One of the most hotly pursued topics in neuroscience and therapeutic medicine is the use of stem cells in the adult brain. Growing in parallel to this emerging field is the recognition that the adult brain is indeed capable of generating new cells. While neurogenesis was understood to be restricted to a few areas, recent studies suggest that damage to the adult brain can trigger neurogenesis even in regions outside of these specific areas. This finding raises the possibility that neurons born in response to perturbation in the brain may be involved in the recovery of function in the damaged adult brain. The key is understanding how to cultivate these newborn cells, because they do not remain viable if they are not accepted into the damaged network of interconnected neurons which support specific functions. From a birth site, undifferentiated precursor cells or neurons undergo migration and differentiation. Many factors influence the safe journey of migrating cells and their survival after maturation at their destination. This review will present evidence from ring dove studies that an activity-dependent mechanism underlies the survival of adult newborn neurons and establishment of their functionality. This evidence includes: [1] unique electrophysiological properties or specific connectivity associated with various type of neurons involved in ring dove coo behavior and reproductive function, [2] emergence of electrophysiological properties and specific projection neurons emanating from newborn neurons after hypothalamic lesion, and finally [3] collective behavioral analyses of social stimulations suggesting that sensorimotor events contribute to the integration of new neurons and reinstatement of function.
{"title":"Adult Neurogenesis in Injury-Induced Self-Repair: Use It or Lose It.","authors":"Mei-Fang Cheng","doi":"10.3233/BPL-160030","DOIUrl":"10.3233/BPL-160030","url":null,"abstract":"<p><p>One of the most hotly pursued topics in neuroscience and therapeutic medicine is the use of stem cells in the adult brain. Growing in parallel to this emerging field is the recognition that the adult brain is indeed capable of generating new cells. While neurogenesis was understood to be restricted to a few areas, recent studies suggest that damage to the adult brain can trigger neurogenesis even in regions outside of these specific areas. This finding raises the possibility that neurons born in response to perturbation in the brain may be involved in the recovery of function in the damaged adult brain. The key is understanding how to cultivate these newborn cells, because they do not remain viable if they are not accepted into the damaged network of interconnected neurons which support specific functions. From a birth site, undifferentiated precursor cells or neurons undergo migration and differentiation. Many factors influence the safe journey of migrating cells and their survival after maturation at their destination. This review will present evidence from ring dove studies that an activity-dependent mechanism underlies the survival of adult newborn neurons and establishment of their functionality. This evidence includes: [1] unique electrophysiological properties or specific connectivity associated with various type of neurons involved in ring dove coo behavior and reproductive function, [2] emergence of electrophysiological properties and specific projection neurons emanating from newborn neurons after hypothalamic lesion, and finally [3] collective behavioral analyses of social stimulations suggesting that sensorimotor events contribute to the integration of new neurons and reinstatement of function.</p>","PeriodicalId":72451,"journal":{"name":"Brain plasticity (Amsterdam, Netherlands)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/41/70/bpl-2-bpl160030.PMC5928550.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36102055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Davide Guerrieri, Hyo Youl Moon, Henriette van Praag
There is increasing evidence that an active lifestyle benefits both body and brain. However, not everyone may be able to exercise due to disease, injury or aging-related frailty. Identification of cellular targets activated by physical activity may lead to the development of new compounds that can, to some extent, mimic systemic and central effects of exercise. This review will focus on factors relevant to energy metabolism in muscle, such as the 5' adenosine monophosphate-activated protein kinase (AMPK) - sirtuin (SIRT1) - Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) pathway, and the molecules affecting it. In particular, putative exercise-mimetics such as AICAR, metformin, and GW501516 will be discussed. Moreover, plant-derived polyphenols such as resveratrol and (-)epicatechin, with exercise-like effects on the body and brain will be evaluated.
{"title":"Exercise in a Pill: The Latest on Exercise-Mimetics.","authors":"Davide Guerrieri, Hyo Youl Moon, Henriette van Praag","doi":"10.3233/BPL-160043","DOIUrl":"https://doi.org/10.3233/BPL-160043","url":null,"abstract":"<p><p>There is increasing evidence that an active lifestyle benefits both body and brain. However, not everyone may be able to exercise due to disease, injury or aging-related frailty. Identification of cellular targets activated by physical activity may lead to the development of new compounds that can, to some extent, mimic systemic and central effects of exercise. This review will focus on factors relevant to energy metabolism in muscle, such as the 5' adenosine monophosphate-activated protein kinase (AMPK) - sirtuin (SIRT1) - Peroxisome proliferator-activated receptor <i>γ</i> coactivator-1<i>α</i> (PGC-1<i>α</i>) pathway, and the molecules affecting it. In particular, putative exercise-mimetics such as AICAR, metformin, and GW501516 will be discussed. Moreover, plant-derived polyphenols such as resveratrol and (-)epicatechin, with exercise-like effects on the body and brain will be evaluated.</p>","PeriodicalId":72451,"journal":{"name":"Brain plasticity (Amsterdam, Netherlands)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/BPL-160043","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36102056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Timothy B Weng, Gary L Pierce, Warren G Darling, Derik Falk, Vincent A Magnotta, Michelle W Voss
Although there is promising evidence that regular physical activity could counteract age-related decline in cognitive and brain function, the mechanisms for this neuroprotection remain unclear. The acute effects of exercise can provide insight into the mechanisms by which the brain adapts to habitual exercise by reflecting transient modulations of systems that would subsequently accumulate long-term adaptations through repeated training sessions. However, methodological limitations have hindered the mechanistic insight gained from previous studies examining acute exercise effects on the human brain. In the current study, we tested the plasticity of functional brain networks in response to a single stimulus of aerobic exercise using resting-state functional connectivity analyses. In a sample of healthy younger (N = 12; age = 23.2 years; 6 females) and older adults (N = 13; age = 66.3 years; 6 females), we found that 30 minutes of moderate-intensity aerobic cycling selectively increased synchrony among brain regions associated with affect and reward processing, learning and memory, and in regions important for attention and executive control. Importantly, these changes did not occur when the same participants completed a passive, motor-driven control condition. Our results suggest that these transient increases in synchrony serve as a possible avenue for systematically investigating the effects of various exercise parameters on specific brain systems, which may accelerate mechanistic discoveries about the benefits of exercise on brain and cognitive function.
{"title":"The Acute Effects of Aerobic Exercise on the Functional Connectivity of Human Brain Networks.","authors":"Timothy B Weng, Gary L Pierce, Warren G Darling, Derik Falk, Vincent A Magnotta, Michelle W Voss","doi":"10.3233/BPL-160039","DOIUrl":"10.3233/BPL-160039","url":null,"abstract":"<p><p>Although there is promising evidence that regular physical activity could counteract age-related decline in cognitive and brain function, the mechanisms for this neuroprotection remain unclear. The acute effects of exercise can provide insight into the mechanisms by which the brain adapts to habitual exercise by reflecting transient modulations of systems that would subsequently accumulate long-term adaptations through repeated training sessions. However, methodological limitations have hindered the mechanistic insight gained from previous studies examining acute exercise effects on the human brain. In the current study, we tested the plasticity of functional brain networks in response to a single stimulus of aerobic exercise using resting-state functional connectivity analyses. In a sample of healthy younger (<i>N</i> = 12; age = 23.2 years; 6 females) and older adults (<i>N</i> = 13; age = 66.3 years; 6 females), we found that 30 minutes of moderate-intensity aerobic cycling selectively increased synchrony among brain regions associated with affect and reward processing, learning and memory, and in regions important for attention and executive control. Importantly, these changes did not occur when the same participants completed a passive, motor-driven control condition. Our results suggest that these transient increases in synchrony serve as a possible avenue for systematically investigating the effects of various exercise parameters on specific brain systems, which may accelerate mechanistic discoveries about the benefits of exercise on brain and cognitive function.</p>","PeriodicalId":72451,"journal":{"name":"Brain plasticity (Amsterdam, Netherlands)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/BPL-160039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36102059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The pioneer work of Paul Broca (1824-1880) was the first demonstration that brain is functionally not homogeneous, but on the contrary constituted by the assembly of different areas each responsible for specific function. Investigating aphasic patients Broca described a small area in the left frontal lobe, which he described as responsible for articulate language [1, 2]. This region is now known as Broca’s area. Since then the localizationism theory has extended and in association to the long-life concept that only neurons were true functional cells, it has generally been assumed that each brain function is driven by some groups or subpopulation of neurons. As a consequence, any neurological dysfunction had to be attributed to the lesion of a subgroup of neuronal cell. One of the most puzzling situation had been reached by Gerstmann’s syndrome, a condition where a small lesion localized in the dominant inferior parietal lobe results in the association of four apparently completely unrelated symptoms: dysgraphia/agraphia dyscalculia/acalculia, finger agnosia, and left-right disorientation. First described in 1924 by Joseph Gerstmann [3, 4] this syndrome has stirred a controversy for over 80 years among neurologists questioning which population of cortical neurons localized in the angular and supramarginal gyrus could be responsible for such a diversity of cognitive functions. It is only very recently with the development of
{"title":"Live-Imaging of Myelin in Animal Models and in Human.","authors":"Bernard Zalc","doi":"10.3233/BPL-169001","DOIUrl":"https://doi.org/10.3233/BPL-169001","url":null,"abstract":"The pioneer work of Paul Broca (1824-1880) was the first demonstration that brain is functionally not homogeneous, but on the contrary constituted by the assembly of different areas each responsible for specific function. Investigating aphasic patients Broca described a small area in the left frontal lobe, which he described as responsible for articulate language [1, 2]. This region is now known as Broca’s area. Since then the localizationism theory has extended and in association to the long-life concept that only neurons were true functional cells, it has generally been assumed that each brain function is driven by some groups or subpopulation of neurons. As a consequence, any neurological dysfunction had to be attributed to the lesion of a subgroup of neuronal cell. One of the most puzzling situation had been reached by Gerstmann’s syndrome, a condition where a small lesion localized in the dominant inferior parietal lobe results in the association of four apparently completely unrelated symptoms: dysgraphia/agraphia dyscalculia/acalculia, finger agnosia, and left-right disorientation. First described in 1924 by Joseph Gerstmann [3, 4] this syndrome has stirred a controversy for over 80 years among neurologists questioning which population of cortical neurons localized in the angular and supramarginal gyrus could be responsible for such a diversity of cognitive functions. It is only very recently with the development of","PeriodicalId":72451,"journal":{"name":"Brain plasticity (Amsterdam, Netherlands)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/BPL-169001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36102595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Already during the last trimester of gestation, functional responses are recorded in foetuses and preterm newborns, attesting an already complex cerebral architecture. Then throughout childhood, anatomical connections are further refined but at different rates and over asynchronous periods across functional networks. Concurrently, infants gradually achieve new psychomotor and cognitive skills. Only the recent use of non-invasive techniques such as magnetic resonance imaging (MRI) and magneto- and electroencephalography (M/EEG) has opened the possibility to understand the relationships between brain maturation and skills development in vivo. In this review, we describe how these techniques have been applied to study the white matter maturation. At the structural level, the early architecture and myelination of bundles have been assessed with diffusion and relaxometry MRI, recently integrated in multi-compartment models and multi-parametric approaches. Nevertheless, technical limitations prevent us to map major developmental mechanisms such as fibers growth and pruning, and the progressive maturation at the bundle scale in case of mixing trajectories. At the functional level, M/EEG have been used to record different visual, somatosensory and auditory evoked responses. Because the conduction velocity of neural impulses increases with the myelination of connections, major changes in the components latency are observed throughout development. But so far, only a few studies have related structural and functional markers of white matter myelination. Such multi-modal approaches will be a major challenge in future research, not only to understand normal development, but also to characterize early mechanisms of pathologies and the influence of fetal and perinatal interventions on later outcome.
{"title":"MRI and M/EEG studies of the White Matter Development in Human Fetuses and Infants: Review and Opinion.","authors":"Jessica Dubois, Parvaneh Adibpour, Cyril Poupon, Lucie Hertz-Pannier, Ghislaine Dehaene-Lambertz","doi":"10.3233/BPL-160031","DOIUrl":"https://doi.org/10.3233/BPL-160031","url":null,"abstract":"<p><p>Already during the last trimester of gestation, functional responses are recorded in foetuses and preterm newborns, attesting an already complex cerebral architecture. Then throughout childhood, anatomical connections are further refined but at different rates and over asynchronous periods across functional networks. Concurrently, infants gradually achieve new psychomotor and cognitive skills. Only the recent use of non-invasive techniques such as magnetic resonance imaging (MRI) and magneto- and electroencephalography (M/EEG) has opened the possibility to understand the relationships between brain maturation and skills development <i>in vivo</i>. In this review, we describe how these techniques have been applied to study the white matter maturation. At the structural level, the early architecture and myelination of bundles have been assessed with diffusion and relaxometry MRI, recently integrated in multi-compartment models and multi-parametric approaches. Nevertheless, technical limitations prevent us to map major developmental mechanisms such as fibers growth and pruning, and the progressive maturation at the bundle scale in case of mixing trajectories. At the functional level, M/EEG have been used to record different visual, somatosensory and auditory evoked responses. Because the conduction velocity of neural impulses increases with the myelination of connections, major changes in the components latency are observed throughout development. But so far, only a few studies have related structural and functional markers of white matter myelination. Such multi-modal approaches will be a major challenge in future research, not only to understand normal development, but also to characterize early mechanisms of pathologies and the influence of fetal and perinatal interventions on later outcome.</p>","PeriodicalId":72451,"journal":{"name":"Brain plasticity (Amsterdam, Netherlands)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/BPL-160031","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36102053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Geneviève Rougon, Sophie Brasselet, Franck Debarbieux
Purpose of review: Highly coordinated cellular interactions occur in the healthy or pathologic adult rodent central nervous system (CNS). Until recently, technical challenges have restricted the analysis of these events to largely static modes of study such as immuno-fluorescence and electron microscopy on fixed tissues. The development of intravital imaging with subcellular resolution is required to probe the dynamics of these events in their natural context, the living brain. Recent findings: This review focuses on the recently developed live non-linear optical imaging modalities, the core principles involved, the identified technical challenges that limit their use and the scope of their applications. We highlight some practical applications for these modalities with a specific attention given to Experimental Autoimmune Encephalomyelitis (EAE), a rodent model of a chronic inflammatory disease of the CNS characterized by the formation of disseminated demyelinating lesions accompanied by axonal degeneration. Summary: We conclude that label-free nonlinear optical imaging combined to two photon imaging will continue to contribute richly to comprehend brain function and pathogenesis and to develop effective therapeutic strategies.
{"title":"Advances in Intravital Non-Linear Optical Imaging of the Central Nervous System in Rodents.","authors":"Geneviève Rougon, Sophie Brasselet, Franck Debarbieux","doi":"10.3233/BPL-160028","DOIUrl":"10.3233/BPL-160028","url":null,"abstract":"<p><p><b>Purpose of review:</b> Highly coordinated cellular interactions occur in the healthy or pathologic adult rodent central nervous system (CNS). Until recently, technical challenges have restricted the analysis of these events to largely static modes of study such as immuno-fluorescence and electron microscopy on fixed tissues. The development of intravital imaging with subcellular resolution is required to probe the dynamics of these events in their natural context, the living brain. <b>Recent findings:</b> This review focuses on the recently developed live non-linear optical imaging modalities, the core principles involved, the identified technical challenges that limit their use and the scope of their applications. We highlight some practical applications for these modalities with a specific attention given to Experimental Autoimmune Encephalomyelitis (EAE), a rodent model of a chronic inflammatory disease of the CNS characterized by the formation of disseminated demyelinating lesions accompanied by axonal degeneration. <b>Summary:</b> We conclude that label-free nonlinear optical imaging combined to two photon imaging will continue to contribute richly to comprehend brain function and pathogenesis and to develop effective therapeutic strategies.</p>","PeriodicalId":72451,"journal":{"name":"Brain plasticity (Amsterdam, Netherlands)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1d/ac/bpl-2-bpl160028.PMC5928564.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36102597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Positron Emission Tomography (PET), an imaging technique based on the injection of radiotracers directed against specific biological targets within brain tissues, within brain tissues, is a specific and sensitive technique which offers the unique opportunity to quantify myelin dynamics in the central nervous system. Several stilbene and benzothiazole derivatives have been repurposed to image myelin by PET. In demyelinating and dysmyelinating models, selected radiotracers were shown to reliably quantify demyelination and remyelination, allowing a translational approach in humans. A pilot study in subjects with active relapsing MS using PET and the most available benzothiazole derivative, [11C]PIB, supported the hypothesis that this technique is able to quantify myelin content in multiple sclerosis (MS) lesions and to capture dynamic demyelination and remyelination over time. This study highlighted for the first time in vivo the prognostic value of individual profiles of remyelination on the disease course. In future, the clinical application of myelin PET will be pushed forward thanks to the availability of novel fluorinated tracers for myelin, together with the setting up of non invasive quantification procedures and the use of powerful PET-MR systems. This will enable to address in vivo critical unanswered questions about the pathogenesis of remyelination, and to measure the efficacy of emerging promyelinating drugs in early-phase therapeutic trials.
{"title":"Imaging Central Nervous System Demyelination and Remyelination by Positron-Emission Tomography.","authors":"Benedetta Bodini, Bruno Stankoff","doi":"10.3233/BPL-160042","DOIUrl":"https://doi.org/10.3233/BPL-160042","url":null,"abstract":"<p><p>Positron Emission Tomography (PET), an imaging technique based on the injection of radiotracers directed against specific biological targets within brain tissues, within brain tissues, is a specific and sensitive technique which offers the unique opportunity to quantify myelin dynamics in the central nervous system. Several stilbene and benzothiazole derivatives have been repurposed to image myelin by PET. In demyelinating and dysmyelinating models, selected radiotracers were shown to reliably quantify demyelination and remyelination, allowing a translational approach in humans. A pilot study in subjects with active relapsing MS using PET and the most available benzothiazole derivative, [<sup>11</sup>C]PIB, supported the hypothesis that this technique is able to quantify myelin content in multiple sclerosis (MS) lesions and to capture dynamic demyelination and remyelination over time. This study highlighted for the first <i>time in vivo</i> the prognostic value of individual profiles of remyelination on the disease course. In future, the clinical application of myelin PET will be pushed forward thanks to the availability of novel fluorinated tracers for myelin, together with the setting up of non invasive quantification procedures and the use of powerful PET-MR systems. This will enable to address <i>in vivo</i> critical unanswered questions about the pathogenesis of remyelination, and to measure the efficacy of emerging promyelinating drugs in early-phase therapeutic trials.</p>","PeriodicalId":72451,"journal":{"name":"Brain plasticity (Amsterdam, Netherlands)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/BPL-160042","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36102599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
For a long time, although the functional anatomy of human cortex has extensively been studied, subcortical white matter tracts have received little consideration. Recent advances in tractography have opened the door to a non-invasive investigation of the subcortical fibers in vivo. However, this method cannot study directly the function of the bundles. Interestingly, for the first time in the history of cognitive neurosciences, direct axonal electrostimulation (DES) mapping of the neural pathways offers the unique opportunity to investigate the function of the connectomal anatomy. Indeed, this technique is able to perform real-time anatomo-functional correlations in awake patients who undergo brain surgery, especially at the level of the subcortical fibers. Here, the aim is to review original data issued from DES of myelinated tracts in adults, with regard to the functional connectivity mediating the sensorimotor, visuo-spatial, language, cognitive and emotional functions, as well as the interactions between these different sub-networks, leading ultimately to explore consciousness. Therefore, axonal stimulation is a valuable tool in the field of connectomics, that is, the map of neural connections, in order to switch from the traditional localizationist view of brain processing to a networking model in which cerebral functions are underpinned by the dynamic interactions of large-scale distributed and parallel sub-circuits. Such connectomal account should integrate the anatomic constraint represented by the subcortical fascicles. Indeed, post-lesional neuroplasticity is possible only on the condition that the white matter fibers are preserved, to allow communication and temporal synchronization among delocalized inter-connected networks.
长期以来,虽然对人类大脑皮层的功能解剖进行了广泛的研究,但对皮层下白质束的研究却很少。最近,束成像技术的进步为在体内对皮层下纤维进行非侵入性研究打开了大门。然而,这种方法无法直接研究纤维束的功能。有趣的是,在认知神经科学的历史上,直接轴突电刺激(DES)绘制神经通路图首次为研究连接解剖结构的功能提供了独特的机会。事实上,这项技术能够对接受脑部手术的清醒患者进行实时解剖功能关联分析,尤其是在皮层下纤维水平。本文旨在回顾成人髓鞘束 DES 所获得的原始数据,这些数据涉及介导感觉运动、视觉空间、语言、认知和情感功能的功能连接,以及这些不同子网络之间的相互作用,最终导致对意识的探索。因此,轴突刺激是连接组学(即神经连接图谱)领域的一个重要工具,可将大脑处理从传统的局部化观点转变为网络模型,即大脑功能由大规模分布式并行子回路的动态互动支撑。这种联结模式应结合皮层下束带所代表的解剖学约束。事实上,只有在保留白质纤维的条件下,病变后的神经可塑性才有可能实现,从而使分散的相互连接的网络之间实现通信和时间同步。
{"title":"Stimulation Mapping of Myelinated Tracts in Awake Patients.","authors":"Hugues Duffau","doi":"10.3233/BPL-160027","DOIUrl":"10.3233/BPL-160027","url":null,"abstract":"<p><p>For a long time, although the functional anatomy of human cortex has extensively been studied, subcortical white matter tracts have received little consideration. Recent advances in tractography have opened the door to a non-invasive investigation of the subcortical fibers <i>in vivo</i>. However, this method cannot study directly the function of the bundles. Interestingly, for the first time in the history of cognitive neurosciences, direct axonal electrostimulation (DES) mapping of the neural pathways offers the unique opportunity to investigate the function of the connectomal anatomy. Indeed, this technique is able to perform real-time anatomo-functional correlations in awake patients who undergo brain surgery, especially at the level of the subcortical fibers. Here, the aim is to review original data issued from DES of myelinated tracts in adults, with regard to the functional connectivity mediating the sensorimotor, visuo-spatial, language, cognitive and emotional functions, as well as the interactions between these different sub-networks, leading ultimately to explore consciousness. Therefore, axonal stimulation is a valuable tool in the field of connectomics, that is, the map of neural connections, in order to switch from the traditional localizationist view of brain processing to a networking model in which cerebral functions are underpinned by the dynamic interactions of large-scale distributed and parallel sub-circuits. Such connectomal account should integrate the anatomic constraint represented by the subcortical fascicles. Indeed, post-lesional neuroplasticity is possible only on the condition that the white matter fibers are preserved, to allow communication and temporal synchronization among delocalized inter-connected networks.</p>","PeriodicalId":72451,"journal":{"name":"Brain plasticity (Amsterdam, Netherlands)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fb/12/bpl-2-bpl160027.PMC5928548.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36102054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Myelin is critical for healthy brain function. An accurate in vivo measure of myelin content has important implications for understanding brain plasticity and neurodegenerative diseases. Myelin water imaging is a magnetic resonance imaging method which can be used to visualize myelination in the brain and spinal cord in vivo. This review presents an overview of myelin water imaging data acquisition and analysis, post-mortem validation work, findings in both animal and human studies and a brief discussion about other MR techniques purported to provide in vivo myelin content. Multi-echo T2 relaxation approaches continue to undergo development and whole-brain imaging time now takes less than 10 minutes; the standard analysis method for this type of data acquisition is a non-negative least squares approach. Alternate methods including the multi-flip angle gradient echo mcDESPOT are also being used for myelin water imaging. Histological validation studies in animal and human brain and spinal cord tissue demonstrate high specificity of myelin water imaging for myelin. Potential confounding factors for in vivo myelin water fraction measurement include the presence of myelin debris and magnetization exchange processes. Myelin water imaging has successfully been used to study animal models of injury, applied in healthy human controls and can be used to assess damage and injury in conditions such as multiple sclerosis, neuromyelitis optica, schizophrenia, phenylketonuria, neurofibromatosis, niemann pick's disease, stroke and concussion. Other quantitative magnetic resonance approaches that are sensitive to, but not specific for, myelin exist including magnetization transfer, diffusion tensor imaging and T1 weighted imaging.
{"title":"Magnetic Resonance of Myelin Water: An <i>in vivo</i> Marker for Myelin.","authors":"Alex L MacKay, Cornelia Laule","doi":"10.3233/BPL-160033","DOIUrl":"https://doi.org/10.3233/BPL-160033","url":null,"abstract":"<p><p>Myelin is critical for healthy brain function. An accurate <i>in vivo</i> measure of myelin content has important implications for understanding brain plasticity and neurodegenerative diseases. Myelin water imaging is a magnetic resonance imaging method which can be used to visualize myelination in the brain and spinal cord <i>in vivo</i>. This review presents an overview of myelin water imaging data acquisition and analysis, post-mortem validation work, findings in both animal and human studies and a brief discussion about other MR techniques purported to provide <i>in vivo</i> myelin content. Multi-echo T<sub>2</sub> relaxation approaches continue to undergo development and whole-brain imaging time now takes less than 10 minutes; the standard analysis method for this type of data acquisition is a non-negative least squares approach. Alternate methods including the multi-flip angle gradient echo mcDESPOT are also being used for myelin water imaging. Histological validation studies in animal and human brain and spinal cord tissue demonstrate high specificity of myelin water imaging for myelin. Potential confounding factors for <i>in vivo</i> myelin water fraction measurement include the presence of myelin debris and magnetization exchange processes. Myelin water imaging has successfully been used to study animal models of injury, applied in healthy human controls and can be used to assess damage and injury in conditions such as multiple sclerosis, neuromyelitis optica, schizophrenia, phenylketonuria, neurofibromatosis, niemann pick's disease, stroke and concussion. Other quantitative magnetic resonance approaches that are sensitive to, but not specific for, myelin exist including magnetization transfer, diffusion tensor imaging and T<sub>1</sub> weighted imaging.</p>","PeriodicalId":72451,"journal":{"name":"Brain plasticity (Amsterdam, Netherlands)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/BPL-160033","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36102600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Myelination by oligodendrocytes in the central nervous system (CNS) and Schwann cells in the peripheral nervous system is essential for nervous system function and health. Despite its importance, we have a relatively poor understanding of the molecular and cellular mechanisms that regulate myelination in the living animal, particularly in the CNS. This is partly due to the fact that myelination commences around birth in mammals, by which time the CNS is complex and largely inaccessible, and thus very difficult to image live in its intact form. As a consequence, in recent years much effort has been invested in the use of smaller, simpler, transparent model organisms to investigate mechanisms of myelination in vivo. Although the majority of such studies have employed zebrafish, the Xenopus tadpole also represents an important complementary system with advantages for investigating myelin biology in vivo. Here we review how the natural features of zebrafish embryos and larvae and Xenopus tadpoles make them ideal systems for experimentally interrogating myelination by live imaging. We outline common transgenic technologies used to generate zebrafish and Xenopus that express fluorescent reporters, which can be used to image myelination. We also provide an extensive overview of the imaging modalities most commonly employed to date to image the nervous system in these transparent systems, and also emerging technologies that we anticipate will become widely used in studies of zebrafish and Xenopus myelination in the near future.
{"title":"Imaging Myelination <i>In Vivo</i> Using Transparent Animal Models.","authors":"Jenea M Bin, David A Lyons","doi":"10.3233/BPL-160029","DOIUrl":"10.3233/BPL-160029","url":null,"abstract":"<p><p>Myelination by oligodendrocytes in the central nervous system (CNS) and Schwann cells in the peripheral nervous system is essential for nervous system function and health. Despite its importance, we have a relatively poor understanding of the molecular and cellular mechanisms that regulate myelination in the living animal, particularly in the CNS. This is partly due to the fact that myelination commences around birth in mammals, by which time the CNS is complex and largely inaccessible, and thus very difficult to image live in its intact form. As a consequence, in recent years much effort has been invested in the use of smaller, simpler, transparent model organisms to investigate mechanisms of myelination <i>in vivo</i>. Although the majority of such studies have employed zebrafish, the <i>Xenopus</i> tadpole also represents an important complementary system with advantages for investigating myelin biology <i>in vivo</i>. Here we review how the natural features of zebrafish embryos and larvae and <i>Xenopus</i> tadpoles make them ideal systems for experimentally interrogating myelination by live imaging. We outline common transgenic technologies used to generate zebrafish and <i>Xenopus</i> that express fluorescent reporters, which can be used to image myelination. We also provide an extensive overview of the imaging modalities most commonly employed to date to image the nervous system in these transparent systems, and also emerging technologies that we anticipate will become widely used in studies of zebrafish and <i>Xenopus</i> myelination in the near future.</p>","PeriodicalId":72451,"journal":{"name":"Brain plasticity (Amsterdam, Netherlands)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/75/fe/bpl-2-bpl160029.PMC5928531.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36102598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}