additionally, fMRI NFT has shown promise in a broad range of applications such as the treatment of neurologic disorders and the augmentation of baseline human performance. In this article, we present an fMRI NFT protocol developed at our institution for modulation of both healthy and abnormal brain function, as well as examples of using the method to target both cognitive and auditory regions of the brain.

The potential role of neuropathic mechanisms in dry eye syndromes.

PubMed

Mcmonnies, Charles W

Dry eye syndromes can involve both nociceptive and neuropathic symptoms. Nociceptive symptoms are the normal physiological responses to noxious stimuli. Neuropathic symptoms are caused by a lesion or disease of the somatosensory nervous system and can be the result of hypersensitisation of peripheral or central corneal and conjunctival somatosensory nerves. For example, inflammation could induce neuroplastic peripheral sensitisation of the ocular surface or lid wiper and exacerbate nociceptive symptoms. Neuropathic symptoms may explain the incommensurate relation between signs and symptoms in some dry eye syndromes although absence of signs of a dry eye syndrome may also be a consequence of inappropriate methods used when examining for them. Involvement of neuropathic mechanisms may also help explain dry eye symptoms which occur in association with reduced corneal sensitivity. This review includes a discussion of the potential for ocular symptoms involving neuropathic mechanisms to contribute to psychosocial problems such as depression, stress, anxiety and sleep disorders as well as for these types of psychosocial problems to contribute to neuropathic mechanisms and dry eye syndromes. Failure to consider the possibility that neuropathic mechanisms can contribute to dry eye syndromes may reduce accuracy of diagnosis and the suitability of treatment provided. Dry eye symptoms in the absence of commensurate evidence of tear dysfunction, and unsatisfactory response to tear dysfunction therapies should prompt consideration of neuropathic mechanisms being involved. Symptoms which persist after local anaesthetic instillation are more likely to be neuropathic in origin. Reducing inflammation may help limit any associated neuroplastic hypersensitivity. Copyright © 2016 Spanish General Council of Optometry. Published by Elsevier España, S.L.U. All rights reserved.

Epigenetic regulation of opioid-induced hyperalgesia, dependence, and tolerance in mice.

PubMed

Liang, De-Yong; Li, XiangQi; Clark, J David

2013-01-01

Repeated administration of opioids such as morphine induces persistent behavioral changes including opioid-induced hyperalgesia (OIH), tolerance, and physical dependence. In the current work we explored how the balance of histone acetyltransferase (HAT) versus histone deacetylase (HDAC) might regulate these morphine-induced changes. Nociceptive thresholds, analgesia, and physical dependence were assessed during and for a period of several weeks after morphine exposure. To probe the roles of histone acetylation, the HAT inhibitor curcumin or a selective HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) was administered daily to groups of animals. Histone acetylation in spinal cord was assessed by Western blot and immunohistochemistry. Concurrent administration of curcumin with morphine for 4 days significantly reduced development of opioid-induced mechanical allodynia, thermal hyperalgesia, tolerance, and physical dependence. Conversely, the HDAC inhibitor SAHA enhanced these responses. Interestingly, SAHA treatment after the termination of opioid administration sustained these behavioral changes for at least 4 weeks. Histone H3 acetylation in the dorsal horn of the spinal cord was increased after chronic morphine treatment, but H4 acetylation was unchanged. Moreover, we observed a decrease in HDAC activity in the spinal cords of morphine-treated mice while overall HAT activity was unchanged, suggesting a shift toward a state of enhanced histone acetylation. The current study indicates that epigenetic mechanisms play a crucial role in opioid-induced long-lasting neuroplasticity. These results provide new sight into understanding the mechanisms of opioid-induced neuroplasticity and suggest new strategies to limit opioid abuse potential and increase the value of these drugs as analgesics. Copyright © 2013 American Pain Society. All rights reserved.

Effects of Anodal Transcranial Direct Current Stimulation and Serotonergic Enhancement on Memory Performance in Young and Older Adults.

PubMed

Prehn, Kristin; Stengl, Helena; Grittner, Ulrike; Kosiolek, René; Ölschläger, Anja; Weidemann, Alexandra; Flöel, Agnes

2017-01-01

In the absence of effective therapies for dementia and its precursors, enhancing neuroplasticity by means of non-invasive brain stimulation such as anodal transcranial direct current stimulation (atDCS) might be a promising approach to counteract or delay the onset of cognitive decline, but effect sizes have been moderate so far. Previous reports indicate that increasing serotonin levels may enhance atDCS-induced neuroplasticity. However, evidence for serotonergic modulation of atDCS effects on memory is still lacking. Here, we conducted a double-blind, randomized, sham-/placebo-controlled trial to investigate the impact of a selective serotonin reuptake inhibitor (SSRI; single dose of 20 mg citalopram) and atDCS over the right temporoparietal cortex (1 mA, 20 min) on memory formation. Twenty young and 20 older subjects completed an object-location learning task in each of the four conditions: sham+placebo, sham+SSRI, atDCS+placebo, and atDCS+SSRI. Outcome measures were performance in immediate (primary outcome) and delayed cued recall. While we found an SSRI effect, but no statistically significant effect of atDCS on immediate recall scores, young and older adults benefited most from the combined application (comparisons: atDCS+SSRI>atDCS+placebo and atDCS+SSRI>sham+placebo). Thus, our data provide evidence that atDCS improves memory formation if serotonergic neurotransmission is enhanced simultaneously. Further studies are needed to assess whether these findings extend to clinical populations with memory impairment and translate into clinically relevant improvements after long-term serotonergic enhancement and repeated stimulation.

Effects of Anodal Transcranial Direct Current Stimulation and Serotonergic Enhancement on Memory Performance in Young and Older Adults

PubMed Central

Prehn, Kristin; Stengl, Helena; Grittner, Ulrike; Kosiolek, René; Ölschläger, Anja; Weidemann, Alexandra; Flöel, Agnes

2017-01-01

In the absence of effective therapies for dementia and its precursors, enhancing neuroplasticity by means of non-invasive brain stimulation such as anodal transcranial direct current stimulation (atDCS) might be a promising approach to counteract or delay the onset of cognitive decline, but effect sizes have been moderate so far. Previous reports indicate that increasing serotonin levels may enhance atDCS-induced neuroplasticity. However, evidence for serotonergic modulation of atDCS effects on memory is still lacking. Here, we conducted a double-blind, randomized, sham-/placebo-controlled trial to investigate the impact of a selective serotonin reuptake inhibitor (SSRI; single dose of 20 mg citalopram) and atDCS over the right temporoparietal cortex (1 mA, 20 min) on memory formation. Twenty young and 20 older subjects completed an object-location learning task in each of the four conditions: sham+placebo, sham+SSRI, atDCS+placebo, and atDCS+SSRI. Outcome measures were performance in immediate (primary outcome) and delayed cued recall. While we found an SSRI effect, but no statistically significant effect of atDCS on immediate recall scores, young and older adults benefited most from the combined application (comparisons: atDCS+SSRI>atDCS+placebo and atDCS+SSRI>sham+placebo). Thus, our data provide evidence that atDCS improves memory formation if serotonergic neurotransmission is enhanced simultaneously. Further studies are needed to assess whether these findings extend to clinical populations with memory impairment and translate into clinically relevant improvements after long-term serotonergic enhancement and repeated stimulation. PMID:27555381

Skill-Specific Changes in Somatosensory Nogo Potentials in Baseball Players

PubMed Central

Yamashiro, Koya; Sato, Daisuke; Onishi, Hideaki; Sugawara, Kazuhiro; Nakazawa, Sho; Shimojo, Hirofumi; Akatsuka, Kosuke; Nakata, Hiroki; Maruyama, Atsuo

2015-01-01

Athletic training is known to induce neuroplastic alterations in specific somatosensory circuits, which are reflected by changes in somatosensory evoked potentials and event-related potentials. The aim of this study was to clarify whether specific athletic training also affects somatosensory Nogo potentials related to the inhibition of movements. The Nogo potentials were recorded at nine cortical electrode positions (Fz, Cz, Pz, F3, F4, C3, C4, P3 and P4) in 12 baseball players (baseball group) and in 12 athletes in sports, such as track and field events and swimming, that do not require response inhibition, such as batting for training or performance (sports group). The Nogo potentials and Go/Nogo reaction times (Go/Nogo RTs) were measured under a somatosensory Go/Nogo paradigm in which subjects were instructed to rapidly push a button in response to stimulus presentation. The Nogo potentials were obtained by subtracting the Go trial from the Nogo trial. The peak Nogo-N2 was significantly shorter in the baseball group than that in the sports group. In addition, the amplitude of Nogo-N2 in the frontal area was significantly larger in the baseball group than that in the sports group. There was a significant positive correlation between the latency of Nogo-N2 and Go/Nogo RT. Moreover, there were significant correlations between the Go/Nogo RT and both the amplitude of Nogo-N2 and Nogo-P3 (i.e., amplitude of the Nogo-potentials increases with shorter RT). Specific athletic training regimens may induce neuroplastic alterations in sensorimotor inhibitory processes. PMID:26600391

Intraoperative linguistic performance during awake brain surgery predicts postoperative linguistic deficits.

PubMed

Chang, Wei-Han; Pei, Yu-Cheng; Wei, Kuo-Chen; Chao, Yi-Ping; Chen, Mei-Hui; Yeh, Heng-An; Jaw, Fu-Shan; Chen, Pin-Yuan

2018-04-10

Awake craniotomy pursues a balance between extensive tumor resection and preservation of postoperative language function. A dilemma exists in patients whose tumor resection is restricted due to signs of language impairment observed during awake craniotomy. In order to determine the degree to which recovery of language function caused by tumor resection can be achieved by spontaneous neuroplasticity, the change in postoperative language function was compared to quantified intraoperative linguistic performance. The modified, short-form Boston Diagnostic Aphasia Examination (sfBDAE) was used to assess pre- and postoperative language functions; visual object naming (DO 80) and semantic-association (Pyramid and Palm Tree Test, PPTT) tests assessed intraoperative linguistic performance. DO 80 and PPTT were performed alternatively during subcortical functional monitoring while performing tumor resection and sfBDAE was assessed 1-week postoperatively. Most patients with observed language impairment during awake surgery showed improved language function postoperatively. Both intraoperative DO 80 and PPTT showed significant correlation to postoperative sfBDAE domain scores (p < 0.05), with a higher correlation observed with PPTT. A linear regression model showed that only PPTT predicted the postoperative sfBDAE domain scores with the adjusted R 2 ranging from 0.51 to 0.89 (all p < 0.01). Receiver operating characteristic analysis showed a cutoff value of PPTT that yielded a sensitivity of 80% and specificity of 100%. PPTT may be a feasible tool for intraoperative linguistic evaluation that can predict postoperative language outcomes. Further studies are needed to determine the extent of tumor resection that optimizes the postoperative language following neuroplasticity.

Fast ForWord®: the birth of the neurocognitive training revolution.

PubMed

Tallal, Paula

2013-01-01

In 1996, I cofounded Scientific Learning Corporation (SLC) with Drs Michael Merzenich, William Jenkins, and Steve Miller. I coined the term "Cogniceutical" to describe the new type of company we envisioned. SLC was the first company cofounded by academic scientists with the mission of building neurocognitive interventions. Fast ForWord® is the registered trade name of the platform SLC built to translate basic neuroplasticity-based training research into clinical and educational products. Fast ForWord® was the first cognitive neurotherapeutic intervention, the first to be individually adaptive in real time, the first "brain fitness" program that collected data over the Internet, and the first to use computer gaming technologies to change brains and enhance human potential. We included lofty goals in our first business plan for SLC. These included: using neuroplasticity-based training to improve language, literacy, and other academic skills; helping seniors maintain and recover function; helping people learn English as a second language; helping patient populations with neurological or mental disorders. SLC's first focus became improving language and literacy. Mike, Bill, Steve, and I began this journey together in 1994 with a laboratory-based research study that included seven children. To date, over two million children in 46 countries have used Fast ForWord® products. On any given school day, approximately 60,000 children log in to train on 1 of 10 Fast ForWord Language, Literacy, or Reading programs. We did not know at the time that we were creating what became a "disruptive innovation." This chapter chronicles this transformational journey. © 2013 Elsevier B.V. All rights reserved.

Differential patterns of functional and structural plasticity within and between inferior frontal gyri support training-induced improvements in inhibitory control proficiency.

PubMed

Chavan, Camille F; Mouthon, Michael; Draganski, Bogdan; van der Zwaag, Wietske; Spierer, Lucas

2015-07-01

Ample evidence indicates that inhibitory control (IC), a key executive component referring to the ability to suppress cognitive or motor processes, relies on a right-lateralized fronto-basal brain network. However, whether and how IC can be improved with training and the underlying neuroplastic mechanisms remains largely unresolved. We used functional and structural magnetic resonance imaging to measure the effects of 2 weeks of training with a Go/NoGo task specifically designed to improve frontal top-down IC mechanisms. The training-induced behavioral improvements were accompanied by a decrease in neural activity to inhibition trials within the right pars opercularis and triangularis, and in the left pars orbitalis of the inferior frontal gyri. Analyses of changes in brain anatomy induced by the IC training revealed increases in grey matter volume in the right pars orbitalis and modulations of white matter microstructure in the right pars triangularis. The task-specificity of the effects of training was confirmed by an absence of change in neural activity to a control working memory task. Our combined anatomical and functional findings indicate that differential patterns of functional and structural plasticity between and within inferior frontal gyri enhanced the speed of top-down inhibition processes and in turn IC proficiency. The results suggest that training-based interventions might help overcoming the anatomic and functional deficits of inferior frontal gyri manifesting in inhibition-related clinical conditions. More generally, we demonstrate how multimodal neuroimaging investigations of training-induced neuroplasticity enable revealing novel anatomo-functional dissociations within frontal executive brain networks. © 2015 Wiley Periodicals, Inc.

Skill-Specific Changes in Somatosensory Nogo Potentials in Baseball Players.

PubMed

Yamashiro, Koya; Sato, Daisuke; Onishi, Hideaki; Sugawara, Kazuhiro; Nakazawa, Sho; Shimojo, Hirofumi; Akatsuka, Kosuke; Nakata, Hiroki; Maruyama, Atsuo

2015-01-01

Athletic training is known to induce neuroplastic alterations in specific somatosensory circuits, which are reflected by changes in somatosensory evoked potentials and event-related potentials. The aim of this study was to clarify whether specific athletic training also affects somatosensory Nogo potentials related to the inhibition of movements. The Nogo potentials were recorded at nine cortical electrode positions (Fz, Cz, Pz, F3, F4, C3, C4, P3 and P4) in 12 baseball players (baseball group) and in 12 athletes in sports, such as track and field events and swimming, that do not require response inhibition, such as batting for training or performance (sports group). The Nogo potentials and Go/Nogo reaction times (Go/Nogo RTs) were measured under a somatosensory Go/Nogo paradigm in which subjects were instructed to rapidly push a button in response to stimulus presentation. The Nogo potentials were obtained by subtracting the Go trial from the Nogo trial. The peak Nogo-N2 was significantly shorter in the baseball group than that in the sports group. In addition, the amplitude of Nogo-N2 in the frontal area was significantly larger in the baseball group than that in the sports group. There was a significant positive correlation between the latency of Nogo-N2 and Go/Nogo RT. Moreover, there were significant correlations between the Go/Nogo RT and both the amplitude of Nogo-N2 and Nogo-P3 (i.e., amplitude of the Nogo-potentials increases with shorter RT). Specific athletic training regimens may induce neuroplastic alterations in sensorimotor inhibitory processes.

Effects of acute restraint-induced stress on glucocorticoid receptors and brain-derived neurotrophic factor after mild traumatic brain injury.

PubMed

Griesbach, G S; Vincelli, J; Tio, D L; Hovda, D A

2012-05-17

We have previously reported that experimental mild traumatic brain injury results in increased sensitivity to stressful events during the first post-injury weeks, as determined by analyzing the hypothalamic-pituitary-adrenal (HPA) axis regulation following restraint-induced stress. This is the same time period when rehabilitative exercise has proven to be ineffective after a mild fluid-percussion injury (FPI). Here we evaluated effects of stress on neuroplasticity. Adult male rats underwent either an FPI or sham injury. Additional rats were only exposed to anesthesia. Rats were exposed to 30 min of restraint stress, followed by tail vein blood collection at post-injury days (PID) 1, 7, and 14. The response to dexamethasone (DEX) was also evaluated. Hippocampal tissue was collected 120 min after stress onset. Brain-derived neurotrophic factor (BDNF) along with glucocorticoid (GR) and mineralocorticoid (MR) receptors was determined by Western blot analysis. Results indicated injury-dependent changes in glucocorticoid and mineralocorticoid receptors that were influenced by the presence of dexamethasone. Control and FPI rats responded differentially to DEX in that GR increases after receiving the lower dose of DEX were longer lasting in the FPI group. A suppression of MR was found at PID 1 in vehicle-treated FPI and Sham groups. Decreases in the precursor form of BDNF were observed in different FPI groups at PIDs 7 and 14. These findings suggest that the increased sensitivity to stressful events during the first post-injury weeks, after a mild FPI, has an impact on hippocampal neuroplasticity. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Methamphetamine addiction: involvement of CREB and neuroinflammatory signaling pathways

PubMed Central

Krasnova, Irina N.; Justinova, Zuzana; Cadet, Jean Lud

2017-01-01

Rationale and objectives Addiction to psychostimulant methamphetamine (METH) remains a major public health problem in the world. Animal models that use METH self-administration incorporate many features of human drug-taking behavior and are very helpful in elucidating mechanisms underlying METH addiction. These models are also helping to decipher the neurobiological substrates of associated neuropsychiatric complications. This review summarizes our work on the influence of METH self-administration on dopamine systems, transcriptional and immune responses in the brain. Methods We used the rat model of METH self-administration with extended access (15 hours/day for 8 consecutive days) to investigate the effects of voluntary METH intake on the markers of dopamine system integrity and changes in gene expression observed in the brain at 2 hours – 1 month after cessation of drug exposure. Results Extended access to METH self-administration caused changes in the rat brain that are consistent with clinical findings reported in neuroimaging and post-mortem studies of human METH addicts. In addition, gene expression studies using striatal tissues from METH self-administering rats revealed increased expression of genes involved in CREB signaling pathway and in the activation of neuroinflammatory response in the brain. Conclusion These data show an association of METH exposure with activation of neuroplastic and neuroinflammatory cascades in the brain. The neuroplastic changes may be involved in promoting METH addiction. Neuroinflammatory processes in the striatum may underlie cognitive deficits, depression, and parkinsonism reported in METH addicts. Therapeutic approaches that include suppression of neuroinflammation may be beneficial to addicted patients. PMID:26873080

Monocular deprivation of Fourier phase information boosts the deprived eye's dominance during interocular competition but not interocular phase combination.

PubMed

Bai, Jianying; Dong, Xue; He, Sheng; Bao, Min

2017-06-03

Ocular dominance has been extensively studied, often with the goal to understand neuroplasticity, which is a key characteristic within the critical period. Recent work on monocular deprivation, however, demonstrates residual neuroplasticity in the adult visual cortex. After deprivation of patterned inputs by monocular patching, the patched eye becomes more dominant. Since patching blocks both the Fourier amplitude and phase information of the input image, it remains unclear whether deprivation of the Fourier phase information alone is able to reshape eye dominance. Here, for the first time, we show that removing of the phase regularity without changing the amplitude spectra of the input image induced a shift of eye dominance toward the deprived eye, but only if the eye dominance was measured with a binocular rivalry task rather than an interocular phase combination task. These different results indicate that the two measurements are supported by different mechanisms. Phase integration requires the fusion of monocular images. The fused percept highly relies on the weights of the phase-sensitive monocular neurons that respond to the two monocular images. However, binocular rivalry reflects the result of direct interocular competition that strongly weights the contour information transmitted along each monocular pathway. Monocular phase deprivation may not change the weights in the integration (fusion) mechanism much, but alters the balance in the rivalry (competition) mechanism. Our work suggests that ocular dominance plasticity may occur at different stages of visual processing, and that homeostatic compensation also occurs for the lack of phase regularity in natural scenes. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Burning Eye Syndrome: Do Neuropathic Pain Mechanisms Underlie Chronic Dry Eye?

PubMed

Kalangara, Jerry P; Galor, Anat; Levitt, Roy C; Felix, Elizabeth R; Alegret, Ramon; Sarantopoulos, Constantine D

2016-04-01

Dry eye is a multi-factorial disorder that manifests with painful ocular symptoms and visual disturbances, which can only be partly attributed to tear dysfunction. This disorder may also involve neuroplasticity in response to neuronal injury. This review will emphasize the key characteristics of dry eye pain and its pathologic mechanisms, making the argument that a subset of dry eye represents a neuropathic pain disorder of the eye, more appropriately called "burning eye syndrome." A literature review was conducted using a PubMed search focusing on dry eye, corneal nociception, and neuropathic pain. Articles were reviewed and those discussing clinical course, pathophysiology, and neuronal regulation of chronic ocular pain as related to dry eye were summarized. We found that there is a discordance between ocular pain and dryness on the ocular surface. Although tear dysfunction may be one of the initial insults, its persistence may be associated with repeated ocular sensory nerve injury leading to an acute-to-chronic pain transition associated with neuropathologic changes (peripheral and central sensitization), neuronal dysfunction, and spontaneous ocular pain. Dry eye is becoming a major health concern due to its increasing incidence, significant morbidity, and economic burden. Recent evidence suggests that a subset of dry eye may be better represented as a chronic neuropathic pain disorder due to its features of dysesthesia, spontaneous pain, allodynia, and hyperalgesia. Future therapies targeted at the underlying neuroplasticity may yield improved efficacy for patients with this subset of dry eye, which we term "burning eye syndrome." © 2015 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Digital media, the developing brain and the interpretive plasticity of neuroplasticity.

PubMed

Choudhury, Suparna; McKinney, Kelly A

2013-04-01

The use and misuse of digital technologies among adolescents has been the focus of fiery debates among parents, educators, policy-makers and in the media. Recently, these debates have become shaped by emerging data from cognitive neuroscience on the development of the adolescent brain and cognition. "Neuroplasticity" has functioned as a powerful metaphor in arguments both for and against the pervasiveness of digital media cultures that increasingly characterize teenage life. In this paper, we propose that the debates concerning adolescents are the meeting point of two major social anxieties both of which are characterized by the threat of "abnormal" (social) behaviour: existing moral panics about adolescent behaviour in general and the growing alarm about intense, addictive, and widespread media consumption in modern societies. Neuroscience supports these fears but the same kinds of evidence are used to challenge these fears and reframe them in positive terms. Here, we analyze discourses about digital media, the Internet, and the adolescent brain in the scientific and lay literature. We argue that while the evidential basis is thin and ambiguous, it has immense social influence. We conclude by suggesting how we might move beyond the poles of neuro-alarmism and neuro-enthusiasm. By analyzing the neurological adolescent in the digital age as a socially extended mind, firstly, in the sense that adolescent cognition is distributed across the brain, body, and digital media tools and secondly, by viewing adolescent cognition as enabled and transformed by the institution of neuroscience, we aim to displace the normative terms of current debates.

Therapeutic effects of an anti-gravity locomotor training (AlterG) on postural balance and cerebellum structure in children with Cerebral Palsy.

PubMed

Rasooli, A H; Birgani, P M; Azizi, Sh; Shahrokhi, A; Mirbagheri, M M

2017-07-01

We evaluated the therapeutic effects of anti-gravity locomotor treadmill (AlterG) training on postural stability in children with Cerebral Palsy (CP) and spasticity, particularly in the lower extremity. AlterG can facilitate walking by reducing the weight of CP children by up to 80%; it can also help subjects maintain an appropriate posture during the locomotor AlterG training. Thus, we hypothesized that AlterG training, for a sufficient period of time, has a potential to produce cerebellum neuroplasticity, and consequently result in an effective permanent postural stability. AlterG training was given for 45 minutes, three times a week for two months. Postural balance was evaluated using posturography. The parameters of the Romberg based posturography were extracted to quantify the Center of Balance (CoP). The neuroplasticity of Cerebellum was evaluated using a Diffusion Tensor Imaging (DTI). The evaluations were done pre- and post-training. The Fractional Anisotropy (FA) feature was used for quantifying structural changes in the cerebellum. The results showed that AlterG training resulted in an increase in average FA value of the cerebellum white matter following the training. The results of the posturography evaluations showed a consistent improvement in postural stability. These results were consistent in all subjects. Our findings indicated that the improvement in the posture was accompanied with the enhancement of the cerebellum white matter structure. The clinical implication is that AlterG training can be considered a therapeutic tool for an effective and permanent improvement of postural stability in CP children.

Does vigorous exercise have a neuroprotective effect in Parkinson disease?

PubMed Central

2011-01-01

Parkinson disease (PD) is progressive, with dementia and medication-refractory motor problems common reasons for late-stage nursing-home placement. Increasing evidence suggests that ongoing vigorous exercise/physical fitness may favorably influence this progression. Parkinsonian animal models reveal exercise-related protection from dopaminergic neurotoxins, apparently mediated by brain neurotrophic factors and neuroplasticity (predicted from in vitro studies). Similarly, exercise consistently improves cognition in animals, also linked to enhanced neuroplasticity and increased neurotrophic factor expression. In these animal models, immobilization has the opposite effect. Brain-derived neurotrophic factor (BDNF) may mediate at least some of this exercise benefit. In humans, exercise increases serum BDNF, and this is known to cross the blood–brain barrier. PD risk in humans is significantly reduced by midlife exercise, documented in large prospective studies. No studies have addressed whether exercise influences dementia risk in PD, but exercised patients with PD improve cognitive scores. Among seniors in general, exercise or physical fitness has not only been associated with better cognitive scores, but midlife exercise significantly reduces the later risk of both dementia and mild cognitive impairment. Finally, numerous studies in seniors with and without dementia have reported increased cerebral gray matter volumes associated with physical fitness or exercise. These findings have several implications for PD clinicians. 1) Ongoing vigorous exercise and physical fitness should be highly encouraged. 2) PD physical therapy programs should include structured, graduated fitness instruction and guidance for deconditioned patients with PD. 3) Levodopa and other forms of dopamine replenishment therapy should be utilized to achieve the maximum capability and motivation for patients to maintain fitness. PMID:21768599

Evidence for Neuroplastic Compensation in the Cerebral Cortex of Persons with Depressive Illness

PubMed Central

Bansal, Ravi; Hellerstein, David J.; Peterson, Bradley S.

2017-01-01

We yoked anatomical brain Magnetic Resonance Imaging to a randomized, double-blind, placebo-controlled trial (RCT) of antidepressant medication for 10-week’s duration in patients with dysthymia. The RCT study design mitigated ascertainment bias by randomizing patients to receive either duloxetine or placebo, and it supported true causal inferences about treatment effects on the brain by controlling treatment assignment experimentally. We acquired 121 anatomical scans: at baseline and endpoint in 41 patients, and once in 39 healthy controls. At baseline, patients had diffusely thicker cortices than did healthy participants, and patients who had thicker cortices had proportionately less severe symptoms. During the trial, symptoms improved significantly more in medication- compared with placebo-treated patients; concurrently, thicknesses in medication-treated patients declined toward values in healthy controls, but they increased slightly, away from control values, in placebo-treated patients. Changes in symptom severity during the trial mediated the association of treatment assignment with the change in thickness, suggesting that the beneficial effects of medication on symptom severity were at least partially responsible for normalizing cortical thickness. Together our findings suggest that baseline cortical hypertrophy in medication-free patients likely represented a compensatory, neuroplastic response that attenuated symptom severity. Medication then reduced symptoms and lessened the need for compensation, thereby normalizing thickness. This is to the best of our knowledge the first study to report within an RCT a differential change in cortical morphology during medication treatment for depressive illness and the first to provide within an RCT in vivo evidence for the presence of neuroanatomical plasticity in humans. PMID:28265119

Intensive comprehensive aphasia programs: an international survey of practice.

PubMed

Rose, Miranda L; Cherney, Leora R; Worrall, Linda E

2013-01-01

In response to the need to simultaneously address multiple domains of the International Classification of Functioning, Disability and Health (ICF) in aphasia therapy and to incorporate intensive treatment doses consistent with principles of neuroplasticity, a potentially potent treatment option termed intensive comprehensive aphasia programs (ICAPs) has been developed. To conduct an international survey of ICAPs to determine the extent of their use and to explore current ICAP practices. A 32-item online survey was distributed internationally through Survey Monkey between May and August 2012. The survey addressed ICAP staffing, philosophy, values, funding, admission criteria, activities, family involvement, outcome measures, and factors considered important to success. Twelve ICAPs responded: 8 from the United States, 2 from Canada, and 1 each from Australia and the United Kingdom. The majority of ICAPs are affiliated with university programs and are funded through participant self-pay. ICAPs emphasize individualized treatment goals and evidence-based practices, with a focus on applying the principles of neuroplasticity related to repetition and intensity of treatment. On average, 6 people with aphasia attend each ICAP, for 4 days per week for 4 weeks, receiving about 100 hours of individual, group, and computer-based treatment. Speech-language pathologists, students, and volunteers staff the majority of ICAPs. ICAPs are increasing in number but remain a rare service delivery option. They address the needs of individuals who want access to intensive treatment and are interested in making significant changes to their communication skills and psychosocial well-being in a short period of time. Their efficacy and cost-effectiveness require future investigation.

Role of DOR in neuronal plasticity changes promoted by food-seeking behaviour.

PubMed

Mancino, Samantha; Mendonça-Netto, Sueli; Martín-García, Elena; Maldonado, Rafael

2017-09-01

Several lines of evidence support that food overconsumption may be related to the role of the endogenous opioid system in the control of food palatability. The opioid system, and particularly the delta opioid receptor (DOR), plays a crucial role in the regulation of food rewarding properties. In our study, we used operant conditioning maintained by chocolate-flavoured pellets to investigate the role of DOR in the motivation for palatable food and the structural plasticity changes promoted by this behaviour. For this purpose, we evaluated the specific role of this receptor in the behavioural and neuroplastic changes induced by palatable food in the prefrontal cortex (PFC), hippocampus (HCP) and nucleus accumbens (NAc) in constitutive knockout (KO) mice deficient in DOR. Mutant mice and their wild-type littermates were trained to obtain chocolate-flavoured pellets on fixed ratio 1 (FR1), FR5 and progressive ratio (PR) schedule of reinforcement. No significant differences between genotypes were revealed on operant behaviour acquisition in FR1. DOR knockout mice displayed lower number of active lever-presses than wild-type mice on FR5, and a similar decrease was revealed in DOR KO mice in the breaking point during the PR. This operant training to obtain palatable food increased dendritic spine density in the PFC, HCP and NAc shell of wild-type, but these plasticity changes were abolished in DOR KO mice. Our results support the hypothesis that DOR regulates the reinforcing effects and motivation for palatable food through neuroplastic changes in specific brain reward areas. © 2016 Society for the Study of Addiction.

A Review of Transcranial Magnetic Stimulation and Multimodal Neuroimaging to Characterize Post-Stroke Neuroplasticity

PubMed Central

Auriat, Angela M.; Neva, Jason L.; Peters, Sue; Ferris, Jennifer K.; Boyd, Lara A.

2015-01-01

Following stroke, the brain undergoes various stages of recovery where the central nervous system can reorganize neural circuitry (neuroplasticity) both spontaneously and with the aid of behavioral rehabilitation and non-invasive brain stimulation. Multiple neuroimaging techniques can characterize common structural and functional stroke-related deficits, and importantly, help predict recovery of function. Diffusion tensor imaging (DTI) typically reveals increased overall diffusivity throughout the brain following stroke, and is capable of indexing the extent of white matter damage. Magnetic resonance spectroscopy (MRS) provides an index of metabolic changes in surviving neural tissue after stroke, serving as a marker of brain function. The neural correlates of altered brain activity after stroke have been demonstrated by abnormal activation of sensorimotor cortices during task performance, and at rest, using functional magnetic resonance imaging (fMRI). Electroencephalography (EEG) has been used to characterize motor dysfunction in terms of increased cortical amplitude in the sensorimotor regions when performing upper limb movement, indicating abnormally increased cognitive effort and planning in individuals with stroke. Transcranial magnetic stimulation (TMS) work reveals changes in ipsilesional and contralesional cortical excitability in the sensorimotor cortices. The severity of motor deficits indexed using TMS has been linked to the magnitude of activity imbalance between the sensorimotor cortices. In this paper, we will provide a narrative review of data from studies utilizing DTI, MRS, fMRI, EEG, and brain stimulation techniques focusing on TMS and its combination with uni- and multimodal neuroimaging methods to assess recovery after stroke. Approaches that delineate the best measures with which to predict or positively alter outcomes will be highlighted. PMID:26579069

Functional brain activation associated with working memory training and transfer.

PubMed

Clark, Cameron M; Lawlor-Savage, Linette; Goghari, Vina M

2017-09-15

While behavioural trials of working memory (WM) training have received much attention in recent years, a lesser explored parallel approach is functional neuroimaging. A small literature has suggested a complex time course for functional activation pattern changes following WM training (i.e. not simply increasing or decreasing due to training); however, no study to date has examined such neuroplastic effects in both the training task (dual n-back) and the fluid intelligence transfer task to which the training is purported to transfer (Raven's Matrices). This study investigated neural correlates of WM training in healthy young adults randomized to six weeks of WM training, or an active control condition (processing speed training) with a pre- and post-training fMRI design. Results indicated significant reductions in activation for the WM trained group in key WM-task related areas for trained WM tasks after training compared to the processing speed active control group. The same pattern of training related decreases in activation for the WM trained group was not observed for the transfer task, which is consistent with null results for all cognitive outcomes of the present trial. The observed pattern of results suggests that repetitive practice with a complex task does indeed lead to neuroplastic processes that very likely represent the reduced demand for attentional control while sub-components of the task become more routinized with practice. We suggest that future research investigate neural correlates of WM training in populations for which WM itself is impaired and/or behavioural trials of WM training have returned more promising results. Copyright © 2017 Elsevier B.V. All rights reserved.

BDNF and VEGF in the pathogenesis of stress-induced affective diseases: an insight from experimental studies.

PubMed

Nowacka, Marta; Obuchowicz, Ewa

2013-01-01

Stress is known to play an important role in etiology, development and progression of affective diseases. Especially, chronic stress, by initiating changes in the hypothalamic-pituitary-adrenal axis (HPA), neurotransmission and the immune system, acts as a trigger for affective diseases. It has been reported that the rise in the concentration of pro-inflammatory cytokines and persistent up-regulation of glucocorticoid expression in the brain and periphery increases the excitotoxic effect on CA3 pyramidal neurons in the hippocampus resulting in dendritic atrophy, apoptosis of neurons and possibly inhibition of neurogenesis in adult brain. Stress was observed to disrupt neuroplasticity in the brain, and growing evidence demonstrates its role in the pathomechanism of affective disorders. Experimental studies indicate that a well-known brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) which have recently focused increasing attention of neuroscientists, promote cell survival, positively modulate neuroplasticity and hippocampal neurogenesis. In this paper, we review the alterations in BDNF and VEGF pathways induced by chronic and acute stress, and their relationships with HPA axis activity. Moreover, behavioral effects evoked in rodents by both above-mentioned factors and the effects consequent to their deficit are presented. Biochemical as well as behavioral findings suggest that BDNF and VEGF play an important role as components of cascade of changes in the pathomechanism of stress-induced affective diseases. Further studies on the mechanisms regulating their expression in stress conditions are needed to better understand the significance of trophic hypothesis of stress-induced affective diseases.

Is non-invasive neuromuscular electrical stimulation effective in severe chronic neurogenic dysphagia? Reporton a post-traumatic brain injury patient.

PubMed

Calabrò, Rocco Salvatore; Nibali, Valeria Conti; Naro, Antonino; Floridia, Daniela; Pizzimenti, Maria; Salmeri, Lucia; Salviera, Carlo; Bramanti, Placido

2016-01-01

Neurogenic dysphagia is a difficulty in swallowing induced by nervous system disease. It often causes serious complications, which are preventable if dysphagia is properly managed. There is growing debate concerning the usefulness of non-invasive neuromuscular electrical stimulation (NMES) in treating swallowing dysfunction. Aim of this study was to assess the effectiveness of Vitalstim© device, and to investigate the neurophysiological mechanisms underlying functional recovery. A 34-year-old man, affected by severe chronic dysphagia following traumatic brain injury, underwent two different intensive rehabilitation trainings, including either conventional rehabilitation alone or coupled to Vitalstim training. We evaluated patient swallowing function in two separate sessions (i.e. before and after the two trainings) by means of ad hoc swallowing function scales and electrophysiological parameters (rapid paired associative stimulation). The overall Vitalstim program was articulated in 6 weekly sessions for 6 weeks. The patient did not report any side-effect either during or following both the intensive rehabilitation trainings. We observed an important improvement in swallowing function only after Vitalstim training. In fact, the patient was eventually able to safely eat even solid food. This is the first report objectively suggesting (by means of rPAS) a correlation between the brain neuroplastic changes induced by Vitalstim and the swallowing function improvement. It is hypothesizable that Vitalstim may have targeted cortical (and maybe subcortical) brain areas that are recruited during the highly coordinated function of swallowing, and it may have thus potentiated the well-known neuroplastic changes induced by repetitive and intensive swallowing exercises, probably thanks to metaplasticity phenomena.

Strength and Aerobic Exercises Improve Spatial Memory in Aging Rats Through Stimulating Distinct Neuroplasticity Mechanisms.

PubMed

Vilela, Thais Ceresér; Muller, Alexandre Pastoris; Damiani, Adriani Paganini; Macan, Tamires Pavei; da Silva, Sabrina; Canteiro, Paula Bortoluzzi; de Sena Casagrande, Alisson; Pedroso, Giulia Dos Santos; Nesi, Renata Tiscoski; de Andrade, Vanessa Moraes; de Pinho, Ricardo Aurino

2017-12-01

Aging is associated with impaired cognition and memory and increased susceptibility to neurodegenerative disorders. Physical exercise is neuroprotective; however, the major evidence of this effect involves studies of only aerobic training in young animals. The benefits of other exercise protocols such as strength training in aged animals remains unknown. Here, we investigated the effect of aerobic and strength training on spatial memory and hippocampal plasticity in aging rats. Aging Wistar rats performed aerobic or strength training for 50 min 3 to 4 days/week for 8 weeks. Spatial memory and neurotrophic and glutamatergic signaling in the hippocampus of aged rats were evaluated after aerobic or strength training. Both aerobic and strength training improved cognition during the performance of a spatial memory task. Remarkably, the improvement in spatial memory was accompanied by an increase in synaptic plasticity proteins within the hippocampus after exercise training, with some differences in the intracellular functions of those proteins between the two exercise protocols. Moreover, neurotrophic signaling (CREB, BDNF, and the P75 NTR receptor) increased after training for both exercise protocols, and aerobic exercise specifically increased glutamatergic proteins (NMDA receptor and PSD-95). We also observed a decrease in DNA damage after aerobic training. In contrast, strength training increased levels of PKCα and the proinflammatory factors TNF-α and IL-1β. Overall, our results show that both aerobic and strength training improved spatial memory in aging rats through inducing distinct molecular mechanisms of neuroplasticity. Our findings extend the idea that exercise protocols can be used to improve cognition during aging.

Effect of training on corticomotor excitability in clinical neck pain.

PubMed

Rittig-Rasmussen, B; Kasch, H; Fuglsang-Frederiksen, A; Svensson, P; Jensen, T S

2014-09-01

Corticomotor excitability has been shown to correlate with motor learning and functional recovery. The aim of the present study was to monitor changes in excitability of the corticomotor pathways induced by neck training and to compare the effects in patients with neck or knee pain and pain-free participants. Corticomotor excitability was assessed using transcranial magnetic stimulation and electromyography at baseline, after 30 min and 1 h, and at a 1-week follow-up visit. The primary outcome measures were changes in amplitudes and latencies of motor evoked potentials (MEPs) at 1-week follow-up. MEP responses induced by neck training yielded significantly different outcomes in the three groups. In the group with neck pain and training, MEP amplitudes were significantly reduced between baseline and 30 min (p ≤ 0.05), but with no significant difference between baseline, 1 h (p = 0.178) and 1 week (p = 0.067). In the group with knee pain and training, MEP amplitudes significantly increased between baseline and 30 min (p ≤ 0.01) and 1 h (p < 0.001), but not after 1 week (p = 0.524) compared with baseline. In the pain-free group, there were no changes over time. Neck training reduced neuroplastic responsiveness of corticomotor pathways in neck pain patients in contrast to knee pain patients and pain-free participants. Increased attention to adaptive and maladaptive neuroplastic responses induced by training may prove valuable in the process of optimizing clinical outcomes. © 2014 European Pain Federation - EFIC®

Brain neuroplastic changes accompany anxiety and memory deficits in a model of complex regional pain syndrome.

PubMed

Tajerian, Maral; Leu, David; Zou, Yani; Sahbaie, Peyman; Li, Wenwu; Khan, Hamda; Hsu, Vivian; Kingery, Wade; Huang, Ting Ting; Becerra, Lino; Clark, J David

2014-10-01

Complex regional pain syndrome (CRPS) is a painful condition with approximately 50,000 annual new cases in the United States. It is a major cause of work-related disability, chronic pain after limb fractures, and persistent pain after extremity surgery. Additionally, CRPS patients often experience cognitive changes, anxiety, and depression. The supraspinal mechanisms linked to these CRPS-related comorbidities remain poorly understood. The authors used a previously characterized mouse model of tibia fracture/cast immobilization showing the principal stigmata of CRPS (n = 8 to 20 per group) observed in humans. The central hypothesis was that fracture/cast mice manifest changes in measures of thigmotaxis (indicative of anxiety) and working memory reflected in neuroplastic changes in amygdala, perirhinal cortex, and hippocampus. The authors demonstrate that nociceptive sensitization in these mice is accompanied by altered thigmotactic behaviors in the zero maze but not open field assay, and working memory dysfunction in novel object recognition and social memory but not in novel location recognition. Furthermore, the authors found evidence of structural changes and synaptic plasticity including changes in dendritic architecture and decreased levels of synaptophysin and brain-derived neurotrophic factor in specific brain regions. The study findings provide novel observations regarding behavioral changes and brain plasticity in a mouse model of CRPS. In addition to elucidating some of the supraspinal correlates of the syndrome, this work supports the potential use of therapeutic interventions that not only directly target sensory input and other peripheral mechanisms, but also attempt to ameliorate the broader pain experience by modifying its associated cognitive and emotional comorbidities.

A mouse model for pain and neuroplastic changes associated with pancreatic ductal adenocarcinoma.

PubMed

Selvaraj, Deepitha; Hirth, Michael; Gandla, Jagadeesh; Kuner, Rohini

2017-08-01

Pancreatic ductal adenocarcinoma (PDAC) continues to be one of the deadliest human malignancies and is associated with excruciating pain, which is a serious complication and severely impacts the quality of life in patients. In human patients, poor survival prognosis is linked to remarkable remodeling of intrapancreatic nerves, which, in turn, is correlated to increased pain intensity. Understanding mechanisms underlying pain associated with PDAC has been hampered by the lack of animal models which replicate all germane aspects of the disease and importantly, enable analyses of pain associated with PDAC. In this study, we describe an immunocompetent orthotopic mouse model of PDAC involving intrapancreatic growth of K8484 mouse PDAC cells, which reliably exhibits a large number of key characteristics of human PDAC, including its unique histopathology and neuroplastic changes. We observed that tumor-bearing mice demonstrated significant abdominal mechanical hypersensitivity to von Frey stimuli as well as on-going pain in the conditioned place preference paradigm. Moreover, a myriad of other behavioral tests revealed that indicators of overall well-being were significantly reduced in tumor-bearing mice as compared to sham mice. Morphological and immunohistochemical analyses revealed structural remodeling in several different types of sensory and autonomic nerve fibers. Finally, perineural invasion of tumor cells, a cardinal manifestation in human PDAC, was also observed in our orthotopic mouse model. Thus, we describe a validated tumor model for quantitatively testing hypersensitivity and pain in PDAC, which lays a crucial basis for interrogating tumor-nerve interactions and the molecular and cellular mechanisms underlying pain in PDAC.

Non-cytotoxic Concentration of Cisplatin Decreases Neuroplasticity-Related Proteins and Neurite Outgrowth Without Affecting the Expression of NGF in PC12 Cells.

PubMed

Ferreira, Rafaela Scalco; Dos Santos, Neife Aparecida Guinaim; Martins, Nádia Maria; Fernandes, Laís Silva; Dos Santos, Antonio Cardozo

2016-11-01

Cisplatin is the most effective and neurotoxic platinum chemotherapeutic agent. It induces a peripheral neuropathy characterized by distal axonal degeneration that might progress to degeneration of cell bodies and apoptosis. Most symptoms occur nearby distal axonal branches and axonal degeneration might induce peripheral neuropathy regardless neuronal apoptosis. The toxic mechanism of cisplatin has been mainly associated with DNA damage, but cisplatin might also affect neurite outgrowth. Nevertheless, the neurotoxic mechanism of cisplatin remains unclear. We investigated the early effects of cisplatin on axonal plasticity by using non-cytotoxic concentrations of cisplatin and PC12 cells as a model of neurite outgrowth and differentiation. PC12 cells express NGF-receptors (trkA) and respond to NGF by forming neurites, branches and synaptic vesicles. For comparison, we used a neuronal model (SH-SY5Y cells) that does not express trkA nor responds to NGF. Cisplatin did not change NGF expression in PC12 cells and decreased neurite outgrowth in both models, suggesting a NGF/trkA independent mechanism. It also reduced axonal growth (GAP-43) and synaptic (synapsin I and synaptophysin) proteins in PC12 cells, without inducing mitochondrial damage or apoptosis. Therefore, cisplatin might affect axonal plasticity before DNA damage, NGF/trkA down-regulation, mitochondrial damage or neuronal apoptosis. This is the first study to show that neuroplasticity-related proteins might be early targets of the neurotoxic action of cisplatin and their role on cisplatin-induced peripheral neuropathy should be investigated in vivo.

Phosphoproteomics and Bioinformatics Analyses of Spinal Cord Proteins in Rats with Morphine Tolerance

PubMed Central

Liaw, Wen-Jinn; Tsao, Cheng-Ming; Huang, Go-Shine; Wu, Chin-Chen; Ho, Shung-Tai; Wang, Jhi-Joung; Tao, Yuan-Xiang; Shui, Hao-Ai

2014-01-01

Introduction Morphine is the most effective pain-relieving drug, but it can cause unwanted side effects. Direct neuraxial administration of morphine to spinal cord not only can provide effective, reliable pain relief but also can prevent the development of supraspinal side effects. However, repeated neuraxial administration of morphine may still lead to morphine tolerance. Methods To better understand the mechanism that causes morphine tolerance, we induced tolerance in rats at the spinal cord level by giving them twice-daily injections of morphine (20 µg/10 µL) for 4 days. We confirmed tolerance by measuring paw withdrawal latencies and maximal possible analgesic effect of morphine on day 5. We then carried out phosphoproteomic analysis to investigate the global phosphorylation of spinal proteins associated with morphine tolerance. Finally, pull-down assays were used to identify phosphorylated types and sites of 14-3-3 proteins, and bioinformatics was applied to predict biological networks impacted by the morphine-regulated proteins. Results Our proteomics data showed that repeated morphine treatment altered phosphorylation of 10 proteins in the spinal cord. Pull-down assays identified 2 serine/threonine phosphorylated sites in 14-3-3 proteins. Bioinformatics further revealed that morphine impacted on cytoskeletal reorganization, neuroplasticity, protein folding and modulation, signal transduction and biomolecular metabolism. Conclusions Repeated morphine administration may affect multiple biological networks by altering protein phosphorylation. These data may provide insight into the mechanism that underlies the development of morphine tolerance. PMID:24392096

Morphine Regulated Synaptic Networks Revealed by Integrated Proteomics and Network Analysis*

PubMed Central

Stockton, Steven D.; Gomes, Ivone; Liu, Tong; Moraje, Chandrakala; Hipólito, Lucia; Jones, Matthew R.; Ma'ayan, Avi; Morón, Jose A.; Li, Hong; Devi, Lakshmi A.

2015-01-01

Despite its efficacy, the use of morphine for the treatment of chronic pain remains limited because of the rapid development of tolerance, dependence and ultimately addiction. These undesired effects are thought to be because of alterations in synaptic transmission and neuroplasticity within the reward circuitry including the striatum. In this study we used subcellular fractionation and quantitative proteomics combined with computational approaches to investigate the morphine-induced protein profile changes at the striatal postsynaptic density. Over 2,600 proteins were identified by mass spectrometry analysis of subcellular fractions enriched in postsynaptic density associated proteins from saline or morphine-treated striata. Among these, the levels of 34 proteins were differentially altered in response to morphine. These include proteins involved in G-protein coupled receptor signaling, regulation of transcription and translation, chaperones, and protein degradation pathways. The altered expression levels of several of these proteins was validated by Western blotting analysis. Using Genes2Fans software suite we connected the differentially expressed proteins with proteins identified within the known background protein-protein interaction network. This led to the generation of a network consisting of 116 proteins with 40 significant intermediates. To validate this, we confirmed the presence of three proteins predicted to be significant intermediates: caspase-3, receptor-interacting serine/threonine protein kinase 3 and NEDD4 (an E3-ubiquitin ligase identified as a neural precursor cell expressed developmentally down-regulated protein 4). Because this morphine-regulated network predicted alterations in proteasomal degradation, we examined the global ubiquitination state of postsynaptic density proteins and found it to be substantially altered. Together, these findings suggest a role for protein degradation and for the ubiquitin/proteasomal system in the etiology of opiate dependence and addiction. PMID:26149443

Application of neuroscience to technology in stroke rehabilitation.

PubMed

Burns, Martha S

2008-01-01

The past decade has seen remarkable advances in our understanding of mechanisms that drive functional neuroplastic change after brain injury and the mirror neuron system that appears essential for language learning and communicative interaction. This article describes five neuroscience-based interventions available for clinical practice, with a discussion of the potential value of mirror neurons in stroke rehabilitation. Case-study data on three adults with aphasia who received various combinations of neuroscience-derived technological interventions are provided to inform the clinician of the potential advantages of technology as an adjunct to, not a substitution for, conventional therapeutic intervention.

Mechanisms of, and Adjuvants for, Bone Pain.

PubMed

Figura, Nicholas; Smith, Joshua; Yu, Hsiang-Hsuan Michael

2018-06-01

Metastatic bone pain is a complex, poorly understood process. Understanding the unique mechanisms causing cancer-induced bone pain may lead to potential therapeutic targets. This article discusses the effects of osteoclast overstimulation within the tumor microenvironment; the role of inflammatory factors at the tumor-nociceptor interface; the development of structural instability, causing mechanical nerve damage; and, ultimately, the neuroplastic changes in the setting of sustained pain. Several adjuvant therapies are available to attenuate metastatic bone pain. This article discusses the role of pharmacologic therapies, surgery, kyphoplasty, vertebroplasty, and radiofrequency ablation. Copyright © 2018 Elsevier Inc. All rights reserved.

[Morphologic changes during neuroplastic nerve restoration].

PubMed

Bakalski, E P; Rozhkov, E N

1976-06-01

The dynamics of ultrastructural changes in plastic recovery of the function of the additional nerve by the anterior branch of the second cervical nerve was studied. The nerve cells at the level of the donor-nerve were found to be highly reactive and plastic. It was established that in the process of heterogenic regeneration of the nerve the most substantial changes in neuronal structures were observed during the first two months. The cysterns of the endoplasmic network remained dilated for a long time after platic operation with might be related with the increased protein metabolism in the neuron.

How synapses can enhance sensibility of a neural network

NASA Astrophysics Data System (ADS)

Protachevicz, P. R.; Borges, F. S.; Iarosz, K. C.; Caldas, I. L.; Baptista, M. S.; Viana, R. L.; Lameu, E. L.; Macau, E. E. N.; Batista, A. M.

2018-02-01

In this work, we study the dynamic range in a neural network modelled by cellular automaton. We consider deterministic and non-deterministic rules to simulate electrical and chemical synapses. Chemical synapses have an intrinsic time-delay and are susceptible to parameter variations guided by learning Hebbian rules of behaviour. The learning rules are related to neuroplasticity that describes change to the neural connections in the brain. Our results show that chemical synapses can abruptly enhance sensibility of the neural network, a manifestation that can become even more predominant if learning rules of evolution are applied to the chemical synapses.

Stereoselective modulatory actions of oleamide on GABAA receptors and voltage-gated Na+ channels in vitro: a putative endogenous ligand for depressant drug sites in CNS

PubMed Central

Verdon, Bernard; Zheng, Jian; Nicholson, Russell A; Ganelli, C Robin; Lees, George

2000-01-01

cis-9,10-octadecenoamide (‘oleamide') accumulates in CSF on sleep deprivation. It induces sleep in animals (the trans form is inactive) but its cellular actions are poorly characterized. We have used electrophysiology in cultures from embryonic rat cortex and biochemical studies in mouse nerve preparations to address these issues. Twenty μM cis-oleamide (but not trans) reversibly enhanced GABAA currents and depressed the frequency of spontaneous excitatory and inhibitory synaptic activity in cultured networks. cis-oleamide stereoselectively blocked veratridine-induced (but not K+-induced) depolarisation of mouse synaptoneurosomes (IC50, 13.9 μM). The cis isomer stereoselectively blocked veratridine-induced (but not K+-induced) [3H]-GABA release from mouse synaptosomes (IC50, 4.6 μM). At 20 μM cis-oleamide, but not trans, produced a marked inhibition of Na+ channel-dependent rises in intrasynaptosomal Ca2+. The physiological significance of these observations was examined by isolating Na+ spikes in cultured pyramidal neurones. Sixty-four μM cis-oleamide did not significantly alter the amplitude, rate of rise or duration of unitary action potentials (1 Hz). cis-Oleamide stereoselectively suppressed sustained repetitive firing (SRF) in these cells with an EC50 of 4.1 μM suggesting a frequency- or state-dependent block of voltage-gated Na+ channels. Oleamide is a stereoselective modulator of both postsynaptic GABAA receptors and presynaptic or somatic voltage-gated Na+ channels which are crucial for synaptic inhibition and conduction. The modulatory actions are strikingly similar to those displayed by sedative or anticonvulsant barbiturates and a variety of general anaesthetics. Oleamide may represent an endogenous modulator for drug receptors and an important regulator of arousal. PMID:10694234

Chloride channels as tools for developing selective insecticides.

PubMed

Bloomquist, Jeffrey R

2003-12-01

Ligand-gated chloride channels underlie inhibition in excitable membranes and are proven target sites for insecticides. The gamma-aminobutyric acid (GABA(1)) receptor/chloride ionophore complex is the primary site of action for a number of currently used insecticides, such as lindane, endosulfan, and fipronil. These compounds act as antagonists by stabilizing nonconducting conformations of the chloride channel. Blockage of the GABA-gated chloride channel reduces neuronal inhibition, which leads to hyperexcitation of the central nervous system, convulsions, and death. We recently investigated the mode of action of the silphinenes, plant-derived natural compounds that structurally resemble picrotoxinin. These materials antagonize the action of GABA on insect neurons and block GABA-mediated chloride uptake into mouse brain synaptoneurosomes in a noncompetitive manner. In mammals, avermectins have a blocking action on the GABA-gated chloride channel consistent with a coarse tremor, whereas at longer times and higher concentrations, activation of the channel suppresses neuronal activity. Invertebrates display ataxia, paralysis, and death as the predominant signs of poisoning, with a glutamate-gated chloride channel playing a major role. Additional target sites for the avermectins or other chloride channel-directed compounds might include receptors gated by histamine, serotonin, or acetylcholine.The voltage-sensitive chloride channels form another large gene family of chloride channels. Voltage-dependent chloride channels are involved in a number of physiological processes including: maintenance of electrical excitability, chloride ion secretion and resorption, intravesicular acidification, and cell volume regulation. A subset of these channels is affected by convulsants and insecticides in mammals, although the role they play in acute lethality in insects is unclear. Given the wide range of functions that they mediate, these channels are also potential targets for insecticide development. Copyright 2003 Wiley-Liss, Inc.

The disaggregation theory of signal transduction revisited: further evidence that G proteins are multimeric and disaggregate to monomers when activated.

PubMed

Jahangeer, S; Rodbell, M

1993-10-01

We have compared the sedimentation rates on sucrose gradients of the heterotrimeric GTP-binding regulatory (G) proteins Gs, G(o), Gi, and Gq extracted from rat brain synaptoneurosomes with Lubrol and digitonin. The individual alpha and beta subunits were monitored with specific antisera. In all cases, both subunits cosedimented, indicating that the subunits are likely complexed as heterotrimers. When extracted with Lubrol all of the G proteins sedimented with rates of about 4.5 S (consistent with heterotrimers) whereas digitonin extracted 60% of the G proteins with peaks at 11 S; 40% pelleted as larger structures. Digitonin-extracted Gi was cross-linked by p-phenylenedimaleimide, yielding structures too large to enter polyacrylamide gels. No cross-linking of Lubrol-extracted Gi occurred. Treatment of the membranes with guanosine 5'-[gamma-thio]triphosphate and Mg2+ yielded digitonin-extracted structures with peak sedimentation values of 8.5 S--i.e., comparable to that of purified G(o) in digitonin and considerably larger than the Lubrol-extracted 2S structures representing the separated alpha and beta gamma subunits formed by the actions of guanosine 5'-[gamma-thio]triphosphate. It is concluded that the multimeric structures of G proteins in brain membranes are at least partially preserved in digitonin and that activation of these structures in membranes yields monomers of G proteins rather than the disaggregated products (alpha and beta gamma complexes) observed in Lubrol. It is proposed that hormones and GTP affect the dynamic interplay between multimeric G proteins and receptors in a fashion analogous to the actions of ATP on the dynamic interactions between myosin and actin filaments. Signal transduction is mediated by activated monomers released from the multimers during the activation process.

The disaggregation theory of signal transduction revisited: further evidence that G proteins are multimeric and disaggregate to monomers when activated.

PubMed Central

Jahangeer, S; Rodbell, M

1993-01-01

We have compared the sedimentation rates on sucrose gradients of the heterotrimeric GTP-binding regulatory (G) proteins Gs, G(o), Gi, and Gq extracted from rat brain synaptoneurosomes with Lubrol and digitonin. The individual alpha and beta subunits were monitored with specific antisera. In all cases, both subunits cosedimented, indicating that the subunits are likely complexed as heterotrimers. When extracted with Lubrol all of the G proteins sedimented with rates of about 4.5 S (consistent with heterotrimers) whereas digitonin extracted 60% of the G proteins with peaks at 11 S; 40% pelleted as larger structures. Digitonin-extracted Gi was cross-linked by p-phenylenedimaleimide, yielding structures too large to enter polyacrylamide gels. No cross-linking of Lubrol-extracted Gi occurred. Treatment of the membranes with guanosine 5'-[gamma-thio]triphosphate and Mg2+ yielded digitonin-extracted structures with peak sedimentation values of 8.5 S--i.e., comparable to that of purified G(o) in digitonin and considerably larger than the Lubrol-extracted 2S structures representing the separated alpha and beta gamma subunits formed by the actions of guanosine 5'-[gamma-thio]triphosphate. It is concluded that the multimeric structures of G proteins in brain membranes are at least partially preserved in digitonin and that activation of these structures in membranes yields monomers of G proteins rather than the disaggregated products (alpha and beta gamma complexes) observed in Lubrol. It is proposed that hormones and GTP affect the dynamic interplay between multimeric G proteins and receptors in a fashion analogous to the actions of ATP on the dynamic interactions between myosin and actin filaments. Signal transduction is mediated by activated monomers released from the multimers during the activation process. Images Fig. 1 Fig. 2 PMID:8415607

Single-Molecule Imaging of PSD-95 mRNA Translation in Dendrites and Its Dysregulation in a Mouse Model of Fragile X Syndrome

PubMed Central

Ifrim, Marius F.; Williams, Kathryn R.

2015-01-01

Fragile X syndrome (FXS) is caused by the loss of the fragile X mental retardation protein (FMRP), an RNA binding protein that regulates translation of numerous target mRNAs, some of which are dendritically localized. Our previous biochemical studies using synaptoneurosomes demonstrate a role for FMRP and miR-125a in regulating the translation of PSD-95 mRNA. However, the local translation of PSD-95 mRNA within dendrites and spines, as well as the roles of FMRP or miR-125a, have not been directly studied. Herein, local synthesis of a Venus-PSD-95 fusion protein was directly visualized in dendrites and spines using single-molecule imaging of a diffusion-restricted Venus-PSD-95 reporter under control of the PSD-95 3′UTR. The basal translation rates of Venus-PSD-95 mRNA was increased in cultured hippocampal neurons from Fmr1 KO mice compared with WT neurons, which correlated with a transient elevation of endogenous PSD-95 within dendrites. Following mGluR stimulation with (S)-3,5-dihydroxyphenylglycine, the rate of Venus-PSD-95 mRNA translation increased rapidly in dendrites of WT hippocampal neurons, but not in those of Fmr1 KO neurons or when the binding site of miR125a, previously shown to bind PSD-95 3′UTR, was mutated. This study provides direct support for the hypothesis that local translation within dendrites and spines is dysregulated in FXS. Impairments in the regulated local synthesis of PSD-95, a critical regulator of synaptic structure and function, may affect the spatiotemporal control of PSD-95 levels and affect dendritic spine development and synaptic plasticity in FXS. PMID:25948262

Single-Molecule Imaging of PSD-95 mRNA Translation in Dendrites and Its Dysregulation in a Mouse Model of Fragile X Syndrome.

PubMed

Ifrim, Marius F; Williams, Kathryn R; Bassell, Gary J

2015-05-06

Fragile X syndrome (FXS) is caused by the loss of the fragile X mental retardation protein (FMRP), an RNA binding protein that regulates translation of numerous target mRNAs, some of which are dendritically localized. Our previous biochemical studies using synaptoneurosomes demonstrate a role for FMRP and miR-125a in regulating the translation of PSD-95 mRNA. However, the local translation of PSD-95 mRNA within dendrites and spines, as well as the roles of FMRP or miR-125a, have not been directly studied. Herein, local synthesis of a Venus-PSD-95 fusion protein was directly visualized in dendrites and spines using single-molecule imaging of a diffusion-restricted Venus-PSD-95 reporter under control of the PSD-95 3'UTR. The basal translation rates of Venus-PSD-95 mRNA was increased in cultured hippocampal neurons from Fmr1 KO mice compared with WT neurons, which correlated with a transient elevation of endogenous PSD-95 within dendrites. Following mGluR stimulation with (S)-3,5-dihydroxyphenylglycine, the rate of Venus-PSD-95 mRNA translation increased rapidly in dendrites of WT hippocampal neurons, but not in those of Fmr1 KO neurons or when the binding site of miR125a, previously shown to bind PSD-95 3'UTR, was mutated. This study provides direct support for the hypothesis that local translation within dendrites and spines is dysregulated in FXS. Impairments in the regulated local synthesis of PSD-95, a critical regulator of synaptic structure and function, may affect the spatiotemporal control of PSD-95 levels and affect dendritic spine development and synaptic plasticity in FXS. Copyright © 2015 the authors 0270-6474/15/357116-15$15.00/0.

Effect of D-cycloserine in conjunction with fear extinction training on extracellular signal-regulated kinase activation in medial prefrontal cortex and amygdala in rat

PubMed Central

Gupta, Subhash C.; Hillman, Brandon G.; Prakash, Anand; Ugale, Rajesh R; Stairs, Dustin J.; Dravid, Shashank M.

2013-01-01

D-cycloserine (DCS) is currently under clinical trials for a number of neuropsychiatric conditions and has been found to augment fear extinction in rodents and exposure therapy in humans. However, the molecular mechanism of DCS action in these multiple modalities remains unclear. Here, we describe the effect of DCS administration, alone or in conjunction with extinction training, on neuronal activity (c-fos) and neuronal plasticity (phospho-extracellular signal-regulated kinase, pERK) markers using immunohistochemistry. We found that intraperitoneal administration of DCS in untrained young rats (24–28 days old) increased c-fos and pERK-stained neurons in both the prelimbic (PL) and infralimbic (IL) division of the medial prefrontal cortex (mPFC) and reduced pERK levels in the lateral nucleus (CeL) of the central amygdala (CeA). Moreover, DCS administration significantly increased GluA1, GluN1, GluN2A, and GluN2B expression in mPFC. In a separate set of animals, we found that DCS facilitated fear extinction and increased pERK levels in IL, PL, intercalated cells and CeL, compared to saline control. In synaptoneurosomal preparation, we found that extinction training increased iGluR protein expression in the mPFC, compared to context animals. No significant difference in protein expression was observed between extinction-saline and extinction-DCS groups in the mPFC. In contrast, in the amygdala DCS in conjunction with extinction training led to an increase in iGluR subunit expression, compared to extinction-saline group. Our data suggest that the efficacy of DCS in neuropsychiatric disorders may be partly due to its ability to affect neuronal activity and signaling in the mPFC and amygdala subnuclei. PMID:23551217

Differential effects of natural rewards and pain on vesicular glutamate transporter expression in the nucleus accumbens.

PubMed

Tukey, David S; Lee, Michelle; Xu, Duo; Eberle, Sarah E; Goffer, Yossef; Manders, Toby R; Ziff, Edward B; Wang, Jing

2013-07-09

Pain and natural rewards such as food elicit different behavioral effects. Both pain and rewards, however, have been shown to alter synaptic activities in the nucleus accumbens (NAc), a key component of the brain reward system. Mechanisms by which external stimuli regulate plasticity at NAc synapses are largely unexplored. Medium spiny neurons (MSNs) from the NAc receive excitatory glutamatergic inputs and modulatory dopaminergic and cholinergic inputs from a variety of cortical and subcortical structures. Glutamate inputs to the NAc arise primarily from prefrontal cortex, thalamus, amygdala, and hippocampus, and different glutamate projections provide distinct synaptic and ultimately behavioral functions. The family of vesicular glutamate transporters (VGLUTs 1-3) plays a key role in the uploading of glutamate into synaptic vesicles. VGLUT1-3 isoforms have distinct expression patterns in the brain, but the effects of external stimuli on their expression patterns have not been studied. In this study, we use a sucrose self-administration paradigm for natural rewards, and spared nerve injury (SNI) model for chronic pain. We examine the levels of VGLUTs (1-3) in synaptoneurosomes of the NAc in these two behavioral models. We find that chronic pain leads to a decrease of VGLUT1, likely reflecting decreased projections from the cortex. Pain also decreases VGLUT3 levels, likely representing a decrease in projections from GABAergic, serotonergic, and/or cholinergic interneurons. In contrast, chronic consumption of sucrose increases VGLUT3 in the NAc, possibly reflecting an increase from these interneuron projections. Our study shows that natural rewards and pain have distinct effects on the VGLUT expression pattern in the NAc, indicating that glutamate inputs to the NAc are differentially modulated by rewards and pain.

Alterations in neuronal cytoskeletal and astrocytic proteins content in the brain of the autistic-like mouse strain C58/J.

PubMed

Barón-Mendoza, Isabel; García, Octavio; Calvo-Ochoa, Erika; Rebollar-García, Jorge Omar; Garzón-Cortés, Daniel; Haro, Reyes; González-Arenas, Aliesha

2018-06-06

Autism spectrum disorder (ASD) is a neurodevelopment disorder characterized by deficient social interaction, impaired communication as well as repetitive behaviors. ASD subjects present connectivity and neuroplasticity disturbances associated with morphological alterations in axons, dendrites, and dendritic spines. Given that the neuronal cytoskeleton and astrocytes have an essential role in regulating several mechanisms of neural plasticity, the aim of this work was to study alterations in the content of neuronal cytoskeletal components actin and tubulin and their associated proteins, as well as astrocytic proteins GFAP and TSP-1 in the brain of a C58/J mouse model of ASD. We determined the expression and regulatory phosphorylation state of cytoskeletal components in the prefrontal cortex, hippocampus, and cerebellum of C58/J mice by means of Western blotting. Our results show that autistic-like mice present: 1) region-dependent altered expression and phosphorylation patterns of Tau isoforms, associated with anomalous microtubule depolymerization; 2) reduced MAP2 A content in prefrontal cortex; 3) region-dependent changes in cofilin expression and phosphorylation, associated with abnormal actin filament depolymerizing dynamics; 4) diminished synaptopodin levels in the hippocampus; and 5) reduced content of the astrocyte-secreted protein TSP-1 in the prefrontal cortex and hippocampus. Our work demonstrates changes in the expression and phosphorylation of cytoskeletal proteins as well as in TSP-1 in the brain of the autistic-like mice C58/J, shedding light in one of the possible molecular mechanisms underpinning neuroplasticity alterations in the ASD brain and laying the foundation for future investigations in this topic. Copyright © 2018 Elsevier B.V. All rights reserved.

Acute and chronic craniofacial pain: brainstem mechanisms of nociceptive transmission and neuroplasticity, and their clinical correlates.

PubMed

Sessle, B J

2000-01-01

This paper reviews the recent advances in knowledge of brainstem mechanisms related to craniofacial pain. It also draws attention to their clinical implications, and concludes with a brief overview and suggestions for future research directions. It first describes the general organizational features of the trigeminal brainstem sensory nuclear complex (VBSNC), including its input and output properties and intrinsic characteristics that are commensurate with its strategic role as the major brainstem relay of many types of somatosensory information derived from the face and mouth. The VBSNC plays a crucial role in craniofacial nociceptive transmission, as evidenced by clinical, behavioral, morphological, and electrophysiological data that have been especially derived from studies of the relay of cutaneous nociceptive afferent inputs through the subnucleus caudalis of the VBSNC. The recent literature, however, indicates that some fundamental differences exist in the processing of cutaneous vs. other craniofacial nociceptive inputs to the VBSNC, and that rostral components of the VBSNC may also play important roles in some of these processes. Modulatory mechanisms are also highlighted, including the neurochemical substrate by which nociceptive transmission in the VBSNC can be modulated. In addition, the long-term consequences of peripheral injury and inflammation and, in particular, the neuroplastic changes that can be induced in the VBSNC are emphasized in view of the likely role that central sensitization, as well as peripheral sensitization, can play in acute and chronic pain. The recent findings also provide new insights into craniofacial pain behavior and are particularly relevant to many approaches currently in use for the management of pain and to the development of new diagnostic and therapeutic procedures aimed at manipulating peripheral inputs and central processes underlying nociceptive transmission and its control within the VBSNC.

Exercise benefits for the aging brain depend on the accompanying cognitive load: insights from sleep electroencephalogram.

PubMed

Horne, Jim

2013-11-01

Although exercise clearly offsets aging effects on the body, its benefits for the aging brain are likely to depend on the extent that physical activity (especially locomotion) facilitates multisensory encounters, curiosity, and interactions with novel environments; this is especially true for exploratory activity, which occupies much of wakefulness for most mammals in the wild. Cognition is inseparable from physical activity, with both interlinked to promote neuroplasticity and more successful brain aging. In these respects and for humans, exercising in a static, featureless, artificially lit indoor setting contrasts with exploratory outdoor walking within a novel environment during daylight. However, little is known about the comparative benefits for the aging brain of longer-term daily regimens of this latter nature including the role of sleep, to the extent that sleep enhances neuroplasticity as shown in short-term laboratory studies. More discerning analyses of sleep electroencephalogram (EEG) slow-wave activity especially 0.5-2-Hz activity would provide greater insights into use-dependent recovery processes during longer-term tracking of these regimens and complement slower changing waking neuropsychologic and resting functional magnetic resonance imaging (fMRI) measures, including those of the brain's default mode network. Although the limited research only points to ephemeral small sleep EEG effects of pure exercise, more enduring effects seem apparent when physical activity incorporates cognitive challenges. In terms of "use it or lose it," curiosity-driven "getting out and about," encountering, interacting with, and enjoying novel situations may well provide the brain with its real exercise, further reflected in changes to the dynamics of sleep. Copyright © 2013 Elsevier B.V. All rights reserved.

Stress Increases the Negative Effects of Chronic Pain on Hippocampal Neurogenesis.

PubMed

Romero-Grimaldi, Carmen; Berrocoso, Esther; Alba-Delgado, Cristina; Madrigal, Jose Luis M; Perez-Nievas, Beatriz G; Leza, Juan Carlos; Mico, Juan Antonio

2015-10-01

Patients with chronic pain often suffer from affective disorders and cognitive decline, which significantly impairs their quality of life. In addition, many of these patients also experience stress unrelated to their illness, which can aggravate their symptoms. These nociceptive inputs are received by the hippocampus, in which maladaptive neuroplastic changes may occur in the conditions of chronic pain. The hippocampus is a structure involved in emotionality, learning, and memory, and the proliferating cells in the granular layer of the hippocampal dentate gyrus respond to chronic pain by slowing their turnover. However, whether the maturation, survival, and integration of newborn cells in the hippocampus are affected by chronic pain remains unclear. In addition, it is unknown whether an added stress may increase this effect. We have evaluated the proliferation, differentiation, and survival of newborn hippocampal cells in a rat model of neuropathic pain (chronic constriction injury), with or without stress (chronic immobilization), by assessing the incorporation of bromodeoxyuridine into proliferating cells and immunostaining. The data obtained indicated that there was a decrease in the number of proliferating cells 8 days after nerve injury in animals subjected to neuropathic pain, an effect that was exacerbated by stress. Moreover, 4 weeks after nerve injury, neuropathic pain was associated with a loss of neuroblasts and the reduced survival of new mature neurons in the hippocampal granular layer, phenomena that also were increased by stress. By contrast, the rate of differentiation was not affected in this paradigm. Neuropathic pain negatively influences hippocampal neurogenesis (proliferation and survival), and this effect is exacerbated by stress. These neuroplastic changes may account for the affective and cognitive impairment seen in patients with chronic pain.

Can short-term oral fine motor training affect precision of task performance and induce cortical plasticity of the jaw muscles?

PubMed

Zhang, Hong; Kumar, Abhishek; Kothari, Mohit; Luo, Xiaoping; Trulsson, Mats; Svensson, Krister G; Svensson, Peter

2016-07-01

The aim was to test the hypothesis that short-term oral sensorimotor training of the jaw muscles would increase the precision of task performance and induce neuroplastic changes in the corticomotor pathways, related to the masseter muscle. Fifteen healthy volunteers performed six series with ten trials of an oral sensorimotor task. The task was to manipulate and position a spherical chocolate candy in between the anterior teeth and split it into two equal halves. The precision of the task performance was evaluated by comparing the ratio between the two split halves. A series of "hold-and-split" tasks was also performed before and after the training. The hold force and split force along with the electromyographic (EMG) activity of jaw muscles were recorded. Motor-evoked potentials and cortical motor maps of the right masseter muscle were evoked by transcranial magnetic stimulation. There was a significant effect of series on the precision of the task performance during the short-term oral sensorimotor training (P < 0.002). The hold force during the "hold-and-split" task was significantly lower after training than before the short-term training (P = 0.011). However, there was no change in the split force and the EMG activity of the jaw muscles before and after the training. Further, there was a significant increase in the amplitude of the motor-evoked potentials (P < 0.016) and in the motor cortex map areas (P = 0.033), after the short-term oral sensorimotor training. Therefore, short-term oral sensorimotor task training increased the precision of task performance and induced signs of neuroplastic changes in the corticomotor pathways, related to the masseter muscle.

Brain-derived neurotrophic factor (BDNF) serum basal levels is not affected by power training in mobility-limited older adults - A randomized controlled trial.

PubMed

Hvid, L G; Nielsen, M K F; Simonsen, C; Andersen, M; Caserotti, P

2017-07-01

Brain-derived neurotrophic factor (BDNF) is a potential important factor involved in neuroplasticity, and may be a mediator for eliciting adaptations in neuromuscular function and physical function in older individuals following physical training. As power training taxes the neural system to a very high extent, it may be particularly effective in terms of eliciting increases in systemic BDNF levels. We examined the effects of 12weeks of power training on mature BDNF (mBDNF) and total BDNF (tBDNF) in mobility-limited older adults from the Healthy Ageing Network of Competence (HANC) study. We included 47 older men and women: n=22 in the training group (TG: progressive high intensity power training, 2 sessions per week; age 82.7±5.4years, 55% women) and n=25 in the control group (CG: no interventions; age 82.2±4.5years, 76% women). Following overnight fasting, basal serum levels of mBDNF and tBDNF were assessed (human ELISA kits) at baseline and post-intervention. At baseline, mBDNF and tBDNF levels were comparable in the two groups, TG and CG. Post-intervention, no significant within-group or between-group changes were observed in mBDNF or tBDNF. Moreover, when divided into responder tertiles based upon changes in mBDNF and tBDNF (i.e. decliners, maintainers, improvers), respectively, comparable findings were observed for TG and CG. Altogether, basal systemic levels of serum mBDNF and tBDNF are not affected in mobility-limited older adults following 12-weeks of power training, and do not appear to be a major mechanistic factor mediating neuroplasticity in mobility-limited older adults. Copyright © 2017 Elsevier Inc. All rights reserved.

Reduced hippocampal N-acetyl-aspartate (NAA) as a biomarker for overweight.

PubMed

Coplan, Jeremy D; Fathy, Hassan M; Abdallah, Chadi G; Ragab, Sherif A; Kral, John G; Mao, Xiangling; Shungu, Dikoma C; Mathew, Sanjay J

2014-01-01

We previously demonstrated an inverse relationship between both dentate gyrus neurogenesis - a form of neuroplasticity - and expression of the antiapoptotic gene marker, BCL-2 and adult macaque body weight. We therefore explored whether a similar inverse correlation existed in humans between body mass index (BMI) and hippocampal N-acetyl-aspartate (NAA), a marker of neuronal integrity and putatively, neuroplasticity. We also studied the relationship of a potentially neurotoxic process, worry, to hippocampal NAA in patients with generalized anxiety disorder (GAD) and control subjects (CS). We combined two previously studied cohorts of GAD and control subjects. Using proton magnetic resonance spectroscopy imaging ((1)H MRSI) in medication-free patients with GAD (n = 29) and a matched healthy control group (n = 22), we determined hippocampal concentrations of (1) NAA (2) choline containing compounds (CHO), and (3) Creatine + phosphocreatine (CR). Data were combined from 1.5 T and 3 T scans by converting values from each cohort to z-scores. Overweight and GAD diagnosis were used as categorical variables while the Penn State Worry Questionnaire (PSWQ) and Anxiety Sensitivity Index (ASI) were used as dependent variables. Overweight subjects (BMI ≥ 25) exhibited lower NAA levels in the hippocampus than normal-weight subjects (BMI < 25) (partial Eta-squared = 0.14) controlling for age, sex and psychiatric diagnosis, and the effect was significant for the right hippocampus in both GAD patients and control subjects. An inverse linear correlation was noted in all subjects between right hippocampal NAA and BMI. High scores on the PSWQ predicted low hippocampal NAA and CR. Both BMI and worry were independent inverse predictors of hippocampal NAA. Overweight was associated with reduced NAA concentrations in the hippocampus with a strong effect size. Future mechanistic studies are warranted.

Onset age of L2 acquisition influences language network in early and late Cantonese-Mandarin bilinguals.

PubMed

Liu, Xiaojin; Tu, Liu; Wang, Junjing; Jiang, Bo; Gao, Wei; Pan, Ximin; Li, Meng; Zhong, Miao; Zhu, Zhenzhen; Niu, Meiqi; Li, Yanyan; Zhao, Ling; Chen, Xiaoxi; Liu, Chang; Lu, Zhi; Huang, Ruiwang

2017-11-01

Early second language (L2) experience influences the neural organization of L2 in neuro-plastic terms. Previous studies tried to reveal these plastic effects of age of second language acquisition (AoA-L2) and proficiency-level in L2 (PL-L2) on the neural basis of language processing in bilinguals. Although different activation patterns have been observed during language processing in early and late bilinguals by task-fMRI, few studies reported the effect of AoA-L2 and high PL-L2 on language network at resting state. In this study, we acquired resting-state fMRI (R-fMRI) data from 10 Cantonese (L1)-Mandarin (L2) early bilinguals (acquired L2: 3years old) and 11 late bilinguals (acquired L2: 6years old), and analyzed their topological properties of language networks after controlling the language daily exposure and usage as well as PL in L1 and L2. We found that early bilinguals had significantly a higher clustering coefficient, global and local efficiency, but significantly lower characteristic path length compared to late bilinguals. Modular analysis indicated that compared to late bilinguals, early bilinguals showed significantly stronger intra-modular functional connectivity in the semantic and phonetic modules, stronger inter-modular functional connectivity between the semantic and phonetic modules as well as between the phonetic and syntactic modules. Differences in global and local parameters may reflect different patterns of neuro-plasticity respectively for early and late bilinguals. These results suggested that different L2 experience influences topological properties of language network, even if late bilinguals achieve high PL-L2. Our findings may provide a new perspective of neural mechanisms related to early and late bilinguals. Copyright © 2017 Elsevier Inc. All rights reserved.

Subchronic treatment with fluoxetine and ketanserin increases hippocampal brain-derived neurotrophic factor, β-catenin and antidepressant-like effects.

PubMed

Pilar-Cuéllar, F; Vidal, R; Pazos, A

2012-02-01

5-HT(2A) receptor antagonists improve antidepressant responses when added to 5-HT-selective reuptake inhibitors (SSRIs) or tricyclic antidepressants. Here, we have studied the involvement of neuroplasticity pathways and/or the 5-hydroxytryptaminergic system in the antidepressant-like effect of this combined treatment, given subchronically. Expression of brain-derived neurotrophic factor (BDNF) and its receptor (TrkB), 5-bromo-2'-deoxyuridine (BrdU) incorporation, and β-catenin protein expression in different cellular fractions, as well as 5-HT(1A) receptor function were measured in the hippocampus of rats treated with fluoxetine, ketanserin and fluoxetine + ketanserin for 7 days, followed by a forced swimming test (FST) to analyse antidepressant efficacy. mRNA for BDNF was increased in the CA3 field and dentate gyrus of the hippocampus by combined treatment with fluoxetine + ketanserin. Expression of β-catenin was increased in total hippocampal homogenate and in the membrane fraction, but unchanged in the nuclear fraction after combined treatment with fluoxetine + ketanserin. These effects were paralleled by a decreased immobility time in the FST. There were no changes in BrdU incorporation, TrkB expression and 5-HT(1A) receptor function in any of the groups studied. The antidepressant-like effect induced by subchronic co-treatment with a SSRI and a 5-HT(2A) receptor antagonist may mainly be because of modifications in hippocampal neuroplasticity (BDNF and membrane-associated β-catenin), without a significant role for other mechanisms involved in chronic antidepressant response, such as hippocampal neuroproliferation or 5-HT(1A) receptor desensitization in the dorsal raphe nucleus. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Brain changes following four weeks of unimanual motor training: Evidence from behavior, neural stimulation, cortical thickness, and functional MRI.

PubMed

Sale, Martin V; Reid, Lee B; Cocchi, Luca; Pagnozzi, Alex M; Rose, Stephen E; Mattingley, Jason B

2017-09-01

Although different aspects of neuroplasticity can be quantified with behavioral probes, brain stimulation, and brain imaging assessments, no study to date has combined all these approaches into one comprehensive assessment of brain plasticity. Here, 24 healthy right-handed participants practiced a sequence of finger-thumb opposition movements for 10 min each day with their left hand. After 4 weeks, performance for the practiced sequence improved significantly (P < 0.05 FWE) relative to a matched control sequence, with both the left (mean increase: 53.0% practiced, 6.5% control) and right (21.0%; 15.8%) hands. Training also induced significant (cluster p-FWE < 0.001) reductions in functional MRI activation for execution of the trained sequence, relative to the control sequence. These changes were observed as clusters in the premotor and supplementary motor cortices (right hemisphere, 301 voxel cluster; left hemisphere 700 voxel cluster), and sensorimotor cortices and superior parietal lobules (right hemisphere 864 voxel cluster; left hemisphere, 1947 voxel cluster). Transcranial magnetic stimulation over the right ("trained") primary motor cortex yielded a 58.6% mean increase in a measure of motor evoked potential amplitude, as recorded at the left abductor pollicis brevis muscle. Cortical thickness analyses based on structural MRI suggested changes in the right precentral gyrus, right post central gyrus, right dorsolateral prefrontal cortex, and potentially the right supplementary motor area. Such findings are consistent with LTP-like neuroplastic changes in areas that were already responsible for finger sequence execution, rather than improved recruitment of previously nonutilized tissue. Hum Brain Mapp 38:4773-4787, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Sub-chronic agmatine treatment modulates hippocampal neuroplasticity and cell survival signaling pathways in mice.

PubMed

Freitas, Andiara E; Bettio, Luis E B; Neis, Vivian B; Moretti, Morgana; Ribeiro, Camille M; Lopes, Mark W; Leal, Rodrigo B; Rodrigues, Ana Lúcia S

2014-11-01

Agmatine is an endogenous neuromodulator which, based on animal and human studies, is a putative novel antidepressant drug. In this study, we investigated the ability of sub-chronic (21 days) p.o. agmatine administration to produce an antidepressant-like effect in the tail suspension test and examined the hippocampal cell signaling pathways implicated in such an effect. Agmatine at doses of 0.01 and 0.1 mg/kg (p.o.) produced a significant antidepressant-like effect in the tail suspension test and no effect in the open-field test. Additionally, agmatine (0.001-0.1 mg/kg, p.o.) increased the phosphorylation of protein kinase A substrates (237-258% of control), protein kinase B/Akt (Ser(473)) (116-127% of control), glycogen synthase kinase-3β (Ser(9)) (110-113% of control), extracellular signal-regulated kinases 1/2 (119-137% and 121-138% of control, respectively) and cAMP response elements (Ser(133)) (127-152% of control), and brain-derived-neurotrophic factor (137-175% of control) immunocontent in a dose-dependent manner in the hippocampus. Agmatine (0.001-0.1 mg/kg, p.o.) also reduced the c-jun N-terminal kinase 1/2 phosphorylation (77-71% and 65-51% of control, respectively). Neither protein kinase C nor p38(MAPK) phosphorylation was altered under any experimental conditions. Taken together, the present study extends the available data on the mechanisms that underlie the antidepressant action of agmatine by showing an antidepressant-like effect following sub-chronic administration. In addition, our results are the first to demonstrate the ability of agmatine to elicit the activation of cellular signaling pathways associated with neuroplasticity/cell survival and the inhibition of signaling pathways associated with cell death in the hippocampus. Copyright © 2014 Elsevier Ltd. All rights reserved.

A phenomenology of meditation-induced light experiences: traditional buddhist and neurobiological perspectives

PubMed Central

Lindahl, Jared R.; Kaplan, Christopher T.; Winget, Evan M.; Britton, Willoughby B.

2014-01-01

The scientific study of Buddhist meditation has proceeded without much attention to Buddhist literature that details the range of psychological and physiological changes thought to occur during meditation. This paper presents reports of various meditation-induced light experiences derived from American Buddhist practitioners. The reports of light experiences are classified into two main types: discrete lightforms and patterned or diffuse lights. Similar phenomena are well documented in traditional Buddhist texts but are virtually undocumented in scientific literature on meditation. Within Buddhist traditions, these phenomena are attributed a range of interpretations. However, because it is insufficient and problematic to rely solely upon the textual sources as a means of investigating the cause or significance of these phenomena, these qualitative reports are also considered in relation to scientific research on light-related experiences in the context of sensory deprivation, perceptual isolation, and clinical disorders of the visual system. The typologies derived from these studies also rely upon reports of experiences and closely match typologies derived from the qualitative study of contemporary practitioners and typologies found in Buddhist literary traditions. Taken together, these studies also provide evidence in support of the hypothesis that certain meditative practices – especially those that deliberately decrease social, kinesthetic, and sensory stimulation and emphasize focused attention – have perceptual and cognitive outcomes similar to sensory deprivation. Given that sensory deprivation increases neuroplasticity, meditation may also have an enhanced neuroplastic potential beyond ordinary experience-dependent changes. By providing and contextualizing these reports of meditation-induced light experiences, scientists, clinicians, and meditators gain a more informed view of the range of experiences that can be elicited by contemplative practices. PMID:24427148

Opposite optimal current flow directions for induction of neuroplasticity and excitation threshold in the human motor cortex.

PubMed

Sommer, Martin; Norden, Christoph; Schmack, Lars; Rothkegel, Holger; Lang, Nicolas; Paulus, Walter

2013-05-01

Directional sensitivity is relevant for the excitability threshold of the human primary motor cortex, but its importance for externally induced plasticity is unknown. To study the influence of current direction on two paradigms inducing neuroplasticity by repetitive transcranial magnetic stimulation (rTMS). We studied short-lasting after-effects induced in the human primary motor cortex of 8 healthy subjects, using 5 Hz rTMS applied in six blocks of 200 pulses each, at 90% active motor threshold. We controlled for intensity, frequency, waveform and spinal effects. Only biphasic pulses with the effective component delivered in an anterioposterior direction (henceforth posteriorly directed) in the brain yielded an increase of motor-evoked potential (MEP) amplitudes outlasting rTMS. MEP latencies and F-wave amplitudes remained unchanged. Biphasic pulses directed posteroanterior (i.e. anteriorly) were ineffective, as were monophasic pulses from either direction. A 1 Hz study in a group of 12 healthy subjects confirmed facilitation after posteriorly directed biphasic pulses only. The anisotropy of the human primary motor cortex is relevant for induction of plasticity by subtreshold rTMS, with a current flow opposite to that providing lowest excitability thresholds. This is consistent with the idea of TMS primarily targeting cortical columns of the phylogenetically new M1 in the anterior bank of the central sulcus. For these, anteriorly directed currents are soma-depolarizing, therefore optimal for low thresholds, whereas posteriorly directed currents are soma-hyperpolarizing, likely dendrite-depolarizing and bested suited for induction of plasticity. Our findings should help focus and enhance rTMS effects in experimental and clinical settings. Copyright © 2013 Elsevier Inc. All rights reserved.

Short Meditation Trainings Enhance Non-REM Sleep Low-Frequency Oscillations.

PubMed

Dentico, Daniela; Ferrarelli, Fabio; Riedner, Brady A; Smith, Richard; Zennig, Corinna; Lutz, Antoine; Tononi, Giulio; Davidson, Richard J

2016-01-01

We have recently shown higher parietal-occipital EEG gamma activity during sleep in long-term meditators compared to meditation-naive individuals. This gamma increase was specific for NREM sleep, was present throughout the entire night and correlated with meditation expertise, thus suggesting underlying long-lasting neuroplastic changes induced through prolonged training. The aim of this study was to explore the neuroplastic changes acutely induced by 2 intensive days of different meditation practices in the same group of practitioners. We also repeated baseline recordings in a meditation-naive cohort to account for time effects on sleep EEG activity. High-density EEG recordings of human brain activity were acquired over the course of whole sleep nights following intervention. Sound-attenuated sleep research room. Twenty-four long-term meditators and twenty-four meditation-naïve controls. Two 8-h sessions of either a mindfulness-based meditation or a form of meditation designed to cultivate compassion and loving kindness, hereafter referred to as compassion meditation. We found an increase in EEG low-frequency oscillatory activities (1-12 Hz, centered around 7-8 Hz) over prefrontal and left parietal electrodes across whole night NREM cycles. This power increase peaked early in the night and extended during the third cycle to high-frequencies up to the gamma range (25-40 Hz). There was no difference in sleep EEG activity between meditation styles in long-term meditators nor in the meditation naïve group across different time points. Furthermore, the prefrontal-parietal changes were dependent on meditation life experience. This low-frequency prefrontal-parietal activation likely reflects acute, meditation-related plastic changes occurring during wakefulness, and may underlie a top-down regulation from frontal and anterior parietal areas to the posterior parietal and occipital regions showing chronic, long-lasting plastic changes in long-term meditators.

Adolescent Maturational Transitions in the Prefrontal Cortex and Dopamine Signaling as a Risk Factor for the Development of Obesity and High Fat/High Sugar Diet Induced Cognitive Deficits

PubMed Central

Reichelt, Amy C.

2016-01-01

Adolescence poses as both a transitional period in neurodevelopment and lifestyle practices. In particular, the developmental trajectory of the prefrontal cortex (PFC), a critical region for behavioral control and self-regulation, is enduring, not reaching functional maturity until the early 20 s in humans. Furthermore, the neurotransmitter dopamine is particularly abundant during adolescence, tuning the brain to rapidly learn about rewards and regulating aspects of neuroplasticity. Thus, adolescence is proposed to represent a period of vulnerability towards reward-driven behaviors such as the consumption of palatable high fat and high sugar diets. This is reflected in the increasing prevalence of obesity in children and adolescents as they are the greatest consumers of “junk foods”. Excessive consumption of diets laden in saturated fat and refined sugars not only leads to weight gain and the development of obesity, but experimental studies with rodents indicate they evoke cognitive deficits in learning and memory process by disrupting neuroplasticity and altering reward processing neurocircuitry. Consumption of these high fat and high sugar diets have been reported to have a particularly pronounced impact on cognition when consumed during adolescence, demonstrating a susceptibility of the adolescent brain to enduring cognitive deficits. The adolescent brain, with heightened reward sensitivity and diminished behavioral control compared to the mature adult brain, appears to be a risk for aberrant eating behaviors that may underpin the development of obesity. This review explores the neurodevelopmental changes in the PFC and mesocortical dopamine signaling that occur during adolescence, and how these potentially underpin the overconsumption of palatable food and development of obesogenic diet-induced cognitive deficits. PMID:27790098

Enteric neuroplasticity in seawater-adapted European eel (Anguilla anguilla).

PubMed

Sorteni, C; Clavenzani, P; De Giorgio, R; Portnoy, O; Sirri, R; Mordenti, O; Di Biase, A; Parmeggiani, A; Menconi, V; Chiocchetti, R

2014-02-01

European eels live most of their lives in freshwater until spawning migration to the Sargasso Sea. During seawater adaptation, eels modify their physiology, and their digestive system adapts to the new environment, drinking salt water to compensate for the continuous water loss. In that period, eels stop feeding until spawning. Thus, the eel represents a unique model to understand the adaptive changes of the enteric nervous system (ENS) to modified salinity and starvation. To this purpose, we assessed and compared the enteric neuronal density in the cranial portion of the intestine of freshwater eels (control), lagoon eels captured in brackish water before their migration to the Sargasso Sea (T0), and starved seawater eels hormonally induced to sexual maturity (T18; 18 weeks of starvation and treatment with standardized carp pituitary extract). Furthermore, we analyzed the modification of intestinal neuronal density of hormonally untreated eels during prolonged starvation (10 weeks) in seawater and freshwater. The density of myenteric (MP) and submucosal plexus (SMP) HuC/D-immunoreactive (Hu-IR) neurons was assessed in wholemount preparations and cryosections. The number of MP and SMP HuC/D-IR neurons progressively increased from the freshwater to the salty water habitat (control > T0 > T18; P < 0.05). Compared with freshwater eels, the number of MP and SMP HuC/D-IR neurons significantly increased (P < 0.05) in the intestine of starved untreated salt water eels. In conclusion, high salinity evokes enteric neuroplasticity as indicated by the increasing number of HuC/D-IR MP and SMP neurons, a mechanism likely contributing to maintaining the body homeostasis of this fish in extreme conditions. © 2013 Anatomical Society.

Different types of exercise induce differential effects on neuronal adaptations and memory performance.

PubMed

Lin, Tzu-Wei; Chen, Shean-Jen; Huang, Tung-Yi; Chang, Chia-Yuan; Chuang, Jih-Ing; Wu, Fong-Sen; Kuo, Yu-Min; Jen, Chauying J

2012-01-01

Different exercise paradigms show differential effects on various forms of memory. We hypothesize that the differential effects of exercises on memory performance are caused by different neuroplasticity changes in relevant brain regions in response to different exercise trainings. We examined the effects of treadmill running (TR) and wheel running (WR) on the Pavlovian fear conditioning task that assesses learning and memory performance associated with the amygdala (cued conditioning) and both the amygdala and hippocampus (contextual conditioning). The skeletal muscle citrate synthase activity, an indicator of aerobic capacity, was elevated in rats received 4 w of TR, but not WR. While both TR and WR elevated the contextual conditional response, only TR facilitated the cued conditional response. Using a single-neuron labeling technique, we found that while both TR and MR enlarged the dendritic field and increased the spine density in hippocampal CA3 neurons, only TR showed these effects in basolateral amygdalar neurons. Moreover, both types of exercise upregulated synaptic proteins (i.e., TrkB and SNAP-25) in the hippocampus; however only TR showed similar effects in the amygdala. Injection of K252a, a TrkB kinase inhibitor, in the dorsal hippocampus or basolateral amygdala abolished the exercise-facilitated contextual or cued fear learning and memory performance, respectively, regardless of the types of exercise. In summary, our results supported that different types of exercise affect the performance of learning and memory via BDNF-TrkB signaling and neuroplasticity in specific brain regions. The brain region-specific neuronal adaptations are possibly induced by various levels of intensity/stress elicited by different types of exercise. Copyright © 2011 Elsevier Inc. All rights reserved.

Enhanced peripheral visual processing in congenitally deaf humans is supported by multiple brain regions, including primary auditory cortex.

PubMed

Scott, Gregory D; Karns, Christina M; Dow, Mark W; Stevens, Courtney; Neville, Helen J

2014-01-01

Brain reorganization associated with altered sensory experience clarifies the critical role of neuroplasticity in development. An example is enhanced peripheral visual processing associated with congenital deafness, but the neural systems supporting this have not been fully characterized. A gap in our understanding of deafness-enhanced peripheral vision is the contribution of primary auditory cortex. Previous studies of auditory cortex that use anatomical normalization across participants were limited by inter-subject variability of Heschl's gyrus. In addition to reorganized auditory cortex (cross-modal plasticity), a second gap in our understanding is the contribution of altered modality-specific cortices (visual intramodal plasticity in this case), as well as supramodal and multisensory cortices, especially when target detection is required across contrasts. Here we address these gaps by comparing fMRI signal change for peripheral vs. perifoveal visual stimulation (11-15° vs. 2-7°) in congenitally deaf and hearing participants in a blocked experimental design with two analytical approaches: a Heschl's gyrus region of interest analysis and a whole brain analysis. Our results using individually-defined primary auditory cortex (Heschl's gyrus) indicate that fMRI signal change for more peripheral stimuli was greater than perifoveal in deaf but not in hearing participants. Whole-brain analyses revealed differences between deaf and hearing participants for peripheral vs. perifoveal visual processing in extrastriate visual cortex including primary auditory cortex, MT+/V5, superior-temporal auditory, and multisensory and/or supramodal regions, such as posterior parietal cortex (PPC), frontal eye fields, anterior cingulate, and supplementary eye fields. Overall, these data demonstrate the contribution of neuroplasticity in multiple systems including primary auditory cortex, supramodal, and multisensory regions, to altered visual processing in congenitally deaf adults.

Dose-and gender-specific effects of resistance training on circulating levels of brain derived neurotrophic factor (BDNF) in community-dwelling older adults.

PubMed

Forti, Louis Nuvagah; Van Roie, Evelien; Njemini, Rose; Coudyzer, Walter; Beyer, Ingo; Delecluse, Christophe; Bautmans, Ivan

2015-10-01

BDNF is known to induce neuroplasticity and low circulating levels have been related to neuronal loss in older persons. Physical exercise is thought to trigger BDNF-induced neuroplasticity, but conflicting observations have been reported regarding the effects of resistance training on circulating BDNF in the elderly. These conflicting observations might reflect dose-and gender-specific differences. Fifty-six apparently healthy elderly (68 ± 5 years) participants were randomized to 12 weeks of resistance training (3×/week) at either high-resistance (HIGH, 8 Males, 10 Females, 2 × 10-15 repetitions at 80% 1 RM), low-resistance (LOW, 9 Males, 10 Females, 1 × 80-100 repetitions at 20% 1 RM), or mixed low-resistance (LOW+, 9 Males, 10 Females, 1 × 60 repetitions at 20% 1 RM followed by 1 × 10-20 repetitions at 40% 1 RM). Serum was collected for BDNF assay at baseline and after 12 weeks (24 h-48 h after the last training). 12 weeks of LOW+ exercise significantly increased BDNF levels in male (from 34.9 ± 10.7 ng/mL to 42.9 ± 11.9 ng/mL, time × group interaction p=0.013), but not in female participants. No significant change was observed in HIGH or LOW, neither in male nor female subjects. Our results show that only the mixed-low-resistance training program with a very high number of repetitions at a sufficiently high external resistance was able to increase circulating BDNF in older male participants. Training to volitional fatigue might be necessary to obtain optimal results. Additional studies are needed to unravel the underlying mechanisms, as well as to confirm the observed gender difference. Copyright © 2015 Elsevier Inc. All rights reserved.

Diffuse traumatic brain injury initially attenuates and later expands activation of the rat somatosensory whisker circuit concomitant with neuroplastic responses.

PubMed

Hall, Kelley D; Lifshitz, Jonathan

2010-04-06

Traumatic brain injury can initiate an array of chronic neurological deficits, effecting executive function, language and sensorimotor integration. Mechanical forces produce the diffuse pathology that disrupts neural circuit activation across vulnerable brain regions. The present manuscript explores the hypothesis that the extent of functional activation of brain-injured circuits is a consequence of initial disruption and consequent reorganization. In the rat, enduring sensory sensitivity to whisker stimulation directs regional analysis to the whisker barrel circuit. Adult, male rats were subjected to midline fluid percussion brain or sham injury and evaluated between 1day and 42days post-injury. Whisker somatosensory regions of the cortex and thalamus maintained cellular composition as visualized by Nissl stain. Within the first week post-injury, quantitatively less cFos activation was elicited by whisker stimulation, potentially due to axotomy within and surrounding the whisker circuit as visualized by amyloid precursor protein immunohistochemistry. Over six weeks post-injury, cFos activation after whisker stimulation showed a significant linear correlation with time in the cortex (r(2)=0.545; p=0.015), non-significant correlation in the thalamus (r(2)=0.326) and U-shaped correlation in the dentate gyrus (r(2)=0.831), all eventually exceeding sham levels. Ongoing neuroplastic responses in the cortex are evidenced by accumulating growth associated protein and synaptophysin gene expression. In the thalamus, the delayed restoration of plasticity markers may explain the broad distribution of neuronal activation extending into the striatum and hippocampus with whisker stimulation. The sprouting of diffuse-injured circuits into diffuse-injured tissue likely establishes maladaptive circuits responsible for behavioral morbidity. Therapeutic interventions to promote adaptive circuit restructuring may mitigate post-traumatic morbidity. Copyright 2010 Elsevier B.V. All rights reserved.

Thinking About Better Speech: Mental Practice for Stroke-Induced Motor Speech Impairments

PubMed Central

Page, Stephen J.; Harnish, Stacy

2012-01-01

Background Mental practice (MP) is a mind-body technique in which physical movements are cognitively rehearsed. It has shown efficacy in reducing the severity of a number of neurological impairments. Aims In the present review, we highlight recent developments in MP research, and the basis for MP use after stroke-induced motor speech disorders. Main Contribution In this review, we: (a) propose a novel conceptual model regarding the development of learned nonuse in people with motor speech impairments; (b) review the rationale and efficacy of MP for reducing the severity of stroke-induced impairments; (c) review evidence demonstrating muscular and neural activations during and following MP use; (d) review evidence showing that MP increases skill acquisition, use, and function in stroke; (e) review literature regarding neuroplasticity after stroke, including MP-induced neuroplasticity and the neural substrates underlying motor and language reacquisition; and (f) based on the above, review the rationale and clinical application of MP for stroke-induced motor speech impairments. Conclusions Support for MP use includes decades of MP neurobiological and behavioral efficacy data in a number of populations. Most recently, these data have expanded to the application of MP in neurological populations. Given increasingly demanding managed care environments, efficacious strategies that can be easily administered are needed. We also encounter clinicians who aspire to use MP, but their protocols do not contain several of the elements shown to be fundamental to effective MP implementation. Given shortfalls of some conventional aphasia and motor speech rehabilitative techniques, and uncertainty regarding optimal MP implementation, this paper introduces the neurophysiologic bases for MP, the evidence for MP use in stroke rehabilitation, and discusses its applications and considerations in patients with stroke-induced motor speech impairments. PMID:22308050

PERIAQUEDUCTAL GRAY NEUROPLASTICITY FOLLOWING CHRONIC MORPHINE VARIES WITH AGE: ROLE OF OXIDATIVE STRESS

PubMed Central

Bajic, Dusica; Berde, Charles B.; Commons, Kathryn G.

2012-01-01

The development of tolerance to the antinociceptive effects of morphine has been associated with networks within ventrolateral periaqueductal gray (vlPAG) and separately, nitric oxide signaling. Furthermore, it is known that the mechanisms that underlie tolerance differ with age. In this study, we used a rat model of antinociceptive tolerance to morphine at two ages, postnatal day (PD) 7 and adult, to determine if changes in the vlPAG related to nitric oxide signaling produced by chronic morphine exposure were age-dependent. Three pharmacological groups were analyzed: control, acute morphine, and chronic morphine group. Either morphine (10 mg/kg) or equal volume of normal saline was given subcutaneously twice daily for 6 ½ days. Animals were analyzed for morphine dose-response using Hot Plate test, and for the expression of several genes associated with nitric oxide metabolism was evaluated using rtPCR. In addition, the effect of morphine exposure on immunohistochemistry for Fos, and nNOS as well as nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) reaction at the vlPAG were measured. In both age groups acute morphine activated Fos in the vlPAG, and this effect was attenuated by chronic morphine, specifically in the vlPAG at the level of the laterodorsal tegmental nucleus (LDTg). In adults, but not PD7 rats, chronic morphine administration was associated with activation of nitric oxide function. In contrast, changes in the gene expression of PD7 rats suggested superoxide and peroxide metabolisms may be engaged. These data indicate that there is supraspinal neuroplasticity following morphine administration as early as PD7. Furthermore, oxidative stress pathways associated with chronic morphine exposure appear age-specific. PMID:22999971

A single bout of high-intensity aerobic exercise facilitates response to paired associative stimulation and promotes sequence-specific implicit motor learning

PubMed Central

Mang, Cameron S.; Snow, Nicholas J.; Campbell, Kristin L.; Ross, Colin J. D.

2014-01-01

The objectives of the present study were to evaluate the impact of a single bout of high-intensity aerobic exercise on 1) long-term potentiation (LTP)-like neuroplasticity via response to paired associative stimulation (PAS) and 2) the temporal and spatial components of sequence-specific implicit motor learning. Additionally, relationships between exercise-induced increases in systemic brain-derived neurotrophic factor (BDNF) and response to PAS and motor learning were evaluated. Sixteen young healthy participants completed six experimental sessions, including the following: 1) rest followed by PAS; 2) aerobic exercise followed by PAS; 3) rest followed by practice of a continuous tracking (CT) task and 4) a no-exercise 24-h retention test; and 5) aerobic exercise followed by CT task practice and 6) a no-exercise 24-h retention test. The CT task included an embedded repeated sequence allowing for evaluation of sequence-specific implicit learning. Slope of motor-evoked potential recruitment curves generated with transcranial magnetic stimulation showed larger increases when PAS was preceded by aerobic exercise (59.8% increase) compared with rest (14.2% increase, P = 0.02). Time lag of CT task performance on the repeated sequence improved under the aerobic exercise condition from early (−100.8 ms) to late practice (−75.2 ms, P < 0.001) and was maintained at retention (−79.2 ms, P = 0.004) but did not change under the rest condition (P > 0.16). Systemic BDNF increased on average by 3.4-fold following aerobic exercise (P = 0.003), but the changes did not relate to neurophysiological or behavioral measures (P > 0.42). These results indicate that a single bout of high-intensity aerobic exercise can prime LTP-like neuroplasticity and promote sequence-specific implicit motor learning. PMID:25257866

Enteric neuroplasticity in seawater-adapted European eel (Anguilla anguilla)

PubMed Central

Sorteni, C; Clavenzani, P; De Giorgio, R; Portnoy, O; Sirri, R; Mordenti, O; Di Biase, A; Parmeggiani, A; Menconi, V; Chiocchetti, R

2014-01-01

European eels live most of their lives in freshwater until spawning migration to the Sargasso Sea. During seawater adaptation, eels modify their physiology, and their digestive system adapts to the new environment, drinking salt water to compensate for the continuous water loss. In that period, eels stop feeding until spawning. Thus, the eel represents a unique model to understand the adaptive changes of the enteric nervous system (ENS) to modified salinity and starvation. To this purpose, we assessed and compared the enteric neuronal density in the cranial portion of the intestine of freshwater eels (control), lagoon eels captured in brackish water before their migration to the Sargasso Sea (T0), and starved seawater eels hormonally induced to sexual maturity (T18; 18 weeks of starvation and treatment with standardized carp pituitary extract). Furthermore, we analyzed the modification of intestinal neuronal density of hormonally untreated eels during prolonged starvation (10 weeks) in seawater and freshwater. The density of myenteric (MP) and submucosal plexus (SMP) HuC/D-immunoreactive (Hu-IR) neurons was assessed in wholemount preparations and cryosections. The number of MP and SMP HuC/D-IR neurons progressively increased from the freshwater to the salty water habitat (control > T0 > T18; P < 0.05). Compared with freshwater eels, the number of MP and SMP HuC/D-IR neurons significantly increased (P < 0.05) in the intestine of starved untreated salt water eels. In conclusion, high salinity evokes enteric neuroplasticity as indicated by the increasing number of HuC/D-IR MP and SMP neurons, a mechanism likely contributing to maintaining the body homeostasis of this fish in extreme conditions. PMID:24433383

Female Mimicry by Sneaker Males Has a Transcriptomic Signature in Both the Brain and the Gonad in a Sex-Changing Fish.

PubMed

Todd, Erica V; Liu, Hui; Lamm, Melissa S; Thomas, Jodi T; Rutherford, Kim; Thompson, Kelly C; Godwin, John R; Gemmell, Neil J

2018-01-01

Phenotypic plasticity represents an elegant adaptive response of individuals to a change in their environment. Bluehead wrasses (Thalassoma bifasciatum) exhibit astonishing sexual plasticity, including female-to-male sex change and discrete male morphs that differ strikingly in behavior, morphology, and gonadal investment. Using RNA-seq transcriptome profiling, we examined the genes and physiological pathways underlying flexible behavioral and gonadal differences among female, dominant (bourgeois) male, and female-mimic (sneaker) male blueheads. For the first time in any organism, we find that female mimicry by sneaker males has a transcriptional signature in both the brain and the gonad. Sneaker males shared striking similarity in neural gene expression with females, supporting the idea that males with alternative reproductive phenotypes have "female-like brains." Sneaker males also overexpressed neuroplasticity genes, suggesting that their opportunistic reproductive strategy requires a heightened capacity for neuroplasticity. Bourgeois males overexpressed genes associated with socio-sexual behaviors (e.g., isotocin), but also neuroprotective genes and biomarkers of oxidative stress and aging, indicating a hitherto unexplored cost to these males of attaining the reproductively privileged position at the top of the social hierarchy. Our novel comparison of testicular transcriptomes in a fish with male sexual polymorphism associates greater gonadal investment by sneaker males with overexpression of genes involved in cell proliferation and sperm quality control. We propose that morphological female-mimicry by sneaker male teleosts entails pervasive downregulation of androgenesis genes, consistent with low androgen production in males lacking well-developed secondary sexual characters. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Dilantin therapy in an experimental model of traumatic brain injury: effects of limited versus daily treatment on neurological and behavioral recovery.

PubMed

Darrah, Shaun D; Darrah, Shaun H; Chuang, Jerry; Mohler, Laura M; Chen, Xiangbai; Cummings, Erin E; Burnett, Tiffany; Reyes-Littaua, M Christina; Galang, Gary N; Wagner, Amy K

2011-01-01

The mechanisms by which Dilantin confers anticonvulsant benefits may also be neuroprotective by attenuating the acute excitatory insult in cortical and subcortical structures when the drug is given in the acute phase after traumatic brain injury (TBI). However, when Dilantin is used for prolonged periods, we hypothesized that it may impede recovery, synaptic plasticity may be impaired, and neuroprotective benefits may be lost. As such, we assessed the effect of daily chronic administration (75 mg/kg day 0 followed by 50 mg/kg daily i.p.) and acute administration (75 mg/kg day 0 followed by 50 mg/kg i.p. day 1) of Dilantin in young adult male rats on motor performance, y-maze exploration, Morris Water Maze (MWM), hippocampal (HC) cell survival, contusion size, and regional expression of neuroplasticity markers after controlled cortical impact (CCI) injury. Chronic daily Dilantin administration resulted in beam walking impairments on day 6, whereas acute Dilantin administration resulted in beam walking impairments on days 3 and 4. Chronic Dilantin administration also resulted in worse MWM performance, more HC cell loss and no increases in neuroplasticity markers compared to rats with CCI receiving chronic vehicle. Conversely, rats receiving acute Dilantin administration exhibited more novel arm exploration in the y-maze, greater HC cell sparing, and greater growth-associated protein 43 (GAP-43) expression in the HC ipsilateral to the CCI, compared to injured rats receiving vehicle. MWM was not influenced by acute Dilantin administration. These results suggest that there are beneficial effects of limited acute Dilantin therapy after TBI, and that extended daily Dilantin therapy has deleterious effects on neural recovery. These findings support clinical guidelines for limited use of Dilantin in seizure prophylaxis after TBI.

Training memory without aversion: Appetitive hole-board spatial learning increases adult hippocampal neurogenesis.

PubMed

Sampedro-Piquero, Patricia; Moreno-Fernández, Román D; Carmen Mañas-Padilla, M; Gil-Rodríguez, Sara; Gavito, Ana Luisa; Pavón, Francisco J; Pedraza, Carmen; García-Fernández, María; Ladrón de Guevara-Miranda, David; Santín, Luis J; Castilla-Ortega, Estela

2018-05-01

Learning experiences are potent modulators of adult hippocampal neurogenesis (AHN). However, the vast majority of findings on the learning-induced regulation of AHN derive from aversively-motivated tasks, mainly the water maze paradigm, in which stress is a confounding factor that affects the AHN outcome. Currently, little is known regarding the effect of appetitively-motivated training on AHN. Hence we studied how spatial learning to find food rewards in a hole-board maze modulates AHN (cell proliferation and immature neurons) and AHN-related hippocampal neuroplasticity markers (BDNF, IGF-II and CREB phosphorylation) in mice. The 'Trained' mice were tested for both spatial reference and working memory and compared to 'Pseudotrained' mice (exposed to different baited holes in each session, thus avoiding the reference memory component of the task) and 'Control' mice (exposed to the maze without rewards). In contrast to Pseudotrained and Control mice, the number of proliferating hippocampal cells were reduced in Trained mice, but they notably increased their population of immature neurons assessed by immunohistochemistry. This evidence shows that hole-board spatial reference learning diminishes cell proliferation in favor of enhancing young neurons' survival. Interestingly, the enhanced AHN in the Trained mice (specifically in the suprapyramidal blade) positively correlated with their reference memory performance, but not with their working memory. Furthermore, the Trained animals increased the hippocampal protein expression of all the neuroplasticity markers analyzed by western blot. Results show that the appetitively-motivated hole-board task is a useful paradigm to potentiate and/or investigate AHN and hippocampal plasticity minimizing aversive variables such as fear or stress. Copyright © 2018 Elsevier Inc. All rights reserved.

A tripeptide isolated from Bothrops atrox venom has neuroprotective and neurotrophic effects on a cellular model of Parkinson's disease.

PubMed

Martins, N M; Santos, N A G; Sartim, M A; Cintra, A C O; Sampaio, S V; Santos, A C

2015-06-25

Parkinson's disease (PD) is the second most common neurodegenerative disorder; however, there is no treatment able to prevent the loss of dopaminergic neurons or its consequences. Trophic factors such as NGF and BDNF has positive effects on different disorders of the brain, including neurodegeneration. Additionally, studies have suggested the use of venom peptides as a therapeutic strategy for neurological disorders. Therefore, in the present study, we investigated the neuroprotective activity of a peptide isolated from Bothrops atrox venom and its trophic ability by using a cellular model of dopaminergic neurotoxicity induced by 1-methyl-4-phenylpyridinium (MPP(+)) in PC12 cells. We showed that it decreased the activities of the apoptotic proteases caspase-9 (mitochondrial) and caspase-3 (executor) and increased cell viability and proliferation in this model. Additionally, it increased neuritogenesis in non-treated PC12 cells (neuronal model) as well as in PC12 cells treated with the dopaminergic neurotoxin. The amino acid sequence of the peptide was identified as Glutamic acid-Valine-Tryptophan (Glu-Val-Trp). These findings suggest that this tripeptide has the potential to protect against the dopaminergic neurons loss and that trophic stimulation of neuroplasticity might be involved in its mechanism of neuroprotection. Copyright © 2015. Published by Elsevier Ireland Ltd.

Changes in Cortical Plasticity in Relation to a History of Concussion during Adolescence

PubMed Central

Meehan, Sean K.; Mirdamadi, Jasmine L.; Martini, Douglas N.; Broglio, Steven P.

2017-01-01

Adolescence and early adulthood is a critical period for neurophysiological development potentially characterized by an increased susceptibility to the long-term effects of traumatic brain injury. The current study investigated differences in motor cortical physiology and neuroplastic potential across a cohort of young adults with adolescent concussion history and those without. Transcranial magnetic stimulation (TMS) was used to assess motor evoked potential (MEP) amplitude, short-interval cortical inhibition (SICI) and intracortical facilitation (ICF) before and after intermittent theta burst stimulation (iTBS). Pre-iTBS, MEP amplitude, but not SICI or ICF, was greater in the concussion history group. Post-iTBS, the expected increase in MEP amplitude and ICF was tempered in the concussion history group. Change in SICI was variable within the concussion history group. Post hoc assessment revealed that SICI was significantly lower in individuals whose concussion was not diagnosed at the time of injury compared to both those without a concussion history or whose concussion was medically diagnosed. Concussive impacts during adolescence appear to result in a persistent reduction of the ability to modulate facilitatory motor networks. Failure to report/identify concussive impacts close to injury during adolescence also appears to produce persistent change in inhibitory networks. These findings highlight the potential long-term impact of adolescent concussion upon motor cortical physiology. PMID:28144218

The Neural Correlates of Shoulder Apprehension: A Functional MRI Study

PubMed Central

Shitara, Hitoshi; Shimoyama, Daisuke; Sasaki, Tsuyoshi; Hamano, Noritaka; Ichinose, Tsuyoshi; Yamamoto, Atsushi; Kobayashi, Tsutomu; Osawa, Toshihisa; Iizuka, Haku; Hanakawa, Takashi; Tsushima, Yoshito; Takagishi, Kenji

2015-01-01

Although shoulder apprehension is an established clinical finding and is important for the prevention of shoulder dislocation, how this subjective perception is evoked remains unclear. We elucidated the functional neuroplasticity associated with apprehension in patients with recurrent anterior shoulder instability (RSI) using functional magnetic resonance imaging (fMRI). Twelve healthy volunteers and 14 patients with right-sided RSI performed a motor imagery task and a passive shoulder motion task. Brain activity was compared between healthy participants and those with RSI and was correlated with the apprehension intensity reported by participants after each task. Compared to healthy volunteers, participants with RSI exhibited decreased brain activity in the motor network, but increased activity in the hippocampus and amygdala. During the passive motion task, participants with RSI exhibited decreased activity in the left premotor and primary motor/somatosensory areas. Furthermore, brain activity was correlated with apprehension intensity in the left amygdala and left thalamus during the motor imagery task (memory-induced), while a correlation between apprehension intensity and brain activity was found in the left prefrontal cortex during the passive motion task (instability-induced). Our findings provide insight into the pathophysiology of RSI by identifying its associated neural alterations. We elucidated that shoulder apprehension was induced by two different factors, namely instability and memory. PMID:26351854

Translation of near infrared brain imaging to assess children with cerebral palsy

NASA Astrophysics Data System (ADS)

Alexandrakis, George; Khan, Bilal; Tian, Fenghua; Asanani, Nayan; Behbehani, Khosrow; Delgado, Mauricio R.; Liu, Hanli

2009-02-01

Cerebral palsy (CP) is the most common motor disorder of central origin in childhood and affects at least 2 children per 1000 live births every year. Neuroimaging techniques are needed to study neuroplastic rearrangements in the human brain in vivo as a result of CP. Unfortunately, accurate imaging from currently available techniques often requires the patients' complete body confinement, steadiness and minimal noise for a long period of time, which limits the success rate to less than 50% for normal children and worse for CP-affected ones. In this work we show that functional near infrared (fNIR) imaging is robust to motion artifacts and has excellent potential as a sensitive diagnostic tool for this motor disorder. We have analyzed data from pediatric normal and CP patients performing finger-tapping and handwaving motor cortex activation tasks. From these analyses we have identified both spatial and temporal metrics of NIR-based motor cortex activation patterns that can clearly distinguish between normal and CP patients. We also present data from additional patients where signal processing methods are applied to filter out concurrently recorded hemodynamic signals due to breathing and cardiac pulsation. It is shown that filtering can substantially improve the quality of activation data, thus enabling more accurate comparison of activation patterns between normal and CP-affected children.

Musicianship enhances ipsilateral and contralateral efferent gain control to the cochlea.

PubMed

Bidelman, Gavin M; Schneider, Amy D; Heitzmann, Victoria R; Bhagat, Shaum P

2017-02-01

Human hearing sensitivity is easily compromised with overexposure to excessively loud sounds, leading to permanent hearing damage. Consequently, finding activities and/or experiential factors that distinguish "tender" from "tough" ears (i.e., acoustic vulnerability) would be important for identifying people at higher risk for hearing damage. To regulate sound transmission and protect the inner ear against acoustic trauma, the auditory system modulates gain control to the cochlea via biological feedback of the medial olivocochlear (MOC) efferents, a neuronal pathway linking the lower brainstem and cochlear outer hair cells. We hypothesized that a salient form of auditory experience shown to have pervasive neuroplastic benefits, namely musical training, might act to fortify hearing through tonic engagement of these reflexive pathways. By measuring MOC efferent feedback via otoacoustic emissions (cochlear emitted sounds), we show that dynamic ipsilateral and contralateral cochlear gain control is enhanced in musically-trained individuals. Across all participants, MOC strength was correlated with the years of listeners' training suggested that efferent gain control is experience dependent. Our data provide new evidence that intensive listening experience(s) (e.g., musicianship) can strengthen the ipsi/contralateral MOC efferent system and sound regulation to the inner ear. Implications for reducing acoustic vulnerability to damaging sounds are discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

Congenital blindness is associated with large-scale reorganization of anatomical networks.

PubMed

Hasson, Uri; Andric, Michael; Atilgan, Hicret; Collignon, Olivier

2016-03-01

Blindness is a unique model for understanding the role of experience in the development of the brain's functional and anatomical architecture. Documenting changes in the structure of anatomical networks for this population would substantiate the notion that the brain's core network-level organization may undergo neuroplasticity as a result of life-long experience. To examine this issue, we compared whole-brain networks of regional cortical-thickness covariance in early blind and matched sighted individuals. This covariance is thought to reflect signatures of integration between systems involved in similar perceptual/cognitive functions. Using graph-theoretic metrics, we identified a unique mode of anatomical reorganization in the blind that differed from that found for sighted. This was seen in that network partition structures derived from subgroups of blind were more similar to each other than they were to partitions derived from sighted. Notably, after deriving network partitions, we found that language and visual regions tended to reside within separate modules in sighted but showed a pattern of merging into shared modules in the blind. Our study demonstrates that early visual deprivation triggers a systematic large-scale reorganization of whole-brain cortical-thickness networks, suggesting changes in how occipital regions interface with other functional networks in the congenitally blind. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Neuroplasticity of selective attention: Research foundations and preliminary evidence for a gene by intervention interaction

PubMed Central

Stevens, Courtney; Pakulak, Eric; Hampton Wray, Amanda; Bell, Theodore A.; Neville, Helen J.

2017-01-01

This article reviews the trajectory of our research program on selective attention, which has moved from basic research on the neural processes underlying selective attention to translational studies using selective attention as a neurobiological target for evidence-based interventions. We use this background to present a promising preliminary investigation of how genetic and experiential factors interact during development (i.e., gene × intervention interactions). Our findings provide evidence on how exposure to a family-based training can modify the associations between genotype (5-HTTLPR) and the neural mechanisms of selective attention in preschool children from lower socioeconomic status backgrounds. PMID:28819066

Neuroplasticity of selective attention: Research foundations and preliminary evidence for a gene by intervention interaction.

PubMed

Isbell, Elif; Stevens, Courtney; Pakulak, Eric; Hampton Wray, Amanda; Bell, Theodore A; Neville, Helen J

2017-08-29

This article reviews the trajectory of our research program on selective attention, which has moved from basic research on the neural processes underlying selective attention to translational studies using selective attention as a neurobiological target for evidence-based interventions. We use this background to present a promising preliminary investigation of how genetic and experiential factors interact during development (i.e., gene × intervention interactions). Our findings provide evidence on how exposure to a family-based training can modify the associations between genotype (5-HTTLPR) and the neural mechanisms of selective attention in preschool children from lower socioeconomic status backgrounds.

The exploration of meditation in the neuroscience of attention and consciousness.

PubMed

Raffone, Antonino; Srinivasan, Narayanan

2010-02-01

Many recent behavioral and neuroscientific studies have revealed the importance of investigating meditation states and traits to achieve an increased understanding of cognitive and affective neuroplasticity, attention and self-awareness, as well as for their increasingly recognized clinical relevance. The investigation of states and traits related to meditation has especially pronounced implications for the neuroscience of attention, consciousness, self-awareness, empathy and theory of mind. In this article we present the main features of meditation-based mental training and characterize the current scientific approach to meditation states and traits with special reference to attention and consciousness, in light of the articles contributed to this issue.

Pharmacological treatment of sleep disorders and its relationship with neuroplasticity.

PubMed

Abad, Vivien C; Guilleminault, Christian

2015-01-01

Sleep and wakefulness are regulated by complex brain circuits located in the brain stem, thalamus, subthalamus, hypothalamus, basal forebrain, and cerebral cortex. Wakefulness and NREM and REM sleep are modulated by the interactions between neurotransmitters that promote arousal and neurotransmitters that promote sleep. Various lines of evidence suggest that sleep disorders may negatively affect neuronal plasticity and cognitive function. Pharmacological treatments may alleviate these effects but may also have adverse side effects by themselves. This chapter discusses the relationship between sleep disorders, pharmacological treatments, and brain plasticity, including the treatment of insomnia, hypersomnias such as narcolepsy, restless legs syndrome (RLS), obstructive sleep apnea (OSA), and parasomnias.

The Effects of Long Duration Head Down Tilt Bed Rest on Neurocognitive Performance: The Effects of Exercise Interventions

NASA Technical Reports Server (NTRS)

Seidler, R. D.; Mulavara, A. P.; Koppelmans, V.; Erdeniz. B.; Kofman, I. S.; DeDios, Y. E.; Szecsy, D. L.; Riascos-Castaneda, R. F.; Wood, S. J.; Bloomberg, J. J.

2014-01-01

We are conducting ongoing experiments in which we are performing structural and functional magnetic resonance brain imaging to identify the relationships between changes in neurocognitive function and neural structural alterations following a six month International Space Station mission and following 70 days exposure to a spaceflight analog, head down tilt bedrest. Our central hypothesis is that measures of brain structure, function, and network integrity will change from pre to post intervention (spaceflight, bedrest). Moreover, we predict that these changes will correlate with indices of cognitive, sensory, and motor function in a neuroanatomically selective fashion. Our interdisciplinary approach utilizes cutting edge neuroimaging techniques and a broad ranging battery of sensory, motor, and cognitive assessments that will be conducted pre flight, during flight, and post flight to investigate potential neuroplastic and maladaptive brain changes in crewmembers following long-duration spaceflight. Success in this endeavor would 1) result in identification of the underlying neural mechanisms and operational risks of spaceflight-induced changes in behavior, and 2) identify whether a return to normative behavioral function following re-adaptation to Earth's gravitational environment is associated with a restitution of brain structure and function or instead is supported by substitution with compensatory brain processes. Our ongoing bed rest participants are also engaging in exercise studies directed by Dr. Lori Ploutz Snyder. In this presentation, I will briefly highlight the existing literature linking exercise and fitness to brain and behavioral functions. I will also overview the metrics from my study that could be investigated in relation to the exercise and control subgroups.

An adaptive semantic matching paradigm for reliable and valid language mapping in individuals with aphasia.

PubMed

Wilson, Stephen M; Yen, Melodie; Eriksson, Dana K

2018-04-17

Research on neuroplasticity in recovery from aphasia depends on the ability to identify language areas of the brain in individuals with aphasia. However, tasks commonly used to engage language processing in people with aphasia, such as narrative comprehension and picture naming, are limited in terms of reliability (test-retest reproducibility) and validity (identification of language regions, and not other regions). On the other hand, paradigms such as semantic decision that are effective in identifying language regions in people without aphasia can be prohibitively challenging for people with aphasia. This paper describes a new semantic matching paradigm that uses an adaptive staircase procedure to present individuals with stimuli that are challenging yet within their competence, so that language processing can be fully engaged in people with and without language impairments. The feasibility, reliability and validity of the adaptive semantic matching paradigm were investigated in sixteen individuals with chronic post-stroke aphasia and fourteen neurologically normal participants, in comparison to narrative comprehension and picture naming paradigms. All participants succeeded in learning and performing the semantic paradigm. Test-retest reproducibility of the semantic paradigm in people with aphasia was good (Dice coefficient = 0.66), and was superior to the other two paradigms. The semantic paradigm revealed known features of typical language organization (lateralization; frontal and temporal regions) more consistently in neurologically normal individuals than the other two paradigms, constituting evidence for validity. In sum, the adaptive semantic matching paradigm is a feasible, reliable and valid method for mapping language regions in people with aphasia. © 2018 Wiley Periodicals, Inc.

5-HT2C Receptor Knockdown in the Amygdala Inhibits Neuropathic-Pain-Related Plasticity and Behaviors.

PubMed

Ji, Guangchen; Zhang, Wei; Mahimainathan, Lenin; Narasimhan, Madhusudhanan; Kiritoshi, Takaki; Fan, Xiuzhen; Wang, Jigong; Green, Thomas A; Neugebauer, Volker

2017-02-08

Neuroplasticity in the amygdala drives pain-related behaviors. The central nucleus (CeA) serves major amygdala output functions and can generate emotional-affective behaviors and modulate nocifensive responses. The CeA receives excitatory and inhibitory inputs from the basolateral nucleus (BLA) and serotonin receptor subtype 5-HT 2C R in the BLA, but not CeA, has been implicated anxiogenic behaviors and anxiety disorders. Here, we tested the hypothesis that 5-HT 2C R in the BLA plays a critical role in CeA plasticity and neuropathic pain behaviors in the rat spinal nerve ligation (SNL) model. Local 5-HT 2C R knockdown in the BLA with stereotaxic injection of 5-HT 2C R shRNA AAV vector decreased vocalizations and anxiety- and depression-like behaviors and increased sensory thresholds of SNL rats, but had no effect in sham controls. Extracellular single-unit recordings of CeA neurons in anesthetized rats showed that 5-HT 2C R knockdown blocked the increase in neuronal activity (increased responsiveness, irregular spike firing, and increased burst activity) in SNL rats. At the synaptic level, 5-HT 2C R knockdown blocked the increase in excitatory transmission from BLA to CeA recorded in brain slices from SNL rats using whole-cell patch-clamp conditions. Inhibitory transmission was decreased by 5-HT 2C R knockdown in control and SNL conditions to a similar degree. The findings can be explained by immunohistochemical data showing increased expression of 5-HT 2C R in non-GABAergic BLA cells in SNL rats. The results suggest that increased 5-HT 2C R in the BLA contributes to neuropathic-pain-related amygdala plasticity by driving synaptic excitation of CeA neurons. As a rescue strategy, 5-HT 2C R knockdown in the BLA inhibits neuropathic-pain-related behaviors. SIGNIFICANCE STATEMENT Neuroplasticity in the amygdala has emerged as an important pain mechanism. This study identifies a novel target and rescue strategy to control abnormally enhanced amygdala activity in an animal model of neuropathic pain. Specifically, an integrative approach of gene transfer, systems and brain slice electrophysiology, behavior, and immunohistochemistry was used to advance the novel concept that serotonin receptor subtype 5-HT 2C contributes critically to the imbalance between excitatory and inhibitory drive of amygdala output neurons. Local viral vector-mediated 5-HT 2C R knockdown in the amygdala normalizes the imbalance, decreases neuronal activity, and inhibits neuropathic-pain-related behaviors. The study provides valuable insight into serotonin receptor (dys)function in a limbic brain area. Copyright © 2017 the authors 0270-6474/17/371378-16$15.00/0.

Ventral Tegmental Area Dopamine Cell Activation during Male Rat Sexual Behavior Regulates Neuroplasticity and d-Amphetamine Cross-Sensitization following Sex Abstinence.

PubMed

Beloate, Lauren N; Omrani, Azar; Adan, Roger A; Webb, Ian C; Coolen, Lique M

2016-09-21

Experience with sexual behavior causes cross-sensitization of amphetamine reward, an effect dependent on a period of sexual reward abstinence. We previously showed that ΔFosB in the nucleus accumbens (NAc) is a key mediator of this cross-sensitization, potentially via dopamine receptor activation. However, the role of mesolimbic dopamine for sexual behavior or cross-sensitization between natural and drug reward is unknown. This was tested using inhibitory designer receptors exclusively activated by designer drugs in ventral tegmental area (VTA) dopamine cells. rAAV5/hSvn-DIO-hm4D-mCherry was injected into the VTA of TH::Cre adult male rats. Males received clozapine N-oxide (CNO) or vehicle injections before each of 5 consecutive days of mating or handling. Following an abstinence period of 7 d, males were tested for amphetamine conditioned place preference (CPP). Next, males were injected with CNO or vehicle before mating or handling for analysis of mating-induced cFos, sex experience-induced ΔFosB, and reduction of VTA dopamine soma size. Results showed that CNO did not affect mating behavior. Instead, CNO prevented sexual experience-induced cross-sensitization of amphetamine CPP, ΔFosB in the NAc and medial prefrontal cortex, and decreases in VTA dopamine soma size. Expression of hm4D-mCherry was specific to VTA dopamine cells and CNO blocked excitation and mating-induced cFos expression in VTA dopamine cells. These findings provide direct evidence that VTA dopamine activation is not required for initiation or performance of sexual behavior. Instead, VTA dopamine directly contributes to increased vulnerability for drug use following loss of natural reward by causing neuroplasticity in the mesolimbic pathway during the natural reward experience. Drugs of abuse act on the neural pathways that mediate natural reward learning and memory. Exposure to natural reward behaviors can alter subsequent drug-related reward. Specifically, experience with sexual behavior, followed by a period of abstinence from sexual behavior, causes increased reward for amphetamine in male rats. This study demonstrates that activation of ventral tegmental area dopamine neurons during sexual experience regulates cross-sensitization of amphetamine reward. Finally, ventral tegmental area dopamine cell activation is essential for experience-induced neural adaptations in the nucleus accumbens, prefrontal cortex, and ventral tegmental area. These findings demonstrate a role of mesolimbic dopamine in the interaction between natural and drug rewards, and identify mesolimbic dopamine as a key mediator of changes in vulnerability for drug use after loss of natural reward. Copyright © 2016 the authors 0270-6474/16/369949-13$15.00/0.

Clinical features and pathophysiology of Complex Regional Pain Syndrome – current state of the art

PubMed Central

Marinus, Johan; Moseley, G. Lorimer; Birklein, Frank; Baron, Ralf; Maihöfner, Christian; Kingery, Wade S.; van Hilten, Jacobus J.

2017-01-01

That a minor injury can trigger a complex regional pain syndrome (CRPS) - multiple system dysfunction, severe and often chronic pain and disability - has fascinated scientists and perplexed clinicians for decades. However, substantial advances across several medical disciplines have recently increased our understanding of CRPS. Compelling evidence implicates biological pathways that underlie aberrant inflammation, vasomotor dysfunction, and maladaptive neuroplasticity in the clinical features of CRPS. Collectively, the evidence points to CRPS being a multifactorial disorder that is associated with an aberrant host response to tissue injury. Varying susceptibility to perturbed regulation of any of the underlying biological pathways probably accounts for the clinical heterogeneity of CRPS. PMID:21683929

Dynamic Neuroplasticity after Human Prefrontal Cortex Damage

PubMed Central

Voytek, Bradley; Davis, Matar; Yago, Elena; Barceló, Francisco; Vogel, Edward K.; Knight, Robert T.

2010-01-01

Summary Memory and attention deficits are common after prefrontal cortex (PFC) damage, yet people generally recover some function over time. Recovery is thought to be dependent upon undamaged brain regions but the temporal dynamics underlying cognitive recovery are poorly understood. Here we provide evidence that the intact PFC compensates for damage in the lesioned PFC on a trial-by-trial basis dependent on cognitive load. The extent of this rapid functional compensation is indexed by transient increases in electrophysiological measures of attention and memory in the intact PFC, detectable within a second after stimulus presentation and only when the lesioned hemisphere is challenged. These observations provide evidence supporting a dynamic and flexible model of compensatory neural plasticity. PMID:21040843

Group psychotherapy and neuro-plasticity: an attachment theory perspective.

PubMed

Flores, Philip J

2010-10-01

This article selectively highlights relevant areas of neuroscience research which have direct application for attachment theory and group psychotherapy. Emerging evidence from the neurosciences is revealing that the developing brain of the infant, sculpted by the earliest attachment relationships, continues to be malleable in adulthood and can be profoundly influenced by ongoing relationships throughout one's lifespan. Advances in the neurosciences are also supporting the idea that strong attachment bonds and external interpersonal interactions that arise within the context of these attachments are registered as a person's neurophysiology and neurobiology. Attachment theory in particular provides a common language and conceptual framework from which the contributions from the neurosciences can be made applicable to group psychotherapy.

Brain-computer interfaces for post-stroke motor rehabilitation: a meta-analysis.

PubMed

Cervera, María A; Soekadar, Surjo R; Ushiba, Junichi; Millán, José Del R; Liu, Meigen; Birbaumer, Niels; Garipelli, Gangadhar

2018-05-01

Brain-computer interfaces (BCIs) can provide sensory feedback of ongoing brain oscillations, enabling stroke survivors to modulate their sensorimotor rhythms purposefully. A number of recent clinical studies indicate that repeated use of such BCIs might trigger neurological recovery and hence improvement in motor function. Here, we provide a first meta-analysis evaluating the clinical effectiveness of BCI-based post-stroke motor rehabilitation. Trials were identified using MEDLINE, CENTRAL, PEDro and by inspection of references in several review articles. We selected randomized controlled trials that used BCIs for post-stroke motor rehabilitation and provided motor impairment scores before and after the intervention. A random-effects inverse variance method was used to calculate the summary effect size. We initially identified 524 articles and, after removing duplicates, we screened titles and abstracts of 473 articles. We found 26 articles corresponding to BCI clinical trials, of these, there were nine studies that involved a total of 235 post-stroke survivors that fulfilled the inclusion criterion (randomized controlled trials that examined motor performance as an outcome measure) for the meta-analysis. Motor improvements, mostly quantified by the upper limb Fugl-Meyer Assessment (FMA-UE), exceeded the minimal clinically important difference (MCID=5.25) in six BCI studies, while such improvement was reached only in three control groups. Overall, the BCI training was associated with a standardized mean difference of 0.79 (95% CI: 0.37 to 1.20) in FMA-UE compared to control conditions, which is in the range of medium to large summary effect size. In addition, several studies indicated BCI-induced functional and structural neuroplasticity at a subclinical level. This suggests that BCI technology could be an effective intervention for post-stroke upper limb rehabilitation. However, more studies with larger sample size are required to increase the reliability of these results.

A novel neural-inspired learning algorithm with application to clinical risk prediction.

PubMed

Tay, Darwin; Poh, Chueh Loo; Kitney, Richard I

2015-04-01

Clinical risk prediction - the estimation of the likelihood an individual is at risk of a disease - is a coveted and exigent clinical task, and a cornerstone to the recommendation of life saving management strategies. This is especially important for individuals at risk of cardiovascular disease (CVD) given the fact that it is the leading causes of death in many developed counties. To this end, we introduce a novel learning algorithm - a key factor that influences the performance of machine learning-based prediction models - and utilities it to develop CVD risk prediction tool. This novel neural-inspired algorithm, called the Artificial Neural Cell System for classification (ANCSc), is inspired by mechanisms that develop the brain and empowering it with capabilities such as information processing/storage and recall, decision making and initiating actions on external environment. Specifically, we exploit on 3 natural neural mechanisms responsible for developing and enriching the brain - namely neurogenesis, neuroplasticity via nurturing and apoptosis - when implementing ANCSc algorithm. Benchmark testing was conducted using the Honolulu Heart Program (HHP) dataset and results are juxtaposed with 2 other algorithms - i.e. Support Vector Machine (SVM) and Evolutionary Data-Conscious Artificial Immune Recognition System (EDC-AIRS). Empirical experiments indicate that ANCSc algorithm (statistically) outperforms both SVM and EDC-AIRS algorithms. Key clinical markers identified by ANCSc algorithm include risk factors related to diet/lifestyle, pulmonary function, personal/family/medical history, blood data, blood pressure, and electrocardiography. These clinical markers, in general, are also found to be clinically significant - providing a promising avenue for identifying potential cardiovascular risk factors to be evaluated in clinical trials. Copyright © 2015 Elsevier Inc. All rights reserved.

The Effects of Spaceflight and a Spaceflight Analog on Neurocognitive Perfonnance: Extent, Longevity, and Neural Bases

NASA Technical Reports Server (NTRS)

Seidler, R. D.; Mulavara, A. P.; Koppelmans, V.; Erdeniz, B.; Kofman, I. S.; DeDios, Y. E.; Szecsy, D. L.; Riascos-Castaneda, R. F.; Wood, S. J.; Bloomberg, J. J.

2014-01-01

We are conducting ongoing experiments in which we are performing structural and functional magnetic resonance brain imaging to identify the relationships between changes in neurocognitive function and neural structural alterations following a six month International Space Station mission and following 70 days exposure to a spaceflight analog, head down tilt bedrest. Our central hypothesis is that measures of brain structure, function, and network integrity will change from pre to post intervention (spaceflight, bedrest). Moreover, we predict that these changes will correlate with indices of cognitive, sensory, and motor function in a neuroanatomically selective fashion. Our interdisciplinary approach utilizes cutting edge neuroimaging techniques and a broad ranging battery of sensory, motor, and cognitive assessments that will be conducted pre flight, during flight, and post flight to investigate potential neuroplastic and maladaptive brain changes in crewmembers following long-duration spaceflight. Success in this endeavor would 1) result in identification of the underlying neural mechanisms and operational risks of spaceflight-induced changes in behavior, and 2) identify whether a return to normative behavioral function following re-adaptation to Earth's gravitational environment is associated with a restitution of brain structure and function or instead is supported by substitution with compensatory brain processes. With the bedrest study, we will be able to determine the neural and neurocognitive effects of extended duration unloading, reduced sensory inputs, and increased cephalic fluid distribution. This will enable us to parse out the multiple mechanisms contributing to any spaceflight-induced neural structural and behavioral changes that we observe in the flight study. In this presentation I will discuss preliminary results from six participants who have undergone the bed rest protocol. These individuals show decrements in balance and functional mobility, and alterations in brain structure and function, in association with extended bed rest.

Dynamic neural network reorganization associated with second language vocabulary acquisition: a multimodal imaging study.

PubMed

Hosoda, Chihiro; Tanaka, Kanji; Nariai, Tadashi; Honda, Manabu; Hanakawa, Takashi

2013-08-21

It remains unsettled whether human language relies exclusively on innately privileged brain structure in the left hemisphere or is more flexibly shaped through experiences, which induce neuroplastic changes in potentially relevant neural circuits. Here we show that learning of second language (L2) vocabulary and its cessation can induce bidirectional changes in the mirror-reverse of the traditional language areas. A cross-sectional study identified that gray matter volume in the inferior frontal gyrus pars opercularis (IFGop) and connectivity of the IFGop with the caudate nucleus and the superior temporal gyrus/supramarginal (STG/SMG), predominantly in the right hemisphere, were positively correlated with L2 vocabulary competence. We then implemented a cohort study involving 16 weeks of L2 training in university students. Brain structure before training did not predict the later gain in L2 ability. However, training intervention did increase IFGop volume and reorganization of white matter including the IFGop-caudate and IFGop-STG/SMG pathways in the right hemisphere. These "positive" plastic changes were correlated with the gain in L2 ability in the trained group but were not observed in the control group. We propose that the right hemispheric network can be reorganized into language-related areas through use-dependent plasticity in young adults, reflecting a repertoire of flexible reorganization of the neural substrates responding to linguistic experiences.

Statistical learning of multisensory regularities is enhanced in musicians: An MEG study.

PubMed

Paraskevopoulos, Evangelos; Chalas, Nikolas; Kartsidis, Panagiotis; Wollbrink, Andreas; Bamidis, Panagiotis

2018-07-15

The present study used magnetoencephalography (MEG) to identify the neural correlates of audiovisual statistical learning, while disentangling the differential contributions of uni- and multi-modal statistical mismatch responses in humans. The applied paradigm was based on a combination of a statistical learning paradigm and a multisensory oddball one, combining an audiovisual, an auditory and a visual stimulation stream, along with the corresponding deviances. Plasticity effects due to musical expertise were investigated by comparing the behavioral and MEG responses of musicians to non-musicians. The behavioral results indicated that the learning was successful for both musicians and non-musicians. The unimodal MEG responses are consistent with previous studies, revealing the contribution of Heschl's gyrus for the identification of auditory statistical mismatches and the contribution of medial temporal and visual association areas for the visual modality. The cortical network underlying audiovisual statistical learning was found to be partly common and partly distinct from the corresponding unimodal networks, comprising right temporal and left inferior frontal sources. Musicians showed enhanced activation in superior temporal and superior frontal gyrus. Connectivity and information processing flow amongst the sources comprising the cortical network of audiovisual statistical learning, as estimated by transfer entropy, was reorganized in musicians, indicating enhanced top-down processing. This neuroplastic effect showed a cross-modal stability between the auditory and audiovisual modalities. Copyright © 2018 Elsevier Inc. All rights reserved.

Structure changes of human brain gray matter neurons and astrocytes in acute local ischemic injury.

PubMed

Sergeeva, S P; Shishkina, L V; Litvitskiy, P F; Breslavich, I D; Vinogradov, E V

2016-01-01

The purpose to identify key morphological features of the Astrocytes and Neurons in the acute local cerebral ischemia human cortex. Left middle cerebral artery ischemic stroke died persons (n = 9) brain tissue samples from 3 zones: 1st - contiguous to the tissue necrotic damage site zone, 2nd - 5-10 cm distant from the previous one, 3rd - the damage site symmetrical zone of the contralateral hemisphere. For GFAP, MAP-2, NSE, p53 detection indirect immunoperoxidase immunohistochemical staining method has been used. Also, the samples were Nissl and Hematoxylin-Eosin stained. The most pronounced changes in the quantity and morphological structure of astrocytes and neurons are found in directly adjacent to the necrotic core region of theleft middle cerebral artery ischemic stroke brain. This indicates the prevalence of the inflammation processes around the area of nerve tissueischemic destruction. Morphological changes of neurons and astrocytes, apoptosis, enhanced neuron-astrocyte interaction found in the area bordering on necrotic core (5-10 cm from it), as well as ischemic hearth symmetrical sites of the contralateral hemisphere. This interaction is essential for the neuroplasticityrealization in the local ischemic brain injury. The results obtained were shown the nerve tissue morphological characteristics changes occur in local cerebral cortex ischemic injury not only in the lesion, but also in the contralateral hemisphere. These changes are probably related to the implementation of neuroplasticity.

Long-Term Alterations in Neural and Endocrine Processes Induced by Motherhood

PubMed Central

Bridges, Robert S.

2015-01-01

The reproductive experience of pregnancy, lactation and motherhood can significantly remodel the female’s biological state, affecting endocrine, neuroendocrine, neural, and immunological processes. The brain, pituitary gland, liver, thymus, and mammary tissue are among the structures that are modified by reproductive experience. The present review that focuses on rodent research, but also includes pertinent studies in sheep and other species, identifies specific changes in these processes brought about by the biological states of pregnancy, parturition, and lactation and how the components of reproductive experience contribute to the remodeling of the maternal brain and organ systems. Findings indicate that prior parity alters key circulating hormone levels and neural receptor gene expression. Moreover, reproductive experience results in modifications in neural processes and glial support. The possible role of pregnancy-induced neurogenesis is considered in the context of neuroplasticity and behavior, and the effects of reproductive experience on maternal memory, i.e. the retention of maternal behavior, together with anxiety and learning are presented. Together, these sets of findings support the concept that the neural and biological state of the adult female is significantly and dramatically altered on a long-term basis by the experiences of parity and motherhood. Remodeling of the maternal brain and other biological systems is posited to help facilitate adaptations to environmental/ecological challenges as the female raises young and ages. PMID:26388065

Gene transcripts selectively down-regulated in the shell of the nucleus accumbens long after heroin self-administration are up-regulated in the core independent of response contingency.

PubMed

Jacobs, Edwin H; de Vries, Taco J; Smit, August B; Schoffelmeer, Anton N M

2004-01-01

Long-term drug-induced alterations in neurotransmission within the nucleus accumbens (NAc) shell and core may underlie relapse to drug-seeking behavior and drug-taking upon re-exposure to drugs and drug-associated stimuli (cues) during abstinence. Using an open screening strategy, we recently identified 25 gene transcripts, encoding for proteins involved in neuronal functioning and structure that are down-regulated in rat NAc shell after contingent (active), but not after non-contingent (passive), heroin administration. Studying the expression of the same transcripts in the NAc core by means of quantitative PCR, we now demonstrate that most of these transcripts are up-regulated in that NAc subregion long (3 weeks) after heroin self-administration in rats. A similar up-regulation in gene expression was also apparent in the NAc core of animals with a history of non-contingent heroin administration (yoked controls). These data indicate that heroin self-administration differentially regulates genes in the NAc core as compared with the shell. Moreover, whereas cognitive processes involved in active drug self-administration (e.g., instrumental learning) seems to direct gene expression in the NAc shell, neuroplasticity in the NAc core may be due to the pharmacological effects of heroin (including Pavlovian conditioning), as expressed in rats upon contingent as well as non-contingent administration of heroin.

Diffusion tensor MRI tractography reveals increased fractional anisotropy (FA) in arcuate fasciculus following music-cued motor training.

PubMed

Moore, Emma; Schaefer, Rebecca S; Bastin, Mark E; Roberts, Neil; Overy, Katie

2017-08-01

Auditory cues are frequently used to support movement learning and rehabilitation, but the neural basis of this behavioural effect is not yet clear. We investigated the microstructural neuroplasticity effects of adding musical cues to a motor learning task. We hypothesised that music-cued, left-handed motor training would increase fractional anisotropy (FA) in the contralateral arcuate fasciculus, a fibre tract connecting auditory, pre-motor and motor regions. Thirty right-handed participants were assigned to a motor learning condition either with (Music Group) or without (Control Group) musical cues. Participants completed 20minutes of training three times per week over four weeks. Diffusion tensor MRI and probabilistic neighbourhood tractography identified FA, axial (AD) and radial (RD) diffusivity before and after training. Results revealed that FA increased significantly in the right arcuate fasciculus of the Music group only, as hypothesised, with trends for AD to increase and RD to decrease, a pattern of results consistent with activity-dependent increases in myelination. No significant changes were found in the left ipsilateral arcuate fasciculus of either group. This is the first evidence that adding musical cues to movement learning can induce rapid microstructural change in white matter pathways in adults, with potential implications for therapeutic clinical practice. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Multiple neurotoxic effects of haloperidol resulting in neuronal death.

PubMed

Nasrallah, Henry A; Chen, Alexander T

2017-08-01

Several published studies have reported an association between antipsychotic medications, especially first-generation agents, and a decline in gray matter volume. This prompted us to review the possible neurotoxic mechanisms of first-generation antipsychotics (FGAs), especially haloperidol, which has been widely used over the past several decades. A PubMed search was conducted using the keywords haloperidol, antipsychotic, neurotoxicity, apoptosis, oxidative stress, and neuroplasticity. No restrictions were placed on the date of the articles or language. Studies with a clearly described methodology were included. Animal, cell culture, and human tissue studies were identified. Thirty reports met the criteria for the search. All studies included haloperidol; a few also included other FGAs (fluphenazine and perphenazine) and/or second-generation agents (SGAs) (aripiprazole, paliperidone, and risperidone). A neurotoxic effect of haloperidol and other FGAs was a common theme across all studies. Minimal (mainly at high doses) or no neurotoxic effects were noted in SGAs. A review of the literature suggests that haloperidol exerts measurable neurotoxic effects at all doses via many molecular mechanisms that lead to neuronal death. A similar effect was observed in 2 other FGAs, but the effect in SGAs was much smaller and occurred mainly at high doses. A stronger binding to serotonin 5HT-2A receptors than to dopamine D2 receptors may have a neuroprotective effect among SGAs. Further studies are warranted to confirm these findings.

What does the electroencephalogram tell us about the mechanisms of action of ECT in major depressive disorders?

PubMed

Farzan, Faranak; Boutros, Nash N; Blumberger, Daniel M; Daskalakis, Zafiris J

2014-06-01

Electroconvulsive therapy (ECT) remains to be one of the most effective treatment options in treatment-resistant major depressive disorder (MDD). From the early days, researchers have embarked on extracting information from electroencephalography (EEG) recordings before, during, and after ECT to identify neurophysiological targets of ECT and discover EEG predictors of response to ECT in patients with MDD. In this article, we provide an overview of visually detected and quantitative EEG features that could help in furthering our understanding of the mechanisms of action of ECT in MDD. We further discuss the EEG findings in the context of postulated hypotheses of ECT therapeutic pathways. We introduce an alternative and unifying hypothesis suggesting that ECT may exert its therapeutic efficacy through resetting the aberrant functional connectivity and promoting the generation of new and healthy connections in brain regions implicated in MDD pathophysiology, a mechanism that may be in part mediated by the ECT-induced activation of inhibitory and neuroplasticity mechanisms. We further discuss the added value of EEG markers in the larger context of ECT research and as complementary to neuroimaging and genetic markers. We conclude by drawing attention to the need for longitudinal studies in large cohort of patients and the need for standardization and validation of EEG algorithms of functional connectivity across studies to facilitate the translation of EEG correlates of ECT response in routine clinical practice.

Cardiorespiratory fitness is differentially associated with cortical thickness in young and older adults

PubMed Central

Williams, Victoria; Hayes, Jasmeet P.; Forman, Daniel E.; Salat, David H.; Sperling, Reisa A.; Verfaellie, Mieke; Hayes, Scott M.

2016-01-01

Aging is associated with reductions in gray matter volume and cortical thickness. One factor that may play a role in mitigating age-associated brain decline is cardiorespiratory fitness (CRF). Although previous work has identified a positive association between CRF and gray matter volume, the relationship between CRF and cortical thickness, which serves as a more sensitive indicator of gray matter integrity, has yet to be assessed in healthy young and older adults. To address this gap in the literature, 32 young and 29 older adults completed treadmill-based progressive maximal exercise testing to assess CRF (peak VO2), and structural magnetic resonance imaging (MRI) to determine vertex-wise surface-based cortical thickness metrics. Results indicated a significant CRF by age group interaction such that Peak VO2 was associated with thicker cortex in older adults but with thinner cortex in young adults. Notably, the majority of regions demonstrating a positive association between peak VO2 and cortical thickness in older adults overlapped with brain regions showing significant age-related cortical thinning. Further, when older adults were categorized as high or low fit based on normative data, we observed a stepwise pattern whereby cortex was thickest in young adults, intermediate in high fit older adults and thinnest in low fit older adults. Overall, these results support the notion that CRF-related neuroplasticity may reduce although not eliminate age-related cortical atrophy. PMID:27989841

Protocol for a randomized controlled trial of piano training on cognitive and psychosocial outcomes.

PubMed

Bugos, Jennifer

2018-05-09

Age-related cognitive decline and cognitive impairment represent the fastest growing health epidemic worldwide among those over 60. There is a critical need to identify effective and novel complex cognitive interventions to promote successful aging. Since piano training engages cognitive and bimanual sensorimotor processing, we hypothesize that piano training may serve as an effective cognitive intervention, as it requires sustained attention and engages an executive network that supports generalized cognition and emotional control. Here, I describe the protocol of a randomized controlled trial (RCT) to evaluate the impact of piano training on cognitive performance in adulthood, a period associated with decreased neuroplasticity. In this cluster RCT, healthy older adults (age 60-80) were recruited and screened to control for confounding variables. Eligible participants completed an initial 3-h assessment of standardized cognitive and psychosocial measures. Participants were stratified by age, education, and estimate of intelligence and randomly assigned to one of three groups: piano training, computer brain training, or a no-treatment control group. Computer brain training consisted of progressively difficult auditory cognitive exercises (Brain HQ; Posit Science, 2010). Participants assigned to training groups completed a 16-week program that met twice a week for 90 minutes. Upon program completion and at a 3-month follow-up, training participants and no-treatment controls completed a posttest visit lasting 2.5 hours. © 2018 New York Academy of Sciences.

Role of the ventral tegmental area in methamphetamine extinction: AMPA receptor-mediated neuroplasticity

PubMed Central

Chen, Han-Ting

2015-01-01

The molecular mechanisms underlying drug extinction remain largely unknown, although a role for medial prefrontal cortex (mPFC) glutamate neurons has been suggested. Considering that the mPFC sends glutamate efferents to the ventral tegmental area (VTA), we tested whether the VTA is involved in methamphetamine (METH) extinction via conditioned place preference (CPP). Among various METH-CPP stages, we found that the amount of phospho-GluR1/Ser845 increased in the VTA at behavioral extinction, but not the acquisition or withdrawal stage. Via surface biotinylation, we found that levels of membrane GluR1 were significantly increased during METH-CPP extinction, while no change was observed at the acquisition stage. Specifically, the number of dendritic spines in the VTA was increased at behavioral extinction, but not during acquisition. To validate the role of the mPFC in METH-CPP extinction, we lesioned the mPFC. Ibotenic acid lesioning of the mPFC did not affect METH-CPP acquisition, however, it abolished the extinction stage and reversed the enhanced phospho-GluR1/Ser845 levels as well as increases in VTA dendritic spines during METH-CPP extinction. Overall, this study demonstrates that the mPFC plays a critical role in METH-CPP extinction and identifies the VTA as an alternative target in mediating the extinction of drug conditioning. PMID:25691515

Cardiorespiratory fitness is differentially associated with cortical thickness in young and older adults.

PubMed

Williams, Victoria J; Hayes, Jasmeet P; Forman, Daniel E; Salat, David H; Sperling, Reisa A; Verfaellie, Mieke; Hayes, Scott M

2017-02-01

Aging is associated with reductions in gray matter volume and cortical thickness. One factor that may play a role in mitigating age-associated brain decline is cardiorespiratory fitness (CRF). Although previous work has identified a positive association between CRF and gray matter volume, the relationship between CRF and cortical thickness, which serves as a more sensitive indicator of gray matter integrity, has yet to be assessed in healthy young and older adults. To address this gap in the literature, 32 young and 29 older adults completed treadmill-based progressive maximal exercise testing to assess CRF (peak VO 2 ), and structural magnetic resonance imaging (MRI) to determine vertex-wise surface-based cortical thickness metrics. Results indicated a significant CRF by age group interaction such that Peak VO 2 was associated with thicker cortex in older adults but with thinner cortex in young adults. Notably, the majority of regions demonstrating a positive association between peak VO 2 and cortical thickness in older adults overlapped with brain regions showing significant age-related cortical thinning. Further, when older adults were categorized as high or low fit based on normative data, we observed a stepwise pattern whereby cortex was thickest in young adults, intermediate in high fit older adults and thinnest in low fit older adults. Overall, these results support the notion that CRF-related neuroplasticity may reduce although not eliminate age-related cortical atrophy. Published by Elsevier Inc.

Robotic gait assistive technology as means to aggressive mobilization strategy in acute rehabilitation following severe diffuse axonal injury: a case study.

PubMed

Stam, Daniel; Fernandez, Jennifer

2017-07-01

Diffuse axonal injury is a prominent cause of disablement post-traumatic brain injury. Utilization of the rapid expansion of our current scientific knowledge base combined with greater access to neurological and assistive technology as adjuncts to providing sensorimotor experience may yield innovative new approaches to rehabilitation based upon a dynamic model of brain response following injury. A 24-year-old female who sustained a traumatic brain injury, bilateral subdural hemorrhage, subarachnoid hemorrhage and severe diffuse axonal injury secondary to a motor vehicle collision. Evidence-based appraisal of present literature suggests a link between graded intensity of aerobic activity to facilitation of neuro-plastic change and up-regulation of neurotrophins essential to functional recovery post-diffuse axonal injury. Following resolution of paroxysmal autonomic instability with dystonia, aggressive early mobilization techniques were progressed utilizing robotic assistive gait technology in combination with conventional therapy. This approach allowed for arguably greater repetition and cardiovascular demands across a six-month inpatient rehabilitation stay. Outcomes in this case suggest that the use of assistive technology to adjunct higher level and intensity rehabilitation strategies may be a safe and effective means towards reduction of disablement following severe traumatic brain and neurological injury. Implications for Rehabilitation Functional recovery and neuroplasticity following diffuse neurological injury involves a complex process determined by the sensorimotor experience provided by rehabilitation clinicians. This process is in part modulated by intrinsic brain biochemical processes correlated to cardiovascular intensity of the activity provided. It is important that rehabilitation professionals monitor physiological response to higher intensity activities to provide an adaptive versus maladaptive response of central nervous system plasticity with activity. Identification of early mobilization parameters and skill acquisition may assist selection of gait assistive technology adjunct in progressing early optimal physical rehabilitation outcomes in the acute inpatient setting.

Would transcranial direct current stimulation (tDCS) enhance the effects of working memory training in older adults with mild neurocognitive disorder due to Alzheimer's disease: study protocol for a randomized controlled trial.

PubMed

Cheng, Calvin P W; Chan, Sandra S M; Mak, Arthur D P; Chan, Wai Chi; Cheng, Sheung Tak; Shi, Lin; Wang, Defeng; Lam, Linda Chiu-Wa

2015-10-24

There has been longstanding interesting in cognitive training for older adults with cognitive impairment. In this study, we will investigate the effects of working memory training, and explore augmentation strategies that could possibly consolidate the effects in older adults with mild neurocognitive disorder. Transcranial direct current stimulation (tDCS) has been demonstrated to affect the neuronal excitability and reported to enhance memory performance. As tDCS may also modulate cognitive function through changes in neuroplastic response, it would be adopted as an augmentation strategy for working memory training in the present study. This is a 4-week intervention double-blind randomized controlled trial (RCT) of tDCS. Chinese older adults (aged 60 to 90 years) with mild neurocognitive disorder due to Alzheimer's disease (DSM-5 criteria) would be randomized into a 4-week intervention of either tDCS-working memory (DCS-WM), tDCS-control cognitive training (DCS-CC), and sham tDCS-working memory (WM-CD) groups. The primary outcome would be working memory test - the n-back task performance and the Chinese version of the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog). Secondary outcomes would be test performance of specific cognitive domains and mood. Intention-to-treat analysis would be carried out. Changes of efficacy indicators with time and intervention would be tested with mixed effect models. This study adopts the theory of neuroplasticity to evaluate the potential cognitive benefits of non-invasive electrical brain stimulation, working memory training and dual stimulation in older adults at risk of cognitive decline. It would also examine the tolerability, program adherence and adverse effects of this novel intervention. Information would be helpful for further research of dementia prevention studies. ChiCTR-TRC- 14005036 Date of registration: 31 July 2014.

The Role of Celestial Compass Information in Cataglyphis Ants during Learning Walks and for Neuroplasticity in the Central Complex and Mushroom Bodies

PubMed Central

Grob, Robin; Fleischmann, Pauline N.; Grübel, Kornelia; Wehner, Rüdiger; Rössler, Wolfgang

2017-01-01

Central place foragers are faced with the challenge to learn the position of their nest entrance in its surroundings, in order to find their way back home every time they go out to search for food. To acquire navigational information at the beginning of their foraging career, Cataglyphis noda performs learning walks during the transition from interior worker to forager. These small loops around the nest entrance are repeatedly interrupted by strikingly accurate back turns during which the ants stop and precisely gaze back to the nest entrance—presumably to learn the landmark panorama of the nest surroundings. However, as at this point the complete navigational toolkit is not yet available, the ants are in need of a reference system for the compass component of the path integrator to align their nest entrance-directed gazes. In order to find this directional reference system, we systematically manipulated the skylight information received by ants during learning walks in their natural habitat, as it has been previously suggested that the celestial compass, as part of the path integrator, might provide such a reference system. High-speed video analyses of distinct learning walk elements revealed that even exclusion from the skylight polarization pattern, UV-light spectrum and the position of the sun did not alter the accuracy of the look back to the nest behavior. We therefore conclude that C. noda uses a different reference system to initially align their gaze directions. However, a comparison of neuroanatomical changes in the central complex and the mushroom bodies before and after learning walks revealed that exposure to UV light together with a naturally changing polarization pattern was essential to induce neuroplasticity in these high-order sensory integration centers of the ant brain. This suggests a crucial role of celestial information, in particular a changing polarization pattern, in initially calibrating the celestial compass system. PMID:29184487

The Role of Celestial Compass Information in Cataglyphis Ants during Learning Walks and for Neuroplasticity in the Central Complex and Mushroom Bodies.

PubMed

Grob, Robin; Fleischmann, Pauline N; Grübel, Kornelia; Wehner, Rüdiger; Rössler, Wolfgang

2017-01-01

Central place foragers are faced with the challenge to learn the position of their nest entrance in its surroundings, in order to find their way back home every time they go out to search for food. To acquire navigational information at the beginning of their foraging career, Cataglyphis noda performs learning walks during the transition from interior worker to forager. These small loops around the nest entrance are repeatedly interrupted by strikingly accurate back turns during which the ants stop and precisely gaze back to the nest entrance-presumably to learn the landmark panorama of the nest surroundings. However, as at this point the complete navigational toolkit is not yet available, the ants are in need of a reference system for the compass component of the path integrator to align their nest entrance-directed gazes. In order to find this directional reference system, we systematically manipulated the skylight information received by ants during learning walks in their natural habitat, as it has been previously suggested that the celestial compass, as part of the path integrator, might provide such a reference system. High-speed video analyses of distinct learning walk elements revealed that even exclusion from the skylight polarization pattern, UV-light spectrum and the position of the sun did not alter the accuracy of the look back to the nest behavior. We therefore conclude that C. noda uses a different reference system to initially align their gaze directions. However, a comparison of neuroanatomical changes in the central complex and the mushroom bodies before and after learning walks revealed that exposure to UV light together with a naturally changing polarization pattern was essential to induce neuroplasticity in these high-order sensory integration centers of the ant brain. This suggests a crucial role of celestial information, in particular a changing polarization pattern, in initially calibrating the celestial compass system.

Secondhand tobacco smoke exposure differentially alters nucleus tractus solitarius neurons at two different ages in developing non-human primates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sekizawa, Shin-ichi, E-mail: ssekizawa@ucdavis.ed; Joad, Jesse P.; Pinkerton, Kent E.

Exposing children to secondhand tobacco smoke (SHS) is associated with increased risk for asthma, bronchiolitis and SIDS. The role for changes in the developing CNS contributing to these problems has not been fully explored. We used rhesus macaques to test the hypothesis that SHS exposure during development triggers neuroplastic changes in the nucleus tractus solitarius (NTS), where lung sensory information related to changes in airway and lung function is first integrated. Pregnant monkeys were exposed to filtered air (FA) or SHS for 6 h/day, 5 days/week starting at 50-day gestational age. Mother/infant pairs continued the exposures postnatally to age 3more » or 13 months, which may be equivalent to approximately 1 or 4 years of human age, respectively. Whole-cell recordings were made of second-order NTS neurons in transverse brainstem slices. To target the consequences of SHS exposure based on neuronal subgroups, we classified NTS neurons into two phenotypes, rapid-onset spiking (RS) and delayed-onset spiking (DS), and then evaluated intrinsic and synaptic excitabilities in FA-exposed animals. RS neurons showed greater cell excitability especially at age of 3 months while DS neurons received greater amplitudes of excitatory postsynaptic currents (EPSCs). Developmental neuroplasticity such as increases in intrinsic and synaptic excitabilities were detected especially in DS neurons. In 3 month olds, SHS exposure effects were limited to excitatory changes in RS neurons, specifically increases in evoked EPSC amplitudes and increased spiking responses accompanied by shortened action potential width. By 13 months, the continued SHS exposure inhibited DS neuronal activity; decreases in evoked EPSC amplitudes and blunted spiking responses accompanied by prolonged action potential width. The influence of SHS exposure on age-related and phenotype specific changes may be associated with age-specific respiratory problems, for which SHS exposure can increase the risk, such as SIDS and bronchiolitis in infants and asthma in older children.« less

Reduced hippocampal N-acetyl-aspartate (NAA) as a biomarker for overweight☆

PubMed Central

Coplan, Jeremy D.; Fathy, Hassan M.; Abdallah, Chadi G.; Ragab, Sherif A.; Kral, John G.; Mao, Xiangling; Shungu, Dikoma C.; Mathew, Sanjay J.

2014-01-01

Objective We previously demonstrated an inverse relationship between both dentate gyrus neurogenesis – a form of neuroplasticity – and expression of the antiapoptotic gene marker, BCL-2 and adult macaque body weight. We therefore explored whether a similar inverse correlation existed in humans between body mass index (BMI) and hippocampal N-acetyl-aspartate (NAA), a marker of neuronal integrity and putatively, neuroplasticity. We also studied the relationship of a potentially neurotoxic process, worry, to hippocampal NAA in patients with generalized anxiety disorder (GAD) and control subjects (CS). Methods We combined two previously studied cohorts of GAD and control subjects. Using proton magnetic resonance spectroscopy imaging (1H MRSI) in medication-free patients with GAD (n = 29) and a matched healthy control group (n = 22), we determined hippocampal concentrations of (1) NAA (2) choline containing compounds (CHO), and (3) Creatine + phosphocreatine (CR). Data were combined from 1.5 T and 3 T scans by converting values from each cohort to z-scores. Overweight and GAD diagnosis were used as categorical variables while the Penn State Worry Questionnaire (PSWQ) and Anxiety Sensitivity Index (ASI) were used as dependent variables. Results Overweight subjects (BMI ≥ 25) exhibited lower NAA levels in the hippocampus than normal-weight subjects (BMI < 25) (partial Eta-squared = 0.14) controlling for age, sex and psychiatric diagnosis, and the effect was significant for the right hippocampus in both GAD patients and control subjects. An inverse linear correlation was noted in all subjects between right hippocampal NAA and BMI. High scores on the PSWQ predicted low hippocampal NAA and CR. Both BMI and worry were independent inverse predictors of hippocampal NAA. Conclusion Overweight was associated with reduced NAA concentrations in the hippocampus with a strong effect size. Future mechanistic studies are warranted. PMID:24501701

Corticotrigeminal Projections from the Insular Cortex to the Trigeminal Caudal Subnucleus Regulate Orofacial Pain after Nerve Injury via Extracellular Signal-Regulated Kinase Activation in Insular Cortex Neurons.

PubMed

Wang, Jian; Li, Zhi-Hua; Feng, Ban; Zhang, Ting; Zhang, Han; Li, Hui; Chen, Tao; Cui, Jing; Zang, Wei-Dong; Li, Yun-Qing

2015-01-01

Cortical neuroplasticity alterations are implicated in the pathophysiology of chronic orofacial pain. However, the relationship between critical cortex excitability and orofacial pain maintenance has not been fully elucidated. We recently demonstrated a top-down corticospinal descending pain modulation pathway from the anterior cingulate cortex (ACC) to the spinal dorsal horn that could directly regulate nociceptive transmission. Thus, we aimed to investigate possible corticotrigeminal connections that directly influence orofacial nociception in rats. Infraorbital nerve chronic constriction injury (IoN-CCI) induced significant orofacial nociceptive behaviors as well as pain-related negative emotions such as anxiety/depression in rats. By combining retrograde and anterograde tract tracing, we found powerful evidence that the trigeminal caudal subnucleus (Vc), especially the superficial laminae (I/II), received direct descending projections from granular and dysgranular parts of the insular cortex (IC). Extracellular signal-regulated kinase (ERK), an important signaling molecule involved in neuroplasticity, was significantly activated in the IC following IoN-CCI. Moreover, in IC slices from IoN-CCI rats, U0126, an inhibitor of ERK activation, decreased both the amplitude and the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and reduced the paired-pulse ratio (PPR) of Vc-projecting neurons. Additionally, U0126 also reduced the number of action potentials in the Vc-projecting neurons. Finally, intra-IC infusion of U0126 obviously decreased Fos expression in the Vc, accompanied by the alleviation of both nociceptive behavior and negative emotions. Thus, the corticotrigeminal descending pathway from the IC to the Vc could directly regulate orofacial pain, and ERK deactivation in the IC could effectively alleviate neuropathic pain as well as pain-related negative emotions in IoN-CCI rats, probably through this top-down pathway. These findings may help researchers and clinicians to better understand the underlying modulation mechanisms of orofacial neuropathic pain and indicate a novel mechanism of ERK inhibitor-induced analgesia.

Imaging the neuroplastic effects of ketamine with VBM and the necessity of placebo control.

PubMed

Höflich, A; Ganger, S; Tik, M; Hahn, A; Kranz, G S; Vanicek, T; Spies, M; Kraus, C; Windischberger, C; Kasper, S; Winkler, D; Lanzenberger, R

2017-02-15

In the last years a plethora of studies have investigated morphological changes induced by behavioural or pharmacological interventions using structural T1-weighted MRI and voxel-based morphometry (VBM). Ketamine is thought to exert its antidepressant action by restoring neuroplasticity. In order to test for acute impact of a single ketamine infusion on grey matter volume we performed a placebo-controlled, double-blind investigation in healthy volunteers using VBM. 28 healthy individuals underwent two MRI sessions within a timeframe of 2 weeks, each consisting of two structural T1-weighted MRIs within a single session, one before and one 45min after infusion of S-ketamine (bolus of 0.11mg/kg, followed by an maintenance infusion of 0.12mg/kg) or placebo (0.9% NaCl infusion) using a crossover design. In the repeated-measures ANOVA with time (post-infusion/pre-infusion) and medication (placebo/ketamine) as factors, no significant effect of interaction and no effect of medication was found (FWE-corrected). Importantly, further post-hoc t-tests revealed a strong "decrease" of grey matter both in the placebo and the ketamine condition over time. This effect was evident mainly in frontal and temporal regions bilaterally with t-values ranging from 4.95 to 5.31 (FWE-corrected at p<0.05 voxel level). The vulnerabilities of VBM have been repeatedly demonstrated, with reports of influence of blood flow, tissue water and direct effects of pharmacological compounds on the MRI signal. Here again, we highlight that the relationship between intervention and VBM results is apparently subject to a number of physiological influences, which are partly unknown. Future studies focusing on the effects of ketamine on grey matter should try to integrate known influential factors such as blood flow into analysis. Furthermore, the results of this study highlight the importance of a carefully performed placebo condition in pharmacological fMRI studies. Copyright © 2016 Elsevier Inc. All rights reserved.

Assessment and manifestation of central sensitisation across different chronic pain conditions.

PubMed

Arendt-Nielsen, L; Morlion, B; Perrot, S; Dahan, A; Dickenson, A; Kress, H G; Wells, C; Bouhassira, D; Mohr Drewes, A

2018-02-01

Different neuroplastic processes can occur along the nociceptive pathways and may be important in the transition from acute to chronic pain and for diagnosis and development of optimal management strategies. The neuroplastic processes may result in gain (sensitisation) or loss (desensitisation) of function in relation to the incoming nociceptive signals. Such processes play important roles in chronic pain, and although the clinical manifestations differ across condition processes, they share some common mechanistic features. The fundamental understanding and quantitative assessment of particularly some of the central sensitisation mechanisms can be translated from preclinical studies into the clinic. The clinical perspectives are implementation of such novel information into diagnostics, mechanistic phenotyping, prevention, personalised treatment, and drug development. The aims of this paper are to introduce and discuss (1) some common fundamental central pain mechanisms, (2) how they may translate into the clinical signs and symptoms across different chronic pain conditions, (3) how to evaluate gain and loss of function using quantitative pain assessment tools, and (4) the implications for optimising prevention and management of pain. The chronic pain conditions selected for the paper are neuropathic pain in general, musculoskeletal pain (chronic low back pain and osteoarthritic pain in particular), and visceral pain (irritable bowel syndrome in particular). The translational mechanisms addressed are local and widespread sensitisation, central summation, and descending pain modulation. Central sensitisation is an important manifestation involved in many different chronic pain conditions. Central sensitisation can be different to assess and evaluate as the manifestations vary from pain condition to pain condition. Understanding central sensitisation may promote better profiling and diagnosis of pain patients and development of new regimes for mechanism based therapy. Some of the mechanisms underlying central sensitisation can be translated from animals to humans providing new options in development of therapies and profiling drugs under development. © 2017 European Pain Federation - EFIC®.

Profiling Coping Strategies in Male and Female Rats: Potential neurobehavioral markers of increased resilience to depressive symptoms

PubMed Central

Kent, Molly; Bardi, Massimo; Hazelgrove, Ashley; Sewell, Kaitlyn; Kirk, Emily; Thompson, Brooke; Trexler, Kristen; Terhune-Cotter, Brennan; Lambert, Kelly

2018-01-01

Coping strategies have been associated with differential stress responsivity, perhaps providing a valuable neurobiological marker for susceptibility to the emergence of depressogenic symptoms or vulnerability to other anxiety-related disorders. Rats profiled with a flexible coping phenotype, for example, exhibit increased neurobiological markers of emotional regulation compared to active and passive copers (Bardi et al., 2012; Lambert et al., 2014). In the current study, responses of male and female rats to prediction errors in a spatial foraging task (dry land maze; DLM) were examined after animals were exposed to chronic unpredictable stress (CUS). Brains were processed following the DLM training/assessment for fos-activation patterns and several measures of neuroplasticity in relevant areas. Behavioral responses observed during both the CUS and DLM phases of testing suggested that males and females employ different means of gathering information such as increased ambulatory exploration in males and rear responses in females. Fecal samples collected during baseline and following CUS swim exposure revealed higher corticosterone (CORT) in active copers, whereas flexible copers had higher dehydroepiandrosterone (DHEA) and DHEA/CORT ratios, both indications of enhanced emotional regulation. Focusing on the neural analysis, flexible copers exhibited fewer fos-immunoreactive cells in the basolateral amygdala and a trend toward lower activation in the insula while encountering the prediction error associated with the DLM probe trial. Coping profiles also differentially influenced markers of neuroplasticity; specifically, flexible copers exhibited higher levels nestin-immunoreactivity (ir). Further, less hippocampal glucocorticoid receptor-ir was observed in the flexible copers than the active and passive copers. In sum, flexible coping rats exhibited evidence of emotional resilience as indicated by several neurobiological measures; however, despite increased rates of depression and related symptoms reported in human females, sex effects weren’t as pervasive as coping strategy profiles in the analysis of neurobiological markers employed in the current study. PMID:28755980

Priming theta burst stimulation enhances motor cortex plasticity in young but not old adults.

PubMed

Opie, George M; Vosnakis, Eleni; Ridding, Michael C; Ziemann, Ulf; Semmler, John G

Primary motor cortex neuroplasticity is reduced in old adults, which may contribute to the motor deficits commonly observed in the elderly. Previous research in young subjects suggests that the neuroplastic response can be enhanced using non-invasive brain stimulation (NIBS), with a larger plastic response observed following priming with both long-term potentiation (LTP) and depression (LTD)-like protocols. However, it is not known if priming stimulation can also modulate plasticity in older adults. To investigate if priming NIBS can be used to modulate motor cortical plasticity in old subjects. In 16 young (22.3 ± 1.0 years) and 16 old (70.2 ± 1.7 years) subjects, we investigated the response to intermittent theta burst stimulation (iTBS; LTP-like) when applied 10 min after sham stimulation, continuous TBS (cTBS; LTD-like) or an identical block of iTBS. Corticospinal plasticity was assessed by recording changes in motor evoked potential (MEP) amplitude. In young subjects, priming with cTBS (cTBS + iTBS) resulted in larger MEPs than priming with either iTBS (iTBS + iTBS; P = 0.001) or sham (sham + iTBS; P < 0.0001), while larger MEPs were seen following iTBS + iTBS than sham + iTBS (P < 0.0001). In old subjects, the response to iTBS + iTBS was not different to sham + iTBS (P > 0.9), whereas the response to cTBS + iTBS was reduced relative to iTBS + iTBS (P = 0.02) and sham + iTBS (P = 0.04). Priming TBS is ineffective for modifying M1 plasticity in older adults, which may limit the therapeutic use of priming stimulation in neurological conditions common in the elderly. Copyright © 2017 Elsevier Inc. All rights reserved.

BDNF-Val66Met-Polymorphism Impact on Cortical Plasticity in Schizophrenia Patients: A Proof-of-Concept Study

PubMed Central

Nitsche, Michael A.; Wobrock, Thomas; Bunse, Tilmann; Rein, Bettina; Herrmann, Maximiliane; Schmitt, Andrea; Nieratschker, Vanessa; Witt, Stephanie H.; Rietschel, Marcella; Falkai, Peter; Hasan, Alkomiet

2015-01-01

Background: Brain-derived neurotrophic factor (BDNF) has been shown to be a moderator of neuroplasticity. A frequent BDNF-polymorphism (Val66Met) is associated with impairments of cortical plasticity. In patients with schizophrenia, reduced neuroplastic responses following non-invasive brain stimulation have been reported consistently. Various studies have indicated a relationship between the BDNF-Val66Met-polymorphism and motor-cortical plasticity in healthy individuals, but schizophrenia patients have yet to be investigated. The aim of this proof-of-concept study was, therefore, to test the impact of the BDNF-Val66Met-polymorphism on inhibitory and facilitatory cortical plasticity in schizophrenia patients. Methods: Cortical plasticity was investigated in 22 schizophrenia patients and 35 healthy controls using anodal and cathodal transcranial direct-current stimulation (tDCS) applied to the left primary motor cortex. Animal and human research indicates that excitability shifts following anodal and cathodal tDCS are related to molecular long-term potentiation and long-term depression. To test motor-cortical excitability before and after tDCS, well-established single- and paired-pulse transcranial magnetic stimulation protocols were applied. Results: Our analysis revealed increased glutamate-mediated intracortical facilitation in met-heterozygotes compared to val-homozygotes at baseline. Following cathodal tDCS, schizophrenia met-heterozygotes had reduced gamma-amino-butyric-acid-mediated short-interval intracortical inhibition, whereas healthy met-heterozygotes displayed the opposite effect. The BDNF-Val66Met-polymorphism did not influence single-pulse motor-evoked potential amplitudes after tDCS. Conclusions: These preliminary findings support the notion of an association of the BDNF-Val66Met-polymorphism with observable alterations in plasticity following cathodal tDCS in schizophrenia patients. This indicates a complex interaction between inhibitory intracortical interneuron-networks, cortical plasticity, and the BDNF-Val66Met-polymorphism. Further replication and validation need to be dedicated to this question to confirm this relationship. PMID:25612896

Secondhand tobacco smoke exposure differentially alters nucleus tractus solitarius neurons at two different ages in developing non-human primates.

PubMed

Sekizawa, Shin-Ichi; Joad, Jesse P; Pinkerton, Kent E; Bonham, Ann C

2010-01-15

Exposing children to secondhand tobacco smoke (SHS) is associated with increased risk for asthma, bronchiolitis and SIDS. The role for changes in the developing CNS contributing to these problems has not been fully explored. We used rhesus macaques to test the hypothesis that SHS exposure during development triggers neuroplastic changes in the nucleus tractus solitarius (NTS), where lung sensory information related to changes in airway and lung function is first integrated. Pregnant monkeys were exposed to filtered air (FA) or SHS for 6 h/day, 5 days/week starting at 50-day gestational age. Mother/infant pairs continued the exposures postnatally to age 3 or 13 months, which may be equivalent to approximately 1 or 4 years of human age, respectively. Whole-cell recordings were made of second-order NTS neurons in transverse brainstem slices. To target the consequences of SHS exposure based on neuronal subgroups, we classified NTS neurons into two phenotypes, rapid-onset spiking (RS) and delayed-onset spiking (DS), and then evaluated intrinsic and synaptic excitabilities in FA-exposed animals. RS neurons showed greater cell excitability especially at age of 3 months while DS neurons received greater amplitudes of excitatory postsynaptic currents (EPSCs). Developmental neuroplasticity such as increases in intrinsic and synaptic excitabilities were detected especially in DS neurons. In 3 month olds, SHS exposure effects were limited to excitatory changes in RS neurons, specifically increases in evoked EPSC amplitudes and increased spiking responses accompanied by shortened action potential width. By 13 months, the continued SHS exposure inhibited DS neuronal activity; decreases in evoked EPSC amplitudes and blunted spiking responses accompanied by prolonged action potential width. The influence of SHS exposure on age-related and phenotype specific changes may be associated with age-specific respiratory problems, for which SHS exposure can increase the risk, such as SIDS and bronchiolitis in infants and asthma in older children.

Blockade of arginine vasotocin signaling reduces aggressive behavior and c-Fos expression in the preoptic area and periventricular nucleus of the posterior tuberculum in male Amphiprion ocellaris.

PubMed

Yaeger, C; Ros, A M; Cross, V; Deangelis, R S; Stobaugh, D J; Rhodes, J S

2014-05-16

Many marine fishes change sex in response to social cues when the dominance hierarchy is perturbed. Arginine-vasotocin (AVT) and the mammalian homolog arginine vasopressin are neuropeptides involved in social and reproductive behaviors across vertebrate taxa. The goal of this study was to determine whether AVT signaling influences aggression and expression of c-Fos, a marker of neuroplasticity, in key brain regions of the social decision circuit in Amphiprion ocellaris clownfish, a species where behavioral dominance precedes gonadal sex change from male to female. In experiment 1, juvenile clownfish (average mass 2.5g) were paired together in a tank (a total of 24 pairs), matched approximately for size with one fish randomly receiving either an intraperitoneal injection of the arginine vasopressin V1a receptor antagonist (Manning compound) or saline vehicle, and evaluated for aggressive and submissive behaviors over a 10-min period. The second experiment was a repeat of the first using five pairs of mature, reproductive males, except the animals interacted for 90-min immediately followed by euthanasia for immunohistochemical detection of c-Fos protein. Numbers of c-Fos-positive cells were quantified in the preoptic area of the hypothalamus (POA), the anterior tuberal nucleus (aTn), and periventricular nucleus of the posterior tuberculum (TPp). Manning compound significantly reduced aggression and the probability of winning the contest relative to saline (vehicle) controls. In experiment 2, saline-treated fish displayed approximately twice as many c-Fos-positive cells in the POA and 25% more in the TPp than the Manning-treated fish, no differences were observed in the aTn. Taken together, results suggest AVT signaling is necessary for aggressive behavior and expression of neuroplasticity in the POA and TPp that likely contributes to behavioral dominance and hence, sex change in A. ocellaris. Published by Elsevier Ltd.

Computer Enabled Neuroplasticity Treatment: A Clinical Trial of a Novel Design for Neurofeedback Therapy in Adult ADHD

PubMed Central

Cowley, Benjamin; Holmström, Édua; Juurmaa, Kristiina; Kovarskis, Levas; Krause, Christina M.

2016-01-01

Background: We report a randomized controlled clinical trial of neurofeedback therapy intervention for ADHD/ADD in adults. We focus on internal mechanics of neurofeedback learning, to elucidate the primary role of cortical self-regulation in neurofeedback. We report initial results; more extensive analysis will follow. Methods: Trial has two phases: intervention and follow-up. The intervention consisted of neurofeedback treatment, including intake and outtake measurements, using a waiting-list control group. Treatment involved ~40 h-long sessions 2–5 times per week. Training involved either theta/beta or sensorimotor-rhythm regimes, adapted by adding a novel “inverse-training” condition to promote self-regulation. Follow-up (ongoing) will consist of self-report and executive function tests. Setting: Intake and outtake measurements were conducted at University of Helsinki. Treatment was administered at partner clinic Mental Capital Care, Helsinki. Randomization: We randomly allocated half the sample then adaptively allocated the remainder to minimize baseline differences in prognostic variables. Blinding: Waiting-list control design meant trial was not blinded. Participants: Fifty-four adult Finnish participants (mean age 36 years; 29 females) were recruited after screening by psychiatric review. Forty-four had ADHD diagnoses, 10 had ADD. Measurements: Symptoms were assessed by computerized attention test (T.O.V.A.) and self-report scales, at intake and outtake. Performance during neurofeedback trials was recorded. Results: Participants were recruited and completed intake measurements during summer 2012, before assignment to treatment and control, September 2012. Outtake measurements ran April-August 2013. After dropouts, 23 treatment and 21 waiting-list participants remained for analysis. Initial analysis showed that, compared to waiting-list control, neurofeedback promoted improvement of self-reported ADHD symptoms, but did not show transfer of learning to T.O.V.A. Comprehensive analysis will be reported elsewhere. Trial Registration: “Computer Enabled Neuroplasticity Treatment (CENT),” ISRCTN13915109. PMID:27242472

Dose-Related Target Occupancy and Effects on Circuitry, Behavior, and Neuroplasticity of the Glycine Transporter-1 Inhibitor PF-03463275 in Healthy and Schizophrenia Subjects.

PubMed

D'Souza, Deepak Cyril; Carson, Richard E; Driesen, Naomi; Johannesen, Jason; Ranganathan, Mohini; Krystal, John H

2018-01-31

Glycine transporter-1 (GlyT1) inhibitors may ameliorate cognitive impairments associated with schizophrenia. The dose-related occupancy and target engagement of the GlyT1 inhibitor PF-03463275 were studied to inform optimal dose selection for a clinical trial for cognitive impairments associated with schizophrenia. In substudy 1, the effects of PF-03463275 (10, 20, and 40 mg twice a day) on occupancy of GlyT1 were tested using positron emission tomography and 18 F-MK-6577, and visual long-term potentiation (LTP) in schizophrenia patients (SZs) and healthy control subjects. Furthermore, the capacity of PF-03463275 to attenuate ketamine-induced disruption of working memory-related activation of a "working memory" circuit was tested only in healthy control subjects using functional magnetic resonance imaging. Subsequently, the effects of PF-03463275 (60 mg twice a day) on occupancy of GlyT1 and long-term potentiation were examined only in SZs (substudy 2). PF-03463275 at 10, 20, 40, and 60 mg twice a day produced ∼44%, 61%, 76%, and 83% GlyT1 occupancy, respectively, in SZs with higher ligand binding to GlyT1 in subcortical versus cortical regions. PF-03463275 did not attenuate any ketamine-induced effects but did improve working memory accuracy in healthy control subjects. PF-03463275 increased long-term potentiation only in SZs with peak effects at 40 mg twice a day (∼75% GlyT1 occupancy) and with a profile suggestive of an inverted U dose response. PF-03463275 was well-tolerated. The dose-related GlyT1 occupancy of PF-03463275 is linear. While PF-03463275 did not show evidence of facilitating N-methyl-D-aspartate receptor function in the ketamine assay, it enhanced neuroplasticity in SZs. These findings provide support for a clinical trial to test the ability of PF-03463275 to enhance cognitive remediation toward addressing cognitive impairments associated with schizophrenia. Published by Elsevier Inc.

Short Meditation Trainings Enhance Non-REM Sleep Low-Frequency Oscillations

PubMed Central

Dentico, Daniela; Ferrarelli, Fabio; Riedner, Brady A.; Smith, Richard; Zennig, Corinna; Lutz, Antoine; Tononi, Giulio; Davidson, Richard J.

2016-01-01

Study Objectives We have recently shown higher parietal-occipital EEG gamma activity during sleep in long-term meditators compared to meditation-naive individuals. This gamma increase was specific for NREM sleep, was present throughout the entire night and correlated with meditation expertise, thus suggesting underlying long-lasting neuroplastic changes induced through prolonged training. The aim of this study was to explore the neuroplastic changes acutely induced by 2 intensive days of different meditation practices in the same group of practitioners. We also repeated baseline recordings in a meditation-naive cohort to account for time effects on sleep EEG activity. Design High-density EEG recordings of human brain activity were acquired over the course of whole sleep nights following intervention. Setting Sound-attenuated sleep research room. Patients or Participants Twenty-four long-term meditators and twenty-four meditation-naïve controls. Interventions Two 8-h sessions of either a mindfulness-based meditation or a form of meditation designed to cultivate compassion and loving kindness, hereafter referred to as compassion meditation. Measurements and Results We found an increase in EEG low-frequency oscillatory activities (1–12 Hz, centered around 7–8 Hz) over prefrontal and left parietal electrodes across whole night NREM cycles. This power increase peaked early in the night and extended during the third cycle to high-frequencies up to the gamma range (25–40 Hz). There was no difference in sleep EEG activity between meditation styles in long-term meditators nor in the meditation naïve group across different time points. Furthermore, the prefrontal-parietal changes were dependent on meditation life experience. Conclusions This low-frequency prefrontal-parietal activation likely reflects acute, meditation-related plastic changes occurring during wakefulness, and may underlie a top-down regulation from frontal and anterior parietal areas to the posterior parietal and occipital regions showing chronic, long-lasting plastic changes in long-term meditators. PMID:26900914

Fluoxetine Exerts Age-Dependent Effects on Behavior and Amygdala Neuroplasticity in the Rat

PubMed Central

Homberg, Judith R.; Olivier, Jocelien D. A.; Blom, Tom; Arentsen, Tim; van Brunschot, Chantal; Schipper, Pieter; Korte-Bouws, Gerdien; van Luijtelaar, Gilles; Reneman, Liesbeth

2011-01-01

The selective serotonin reuptake inhibitor (SSRI) Prozac® (fluoxetine) is the only registered antidepressant to treat depression in children and adolescents. Yet, while the safety of SSRIs has been well established in adults, serotonin exerts neurotrophic actions in the developing brain and thereby may have harmful effects in adolescents. Here we treated adolescent and adult rats chronically with fluoxetine (12 mg/kg) at postnatal day (PND) 25 to 46 and from PND 67 to 88, respectively, and tested the animals 7–14 days after the last injection when (nor)fluoxetine in blood plasma had been washed out, as determined by HPLC. Plasma (nor)fluoxetine levels were also measured 5 hrs after the last fluoxetine injection, and matched clinical levels. Adolescent rats displayed increased behavioral despair in the forced swim test, which was not seen in adult fluoxetine treated rats. In addition, beneficial effects of fluoxetine on wakefulness as measured by electroencephalography in adults was not seen in adolescent rats, and age-dependent effects on the acoustic startle response and prepulse inhibition were observed. On the other hand, adolescent rats showed resilience to the anorexic effects of fluoxetine. Exploratory behavior in the open field test was not affected by fluoxetine treatment, but anxiety levels in the elevated plus maze test were increased in both adolescent and adult fluoxetine treated rats. Finally, in the amygdala, but not the dorsal raphe nucleus and medial prefrontal cortex, the number of PSA-NCAM (marker for synaptic remodeling) immunoreactive neurons was increased in adolescent rats, and decreased in adult rats, as a consequence of chronic fluoxetine treatment. No fluoxetine-induced changes in 5-HT1A receptor immunoreactivity were observed. In conclusion, we show that fluoxetine exerts both harmful and beneficial age-dependent effects on depressive behavior, body weight and wakefulness, which may relate, in part, to differential fluoxetine-induced neuroplasticity in the amygdala. PMID:21304948

A Key Role for Nectin-1 in the Ventral Hippocampus in Contextual Fear Memory

PubMed Central

Grosse, Jocelyn; Krummenacher, Claude; Sandi, Carmen

2013-01-01

Nectins are cell adhesion molecules that are widely expressed in the brain. Nectin expression shows a dynamic spatiotemporal regulation, playing a role in neural migratory processes during development. Nectin-1 and nectin-3 and their heterophilic trans-interactions are important for the proper formation of synapses. In the hippocampus, nectin-1 and nectin-3 localize at puncta adherentia junctions and may play a role in synaptic plasticity, a mechanism essential for memory and learning. We evaluated the potential involvement of nectin-1 and nectin-3 in memory consolidation using an emotional learning paradigm. Rats trained for contextual fear conditioning showed transient nectin-1—but not nectin-3—protein upregulation in synapse-enriched hippocampal fractions at about 2 h posttraining. The upregulation of nectin-1 was found exclusively in the ventral hippocampus and was apparent in the synaptoneurosomal fraction. This upregulation was induced by contextual fear conditioning but not by exposure to context or shock alone. When an antibody against nectin-1, R165, was infused in the ventral-hippocampus immediately after training, contextual fear memory was impaired. However, treatment with the antibody in the dorsal hippocampus had no effect in contextual fear memory formation. Similarly, treatment with the antibody in the ventral hippocampus did not interfere with acoustic memory formation. Further control experiments indicated that the effects of ventral hippocampal infusion of the nectin-1 antibody in contextual fear memory cannot be ascribed to memory non-specific effects such as changes in anxiety-like behavior or locomotor behavior. Therefore, we conclude that nectin-1 recruitment to the perisynaptic environment in the ventral hippocampus plays an important role in the formation of contextual fear memories. Our results suggest that these mechanisms could be involved in the connection of emotional and contextual information processed in the amygdala and dorsal hippocampus, respectively, thus opening new venues for the development of treatments to psychopathological alterations linked to impaired contextualization of emotions. PMID:23418609

Loss of dysbindin-1, a risk gene for schizophrenia, leads to impaired group 1 metabotropic glutamate receptor function in mice

PubMed Central

Bhardwaj, Sanjeev K.; Ryan, Richard T.; Wong, Tak Pan; Srivastava, Lalit K.

2015-01-01

The expression of dysbindin-1, a protein coded by the risk gene dtnbp1, is reduced in the brains of schizophrenia patients. Evidence indicates a role of dysbindin-1 in dopaminergic and glutamatergic transmission. Glutamatergic transmission and plasticity at excitatory synapses is critically regulated by G-protein coupled metabotropic glutamate receptor (mGluR) family members, that have been implicated in schizophrenia. Here, we report a role of dysbindin-1 in hippocampal group 1 mGluR (mGluRI) function in mice. In hippocampal synaptoneurosomal preparations from sandy (sdy) mice, that have a loss of function mutation in dysbindin-1 gene, we observed a striking reduction in mGluRI agonist [(S)-3, 5-dihydroxyphenylglycine] (DHPG)-induced phosphorylation of extracellular signal regulated kinase 1/2 (ERK1/2). This mGluR-ERK1/2 deficit occurred in the absence of significant changes in protein levels of the two members of the mGluRI family (i.e., mGluR1 and mGluR5) or in another mGluRI signaling pathway, i.e., protein kinase C (PKC). Aberrant mGluRI-ERK1/2 signaling affected hippocampal synaptic plasticity in the sdy mutants as DHPG-induced long-term depression (LTD) at CA1 excitatory synapses was significantly reduced. Behavioral data suggest that the mGluRI hypofunction may underlie some of the cognitive abnormalities described in sdy mice as the administration of CDPPB (3-cyano-N-(1, 3-diphenyl-1H-pyrazol-5-yl benzamide), a positive allosteric modulator of mGluR5, rescued short-term object recognition and spatial learning and memory deficits in these mice. Taken together, our data suggest a novel role of dysbindin-1 in regulating mGluRI functions. PMID:25859193

Inhibition of GABA-gated chloride channels by 12,14-dichlorodehydroabietic acid in mammalian brain

PubMed Central

Nicholson, Russell A; Lees, George; Zheng, Jian; Verdon, Bernard

1999-01-01

12,14-dichlorodehydroabietic acid (12,14-Cl2DHA) reduced GABA-stimulated uptake of 36Cl− into mouse brain synaptoneurosomes suggesting inhibition of mammalian GABAA receptor function. 12,14-Cl2DHA did not affect the binding of [3H]-muscimol to brain membranes but displaced specifically bound [3H]-EBOB. The inhibitory effect on [3H]-EBOB binding was not reversible. 12,14-Cl2DHA reduced the availability of [3H]-EBOB binding sites (Bmax) without changing the KD of the radioligand for remaining sites. 12,14-Cl2DHA did not affect the rate of association of [3H]-EBOB with its chloride channel receptor, but increased the initial rate of [3H]-EBOB dissociation. 12,14-Cl2DHA enhanced the incidence of EPSCs when rapidly applied to cultured rat cortical neurones. Longer exposures produced block of IPSCs with marked increases in the frequency of EPSCs and min EPSCs. 12,14-Cl2DHA also irreversibly suppressed chloride currents evoked by pulses of exogenous GABA in these cells. Ultimately, 12,14-Cl2DHA inhibited all synaptic traffic and action currents in current clamped cells indicating that, in contrast to picrotoxinin (which causes paroxysmal bursting), it is not fully selective for the GABAA receptor-chloride channel complex. The depolarizing block seen with 12,14-Cl2DHA in amphotericin-perforated preparations implicates loss of Ca2+ buffering in the polarity change and this may account for inhibition of spontaneous action potentials. Our investigation demonstrates that 12,14-Cl2DHA blocks GABA-dependent chloride entry in mammalian brain and operates as a non-competitive insurmountable GABAA antagonist. The mechanism likely involves either irreversible binding of 12,14-Cl2DHA to the trioxabicyclooctane recognition site or a site that is allosterically coupled to it. We cannot exclude, however, the possibility that 12,14-Cl2DHA causes localized proteolysis or more extensive conformational change within a critical subunit of the chloride channel. PMID:10204999

Effect of D-cycloserine in conjunction with fear extinction training on extracellular signal-regulated kinase activation in the medial prefrontal cortex and amygdala in rat.

PubMed

Gupta, Subhash C; Hillman, Brandon G; Prakash, Anand; Ugale, Rajesh R; Stairs, Dustin J; Dravid, Shashank M

2013-06-01

D-cycloserine (DCS) is currently under clinical trials for a number of neuropsychiatric conditions and has been found to augment fear extinction in rodents and exposure therapy in humans. However, the molecular mechanism of DCS action in these multiple modalities remains unclear. Here, we describe the effect of DCS administration, alone or in conjunction with extinction training, on neuronal activity (c-fos) and neuronal plasticity [phospho-extracellular signal-regulated kinase (pERK)] markers using immunohistochemistry. We found that intraperitoneal administration of DCS in untrained young rats (24-28 days old) increased c-fos- and pERK-stained neurons in both the prelimbic and infralimbic division of the medial prefrontal cortex (mPFC) and reduced pERK levels in the lateral nucleus of the central amygdala. Moreover, DCS administration significantly increased GluA1, GluN1, GluN2A, and GluN2B expression in the mPFC. In a separate set of animals, we found that DCS facilitated fear extinction and increased pERK levels in the infralimbic prefrontal cortex, prelimbic prefrontal cortex intercalated cells and lateral nucleus of the central amygdala, compared with saline control. In the synaptoneurosomal preparation, we found that extinction training increased iGluR protein expression in the mPFC, compared with context animals. No significant difference in protein expression was observed between extinction-saline and extinction-DCS groups in the mPFC. In contrast, in the amygdala DCS, the conjunction with extinction training led to an increase in iGluR subunit expression, compared with the extinction-saline group. Our data suggest that the efficacy of DCS in neuropsychiatric disorders may be partly due to its ability to affect neuronal activity and signaling in the mPFC and amygdala subnuclei. © 2013 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

Impaired activity-dependent FMRP translation and enhanced mGluR-dependent LTD in Fragile X premutation mice

PubMed Central

Iliff, Adam J.; Renoux, Abigail J.; Krans, Amy; Usdin, Karen; Sutton, Michael A.; Todd, Peter K.

2013-01-01

Fragile X premutation-associated disorders, including Fragile X-associated Tremor Ataxia Syndrome, result from unmethylated CGG repeat expansions in the 5′ untranslated region (UTR) of the FMR1 gene. Premutation-sized repeats increase FMR1 transcription but impair rapid translation of the Fragile X mental retardation protein (FMRP), which is absent in Fragile X Syndrome (FXS). Normally, FMRP binds to RNA and regulates metabotropic glutamate receptor (mGluR)-mediated synaptic translation, allowing for dendritic synthesis of several proteins. FMRP itself is also synthesized at synapses in response to mGluR activation. However, the role of activity-dependent translation of FMRP in synaptic plasticity and Fragile X-premutation-associated disorders is unknown. To investigate this question, we utilized a CGG knock-in mouse model of the Fragile X premutation with 120–150 CGG repeats in the mouse Fmr1 5′ UTR. These mice exhibit increased Fmr1 mRNA production but impaired FMRP translational efficiency, leading to a modest reduction in basal FMRP expression. Cultured hippocampal neurons and synaptoneurosomes derived from CGG KI mice demonstrate impaired FMRP translation in response to the group I mGluR agonist 3,5-dihydroxyphenylglycine. Electrophysiological analysis reveals enhanced mGluR-mediated long-term depression (mGluR-LTD) at CA3–CA1 synapses in acute hippocampal slices prepared from CGG KI mice relative to wild-type littermates, similar to Fmr1 knockout mice. However, unlike mGluR-LTD in mice completely lacking FMRP, mGluR-LTD in CGG knock-in mice remains dependent on new protein synthesis. These studies demonstrate partially overlapping synaptic plasticity phenotypes in mouse models of FXS and Fragile X premutation disorders and support a role for activity-dependent synthesis of FMRP in enduring forms of synaptic plasticity. PMID:23250915

[Hemisphere dominance of cortical speech processing and its dynamics in the course of aphasia therapy. A psychophysiologic contribution to the discussion of the neuronal plasticity hypothesis].

PubMed

Maier, R; Lünser, W

1991-01-01

Examinations of aphasic patients by using cognitive tasks were based on the hypothesis that semantically evoked potentials correlate to the processing of information in the cortical areas of Broca and Wernicke. Some of the examined right-handed patients with ischemic lesions of the left hemisphere produced characteristic potentials in the right temporal lobe, and not in the dominant left lobe as was expected. These case histories suggest that in these patients speech processing moved into the subdominant hemisphere as a result of compensation after cerebral damage by using the faculty of neuroplasticity. Furthermore an extended classification of aphasias is presented, illustrated by a three-parameter model.