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Neural Plasticity And Disorders Of The Nervous System Pdf

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One major goal in Neuroscience is the development of strategies promoting neural plasticity in the adult central nervous system, when functional recovery from brain disease and injury is limited. New evidence has underscored a pivotal role for cortical inhibitory circuitries in regulating plasticity both during development and in adulthood. This paper summarizes recent findings showing that the inhibition-excitation balance controls adult brain plasticity and is at the core of the pathogenesis of neurodevelopmental disorders like autism, Down syndrome, and Rett syndrome.

Accelerations in the x and y dimensions demonstrating use-dependent plasticity. Data are from 20 healthy subjects. Vectors represent both mean angles and movement accelerations. Use-dependent plasticity is accomplished in several steps. In pretraining, the spontaneous direction of transcranial magnetic stimulation TMS —induced movement is measured.


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.

The structural-pathology paradigm helps to comprehend and guide treatment effectively in acute MSD. There are however many unanswered questions and discrepant findings with chronic MSD where the structural-pathology paradigm fails as a working model for comprehension, research and in treatment. These include allusive questions such as why diagnostic findings correlate poorly with pain and dysfunction, the presence of bilateral findings with unilateral injuries, why a large proportion of persons with damage to musculoskeletal structures are asymptomatic, why some persons heal and others develop chronic MSD, and persisting sensory motor abnormalities [ 2 - 6 ].

In an attempt to better understand the clinical and experimental manifestations of these disorders researchers have expanded their scope of inquiry to include neurophysiological processes and plasticity within the Central Nervous System CNS associated with MSD. These changes are believed to be reflective of adaptive neurophysiological processes occurring with MSD that are initially beneficial and aid in the healing process by protecting the injured structures from further insult.

In a chronic state, the structural pathology paradigm dictates that that these neuroplastic changes associated with chronic MSD are secondary to the injury and result from ongoing altered sensory transmission arising from the area of the musculoskeletal injury. Clinical and experiment findings however challenge this belief and demonstrate that neurophysiological adaptations may persist and be implicated in the development and maintenance of chronic signs and symptoms, possibly in lieu of healing to the peripheral musculoskeletal structures or co-existing with peripheral mechanisms [ 1 , 11 ].

According to this hypothesis, associative learning resulting from the initial trauma and subsequent events that reinforces the concurrent pairing between movement and pain results in an aversive association that is reflected and maintained by plastic changes in the meso-limbic and prefrontal areas [ 15 ]. These neuroplastic changes explain many of the experimental and clinical findings present in subjects with chronic MSD.

These changes result in sensory amplification [ 16 ], changes in sensory and motor representations [ 17 - 19 ] resulting in perceptual changes in body image [ 20 , 21 ], changes in motor control [ 22 ], bilateral experimental findings [ 23 - 25 ], the persistence and amplification of pain [ 16 , 26 ], and why some individuals transit from acute to chronic disorders [ 27 , 28 ].

Further evidence arguing to the importance of these neurophysiological adaptations stem from recent studies targeting neuronal processes appear to restore function and decrease pain [ 14 , 29 , 30 ].

These findings are highly relevant for the design and implementation of rehabilitative interventions for MSD which when guided by the structural-pathology paradigm have limited success in the treatment of many of these chronic conditions [ 31 ].

If neuroplastic changes in the CNS are not simply an epiphenomenon but are part and parcel to the pathophysiological process in chronic MSD, interventions that target these underlying pathophysiological mechanisms have the greatest chance of success [ 32 ]. The structural pathology paradigm is guided by the inherent belief that pain and other neurophysiological changes are secondary to local structural insult to musculoskeletal structures.

Both in animal and human studies, it is apparent that local and systemic inflammatory responses, cellular and vascular proliferative changes as well as degeneration and fibrosis are all hallmarks of chronic and overuse MSD [ 34 , 36 - 41 ]. Injury to musculoskeletal structures, inflammatory mediators, and subsequent fibrosis change the mechanics of muscles and connective tissues affecting their physical properties and these in turn impact sensory receptor activity and transmission [ 11 , 34 , 42 - 46 ].

Under the structural-pathology paradigm neurophysiological consequences, with the exception of damage to the nerve s , is secondary and should disappear when normal tissue properties are restored and receptor activity, sensory transmission, and perception should renormalize to reflect the state of the healed structure s. Within this paradigm pain is simply a symptom and reflects the degree of damage to the musculoskeletal structure and associated biological responses locally in the area of injury.

This viewpoint is supported by the findings that demonstrates the reversal of some, but not all Central Nervous System CNS changes when anatomical insult to musculoskeletal structures and pain disappears [ 47 , 48 ]. This paradigm however fails to explain many of the experimental findings with chronic MSD. For example, on a population level anatomical insult to musculoskeletal structures correlates poorly with diagnostic findings and these across a wide range of musculoskeletal disorders [ 2 - 6 ].

Therefore structural damage to musculoskeletal structures alone cannot always fully explain the presence of signs and symptoms in chronic MSD. Neuroplasticity refers to changes in neuronal properties, structure and organization and is the manner in which the nervous system encodes new experiences. Neuroplastic changes have been demonstrated in response to experience and behaviour [ 53 - 56 ], motor learning [ 57 - 62 ], pain [ 17 , 63 - 65 ], injury [ 66 , 67 ], sensory stimuli [ 68 - 71 ], and cognitive processes [ 53 , 56 , 72 , 73 ].

Changes can be transient, reflecting the adaptability of the sensorimotor system to respond to internal and environmental demands and can occur over short training periods [ 74 , 75 ].

Neuroplastic changes in sensory-motor areas are stimulus driven and result in lasting neuroplastic changes when the internal and external pressures are repetitive, salient, involve learning and require sustained attention [ 7 , 53 , 54 , 76 - 78 ]. Neuroplastic changes have been observed in different areas of the CNS including the spinal cord, subcortical and cortical areas.

These studies include findings of changes in perception threshold to noxious and innocuous stimuli, but also other sensory alterations including stimuli being processed more slowly, incorrect localization, and decreased accuracy in recognition of tactile stimulation [ 43 , 79 , 81 - 85 , 87 - 92 ]. These changes have been demonstrated bilaterally and in sites remote to the initial injury [ 81 , 83 , 93 ]. Proprioceptive deficits include increased errors in repositioning [ 94 - 96 ], decreased position sense and ability to detect joint motion [ 97 , 98 ], difficulty to adopt postures seen on a photograph [ 87 , 89 ] across a number of MSD.

Although not all studies involving subjects with chronic MSD demonstrate altered sensory transmission [ 99 ] many studies with chronic MSD demonstrate augmented nociceptive transmission involving responsiveness to normally sub threshold nociceptive stimuli that results in hyperlagesia, an increase in nociceptive transmission and pain perception, indicative of an altered stimulus—response relationship to nociceptive stimuli, a process called Central Sensitization [ 16 , 26 , 83 - 85 , - ].

This is a normal, adaptive and reversible process that is biologically advantageous to protect the injured structure from further insult and is a consistent notion within the structural-pathology paradigm [ 26 ]. Neurophysiological changes also result in the amplification of noxious and innocuous stimuli within the dorsal horn of the spinal cord that persist in chronic pain states. These changes are reflective of processes similar to experience dependent plasticity and result from segmental, spinal and supraspinal processes that modulate membrane excitability and affect inhibitory and facilitatory processes within the spinal cord see [ 16 ].

Some dorsal horn nociceptive neurons develop increased receptor field size wide-dynamic range neurons responding to nociceptive and cutaneous stimuli that results in secondary hyperalgesia and allodynia spread and perception of pain with innocuous stimulation [ 16 ]. The supraspinal influences on dorsal horn nociceptive transmission include descending pain modulatory systems including the Periaqueductal grey PAG -Rostral Ventromedial RVM pathway.

Under normal circumstances these systems inhibit the transmission of nociceptive stimuli in the dorsal horn of the spinal cord [ ]. There exists convincing evidence in animal models that these descending modulatory systems are disrupted in chronic pain subjects shifting from a state of inhibition to a mal-adaptive state of facilitation amplifying the transmission of nociceptive stimuli, contributing to the process of central sensitization, and perpetuating the augmented transmission of neuropathic stimuli [ 16 , 45 , ].

For example, an increase in activity of cells that project to the dorsal horn of the spinal cord from the RVM that facilitate the transmission of noxious stimuli is present only in animals with neuropathic pain behaviours [ ]. In CLBP patients there is a decrease in PAG cerebral blood flow not seen in healthy control subjects suggestive of decreased neuronal activity [ ]. In humans there is evidence that the a test noxious stimulus, under normal circumstances, is inhibited by a preceding noxious conditioning stimulus, a process called Conditioned Pain Modulation [ ], and is disturbed in subjects in some MSD and chronic pain states [ , ].

Collectively the results from these studies demonstrate that the PAG-RVM pathway not only facilitates nociceptive transmission in the dorsal horn of the spinal cord but actually perpetuates the transmission of pain.

Neuroplastic changes amplifying sensory transmission have functional implications. Subjects demonstrating central sensitization, hypersensitivity and allodynia have a poorer prognosis to treatment including surgical interventions for varied MSD [ 12 , , , ]. Furthermore, studies in both animals and humans demonstrate that altered sensory transmission may result in changes in neuronal properties and organization within different subcortical and cortical areas including the thalamus, primary somatosensory cortex S1 and the primary motor cortex M1 implicated in sensory transmission, perception and motor control [ , ].

Studies of cortical properties and organisation within the sensorimotor areas have been performed with subjects with PFPS [ ], anterior cruciate ligament ACL deficiency and reconstruction [ 33 , - ], CLBP [ 17 - 19 , - ], cervical pain and whiplash injury [ 91 , ], rotator cuff tears [ , ], dystonia [ - ] and CTS [ - ]. These studies suggest that neuronal properties, organization, and morphometric changes are present in subjects with chronic MSD.

For example, subjects with CLBP demonstrate a 2. Studies in subjects with CTS reveal changes along the afferent pathway in the spinal cord, brain stem and S1 [ ], a decrease in grey matter volume [ ] and a loss of spatially segregated representations of digits 2 and digits 3 in the contralateral S1 that correlate with changes in nerve conduction velocity [ , , ]. Somatotopic re-organisation in CTS subjects are specific to the nature of sensory stimuli as the representation of the digits in S1 is decreased with pain and increased with paraesthesia [ ].

In the perspective of the structural-pathology paradigm, these changes in S1 associated with MSD may simply be reflective of altered peripheral sensory transmission reflective of altered afferent peripheral sensory stimuli and transmission occurring as the result of insult to musculoskeletal structures and inflammation. Studies in non-human primates with peripheral de-afferentation and spinal cord injury demonstrate degeneration in the cuneate nucleus of the brainstem, an area that contains axons from the dorsal root ganglion transmitting cutaneous and proprioceptive stimuli, as well as somatotopic reorganization in an area of the thalamus ventral posterior lateral nucleus that transmits sensory afferent stimuli to S1.

The changes in S1 in these studies mirror the changes found in the thalamus suggesting that the changes in sensory afference including noxious, cutaneous, and possibly proprioceptive afferent transmission are implicated in S1 reorganization [ , ]. However, should altered afferent transmission persist, potentiated by functional changes in the brain stem and the spinal cord, neurophysiological changes appear to result in behavioural and functional implications that are not simply a reflection of altered sensory afference.

There is growing evidence that pain associated with MSD such as osteoarthritis and CLBP may be, at least in part, the result of the plasticity of the sensory representation of the body and perceptual disturbances [ - ].

These changes include the sensation of abnormal size, shape, swelling, and position [ 30 ]. Perceptual changes also have functional implications. Incongruence and manipulation between sensory and motor input has been shown to cause sensory disturbances, and aggravate symptoms and pain [ ].

Modulation of the shape and size of a limb can impact tactile acuity and pain [ ]. Visual distortion of the hands in subjects with osteoarthritis helps to decrease pain [ ]. Interventions targeting changes in somatotopic reorganization through the use of sensory discriminative training and visual distortion can renormalize the S1 representation and decrease pain [ 30 , , - ].

The modulation of the size of the limb can alter subjective feelings of pain and motor imagery can cause an increase in pain and swelling that cannot be attributed to increased peripheral sensory afference arising from nociceptors or peripheral neural injury [ , ].

The persistence of abnormal motor imagery in recurrent low back subjects is also believed to be reflective of ongoing disruption of cortical maps even in the absence of pain [ ]. These findings support the belief that structural injury to musculoskeletal structures are not the only driver of pain and dysfunction, CNS changes play an active role in the pathophysiology of chronic pain conditions, and interventions that target these CNS changes may decrease pain, improve function, and even affect mechanisms involved in the local biological response to injured structures such as swelling.

Studies that investigate changes in the properties, function and organisation within the primary motor cortex M1 of subjects with different MSD have been performed, of which the majority utilise Transcranial Magnetic Stimulation TMS. TMS produces a high intensity electrical pulse resulting in a magnetic field perpendicular to the stimulating coil. The magnetic pulse traverses the skull and when applied over the motor cortex with sufficient intensity, can depolarize corticospinal neurons directly or indirectly.

This stimulation results in the depolarization of different motoneuron pools within the spinal cord and an electromyographic response, the Motor Evoked Potential MEP can be recorded.

Utilising different parameters of stimulation and experimental protocols, TMS allows for the appreciation of corticospinal excitability, inhibitory and facilitatory processes, and somatotopic organization of corticospinal neurons.

Collectively these studies demonstrate changes in corticospinal excitability that correlate with pain and disability scores. Changes in motor behaviour that are present in subjects with CMSD appear to be largely mediated by changes in the cortical areas including M1.

Inhibition of corticospinal output is increased in experimentally induced muscle pain resulting in decreased motor responses to TMS at rest [ ] and increased corticospinal output during forceful muscle contractions [ , ]. In a series of experiments Tsao and his colleagues investigated the properties and organization of the representation of muscles in the lumbar spine within M1 in subjects with CLBP.

They demonstrated that the area of corticospinal recruitment of muscles of the lumbar spine in M1 is altered in CLBP subjects [ 18 ]. These changes correlate with changes in motor recruitment [ 18 , 19 ]. Motor skill learning involving exercises to specifically recruit the transverse abdominus muscle, but not a walking exercise, could restore the representation within M1 and EMG activation pattern in CLBP subjects to that seen in healthy controls [ ]. The changes in the representation of the movements elicited by the trunk muscles in M1 are associated with the impaired activation of these muscles and may underpin changes in motor activation, specifically the inability to selectively recruit these muscles.

This, in turn is consistent with the increased activation of superficial muscles in this population when performing movements [ ] and the altered activation of the multifidus that has been demonstrated in patients with recurrent LBP [ , ].

These studies demonstrate that neuronal properties and organisation within M1 are modified in CLBP subjects and that intervention specifically targeting these representational changes improve function and decrease pain. The relationship between the plastic changes in the spinal cord, brain stem and cortical sensori-motor areas are complex.

If these processes remain present for a substantial period of time they may result in lasting neurophysiological adaptations that may become imprinted and can outlive the insult to peripheral musculoskeletal structures [ 14 , 15 ]. It is important to note that a return to before injury sensory transmission and the performance of repetitive strengthening exercises may not be sufficient to return the neuronal properties and organization within the sensorimotor areas to a pre-injury state [ ].

Specific interventions addressing these neuroplastic changes in sensorimotor areas appear to be required. Repetitive unskilled movements do not result in neuroplastic changes in M1 [ 57 , 76 ]. Motor skill training however has proven successful in the treatment of some musculoskeletal conditions, improves task performance and helps promote neuroplastic changes in M1 [ 53 , , - ].

These findings are suggestive that the neuroplastic changes in the sensory-motor areas are implicated in the pathophysiology of some chronic MSD and should impact rehabilitative treatments.

Findings from experimental studies do provide convincing evidence that pain provides an impetus for CNS changes with MSD. Experimentally induced pain impacts neuronal properties and organisation in S1 and M1 [ , ] and subjects with chronic pain associated with unilateral herpes simplex virus have a decreased representation between digits 1—5 in the contralateral S1 [ ].

Although the causal relationship between pain and cortical reorganization has not been definitively established with MSD, the evidence suggests that pain is a driver of cortical re-organization. In other conditions where re-organisation in S1 is present there is a renormalisation with the attenuation of pain [ , ] and some, but not all, of the morphological changes in brain grey matter volume and changes in cortical somatotopy return to those seen in normal healthy subjects when pain is eliminated [ 47 , 48 , , ].

Regulation of CNS Plasticity Through the Extracellular Matrix

Brandon A. Miller, John C. Gensel, Michael S. Plasticity is a defining characteristic of the central nervous system CNS. The ability of the CNS to physically change over the life of the organism, including myelination, neuronal proliferation, and synaptic changes, remains a topic of research in every subdiscipline of neuroscience from molecular to developmental neuroscience. The lay public also seeks a better understanding of neural plasticity. While the CNS has incredible plasticity compared to other organ systems, it also has unique sensitivity to injury.

CNS Plasticity in Injury and Disease

Brain plasticity, also known as neuroplasticity, is a term that refers to the brain's ability to change and adapt as a result of experience. When people say that the brain possesses plasticity, they are not suggesting that the brain is similar to plastic. Neuro refers to neurons , the nerve cells that are the building blocks of the brain and nervous system, and plasticity refers to the brain's malleability.

Neuroplasticity , also known as neural plasticity , or brain plasticity , is the ability of neural networks in the brain to change through growth and reorganization. These changes range from individual neuron pathways making new connections, to systematic adjustments like cortical remapping. Examples of neuroplasticity include circuit and network changes that result from learning a new ability, environmental influences, practice, and psychological stress. Neuroplasticity was once thought by neuroscientists to manifest only during childhood, [7] [8] but research in the latter half of the 20th century showed that many aspects of the brain can be altered or are "plastic" even through adulthood.

Contrary to established dogma, the central nervous system CNS has a capacity for regeneration and is moderately plastic. Traditionally, such changes have been recognized through development, but more recently, this has been documented in adults through learning and memory or during the advent of trauma and disease.

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Информация, которую он выдал. Если Стратмор получил от Следопыта информацию, значит, тот работал. Она оказалась бессмысленной, потому что он ввел задание в неверной последовательности, но ведь Следопыт работал. Но Сьюзан тут же сообразила, что могла быть еще одна причина отключения Следопыта. Внутренние ошибки программы не являлись единственными причинами сбоя, потому что иногда в действие вступали внешние силы - скачки напряжения, попавшие на платы частички пыли, повреждение проводов. Поскольку за техникой Третьего узла следили самым тщательным образом, она даже не рассматривала такую возможность. Сьюзан встала и быстро подошла к громадному книжному шкафу с техническими руководствами, взяла с полки справочник с прошитым проволочной спиралью корешком и принялась его листать.

Я уже говорила, что мы ушли до их прибытия. - Вы хотите сказать - после того как стащили кольцо. - Мы его не украли, - искренне удивилась Росио.  - Человек умирал, и у него было одно желание. Мы просто исполнили его последнюю волю. Беккер смягчился.

Хейл вскипел: - Послушайте меня, старина. Вы отпускаете меня и Сьюзан на вашем лифте, мы уезжаем, и через несколько часов я ее отпускаю. Стратмор понял, что ставки повышаются.

Открыв полку над головой, он вспомнил, что багажа у него. Времени на сборы ему не дали, да какая разница: ему же обещали, что путешествие будет недолгим - туда и обратно. Двигатели снизили обороты, и самолет с залитого солнцем летного поля въехал в пустой ангар напротив главного терминала. Вскоре появился пилот и открыл люк. Беккер быстро допил остатки клюквенного сока, поставил стакан на мокрую столешницу и надел пиджак.

Dysfunctional Neural Plasticity in Patients With Schizophrenia

 - Мне просто нужно узнать, улетела ли. И больше. Женщина сочувственно кивнула.

АНБ является счастливым обладателем алгоритма Цифровой крепости, просто мы не в состоянии его открыть. Сьюзан не могла не восхититься умом Танкадо. Не открыв своего алгоритма, он доказал АНБ, что тот не поддается дешифровке. Стратмор протянул Сьюзан газетную вырезку. Это был перевод рекламного сообщения Никкей симбун, японского аналога Уолл-стрит джорнал, о том, что японский программист Энсей Танкадо открыл математическую формулу, с помощью которой можно создавать не поддающиеся взлому шифры.

Brain Plasticity and Disease: A Matter of Inhibition


Saulorapass 04.06.2021 at 21:09

Neural Plasticity and Disorders of the Nervous System provides comprehensive coverage of the pathophysiology of neurological disorders emphasizing those.

Norris G. 11.06.2021 at 16:19

In biology , the nervous system is a highly complex part of an animal that coordinates its actions and sensory information by transmitting signals to and from different parts of its body.