Motor cortex reorganization across the lifespan

The brain is a highly dynamic structure with the capacity for profound structural and functional change. Such neural plasticity has been well characterized within motor cortex and is believed to represent one of the neural mechanisms for acquiring and modifying motor behaviors. A number of behavioral and neural signals have been identified that modulate motor cortex plasticity throughout the lifespan in both the intact and damaged brain. Specific signals discussed in this review include: motor learning in the intact brain, motor relearning in the damaged brain, cortical stimulation, stage of development and genotype. Clinicians are encouraged to harness these signals in the development and implementation of treatment so as to maximally drive neural plasticity and functional improvements in speech, language and swallowing.Learning outcomes: Readers will be able to: (1) describe a set of behavioral and neural signals that modulate motor cortex plasticity in the intact and damaged brain; (2) describe the influence of stage of development on plasticity and functional outcomes; and (3) identify a known genotype that alters the capacity for motor learning and brain plasticity.     

Experience-dependent neural plasticity in the adult damaged brain

Behavioral experience is at work modifying the structure and function of the brain throughout the lifespan, but it has a particularly dramatic influence after brain injury. This review summarizes recent findings on the role of experience in reorganizing the adult damaged brain, with a focus on findings from rodent stroke models of chronic upper extremity (hand and arm) impairments. A prolonged and widespread process of repair and reorganization of surviving neural circuits is instigated by injury to the adult brain. When experience impacts these same neural circuits, it interacts with degenerative and regenerative cascades to shape neural reorganization and functional outcome. This is evident in the cortical plasticity resulting from compensatory reliance on the "good" forelimb in rats with unilateral sensorimotor cortical infarcts. Behavioral interventions (e.g., rehabilitative training) can drive functionally beneficial neural reorganization in the injured hemisphere. However, experience can have both behaviorally beneficial and detrimental effects. The interactions between experience-dependent and injury-induced neural plasticity are complex, time-dependent, and varied with age and other factors. A better understanding of these interactions is needed to understand how to optimize brain remodeling and functional outcome. LEARNING OUTCOMES: Readers will be able to describe (a) experience effects that are maladaptive for behavioral outcome after brain damage, (b) manipulations of experience that drive functionally beneficial neural plasticity, and (c) reasons why rehabilitative training effects can be expected to vary with age, training duration and timing.     

Principles of experience-dependent neural plasticity: implications for rehabilitation after brain damage.

PURPOSE: This paper reviews 10 principles of experience-dependent neural plasticity and considerations in applying them to the damaged brain. METHOD: Neuroscience research using a variety of models of learning, neurological disease, and trauma are reviewed from the perspective of basic neuroscientists but in a manner intended to be useful for the development of more effective clinical rehabilitation interventions. RESULTS: Neural plasticity is believed to be the basis for both learning in the intact brain and relearning in the damaged brain that occurs through physical rehabilitation. Neuroscience research has made significant advances in understanding experience-dependent neural plasticity, and these findings are beginning to be integrated with research on the degenerative and regenerative effects of brain damage. The qualities and constraints of experience-dependent neural plasticity are likely to be of major relevance to rehabilitation efforts in humans with brain damage. However, some research topics need much more attention in order to enhance the translation of this area of neuroscience to clinical research and practice. CONCLUSION: The growing understanding of the nature of brain plasticity raises optimism that this knowledge can be capitalized upon to improve rehabilitation efforts and to optimize functional outcome.     

Measuring and inducing brain plasticity in chronic aphasia

Brain plasticity associated with anomia recovery in aphasia is poorly understood. Here, I review four recent studies from my lab that focused on brain modulation associated with long-term anomia outcome, its behavioral treatment, and the use of transcranial brain stimulation to enhance anomia treatment success in individuals with chronic aphasia caused by left hemisphere stroke. In a study that included 15 participants with aphasia who were compared to a group of 10 normal control subjects, we found that improved naming ability was associated with increased left hemisphere activity. A separate study (N = 26) revealed similar results in that improved anomia treatment outcome was associated with increased left hemisphere recruitment. Taken together, these two studies suggest that improved naming in chronic aphasia relies on the damaged left hemisphere. Based on these findings, we conducted two studies to appreciate the effect of using low current transcranial electrical stimulation as an adjuvant to behavioral anomia treatment. Both studies yielded positive findings in that anomia treatment outcome was improved when it was coupled with real brain stimulation as compared with a placebo (sham) condition. Overall, these four studies support the notion that the intact cortex in the lesioned left hemisphere supports anomia recovery in aphasia. LEARNING OUTCOMES: Readers will (a) be able to appreciate the possible influence of animal research upon the understanding of brain plasticity induced by aphasia treatment, (b) understand where functional changes associated with anomia treatment occur in the brain, (c) understand the basic principles of transcranial direct current stimulation, and (d) understand how brain stimulation coupled with aphasia treatment may potentially improve treatment outcome.     

Neural bases of recovery after brain injury

Substantial data have accumulated over the past decade indicating that the adult brain is capable of substantial structural and functional reorganization after stroke. While some limited recovery is known to occur spontaneously, especially within the first month post-stroke, there is currently significant optimism that new interventions based on the modulation of neuroplasticity mechanisms will provide greater functional benefits in a larger population of stroke survivors. To place this information in the context of current thinking about brain plasticity, this review outlines the basic theories of why spontaneous recovery occurs, and introduces important principles to explain the effects of post-stroke behavioral experience on neural plasticity. LEARNING OUTCOMES: Readers will be able to: (a) explain the three classic theories to explain spontaneous recovery after focal brain injury, (b) explain the neurophysiological effects of post-injury rehabilitative therapy on functional organization in motor cortex, (c) readers will be able to describe some of the variables that impact the effects of post-stroke behavioral experience on neuroplasticity, and (d) readers will be able to explain some of the current laboratory-based approaches to modifying brain circuits after stroke that might soon be translated to human application.     

Translating principles of neural plasticity into research on speech motor control recovery and rehabilitation.

PURPOSE: To review the principles of neural plasticity and make recommendations for research on the neural bases for rehabilitation of neurogenic speech disorders. METHOD: A working group in speech motor control and disorders developed this report, which examines the potential relevance of basic research on the brain mechanisms involved in neural plasticity and discusses possible similarities and differences for application to speech motor control disorders. The possible involvement of neural plasticity in changes in speech production in normalcy, development, aging, and neurological diseases and disorders was considered. This report focuses on the appropriate use of functional and structural neuroimaging and the design of feasibility studies aimed at understanding how brain mechanisms are altered by environmental manipulations such as training and stimulation and how these changes might enhance the future development of rehabilitative methods for persons with speech motor control disorders. CONCLUSIONS: Increased collaboration with neuroscientists working in clinical research centers addressing human communication disorders might foster research in this area. It is hoped that this article will encourage future research on speech motor control disorders to address the principles of neural plasticity and their application for rehabilitation.     

从中枢重塑阐述原发性耳鸣发病及治疗机制

原发性耳鸣的发病机制与多个脑网络中不同脑区的神经可塑性改变密切相关.由于长期异常信号的输入,细胞膜发生变化,突触活动发生改变,造成神经敏感性改变,逐渐引起中枢神经元的重塑.视觉网络、听觉网络、默认网络的各个脑区的中枢可塑性改变可能是耳鸣形成和维持的原因.西医、中医、中西医结合治疗均可改变各脑网络中不同脑区的神经兴奋性与...     

Predictors of spoken language learning

We report two sets of experiments showing that the large individual variability in language learning success in adults can be attributed to neurophysiological, neuroanatomical, cognitive, and perceptual factors. In the first set of experiments, native English-speaking adults learned to incorporate lexically meaningfully pitch patterns in words. We found those who were successful to have higher activation in bilateral auditory cortex, larger volume in Heschl's Gyrus, and more accurate pitch pattern perception. All of these measures were performed before training began. In the second set of experiments, native English-speaking adults learned a phonological grammatical system governing the formation of words of an artificial language. Again, neurophysiological, neuroanatomical, and cognitive factors predicted to an extent how well these adults learned. Taken together, these experiments suggest that neural and behavioral factors can be used to predict spoken language learning. These predictors can inform the redesign of existing training paradigms to maximize learning for learners with different learning profiles. LEARNING OUTCOMES: Readers will be able to: (a) understand the linguistic concepts of lexical tone and phonological grammar, (b) identify the brain regions associated with learning lexical tone and phonological grammar, and (c) identify the cognitive predictors for successful learning of a tone language and phonological rules.     

Auditory processing disorders: acquisition and treatment

Auditory processing disorder (APD) describes a mixed and poorly understood listening problem characterised by poor speech perception, especially in challenging environments. APD may include an inherited component, and this may be major, but studies reviewed here of children with long-term otitis media with effusion (OME) provide strong evidence for changes in auditory processing acquired through altered experience (deprivation) and brain plasticity. Whether inherited or acquired, it is suggested that APD may be reversed by active learning. Training tunes both bottom-up and top-down neural mechanisms, some that are specific to the trained stimulus and some that reflect more generalised arousal. APD and its treatment therefore provide examples of brain plasticity working either in a negative or in a positive way to modulate listening. LEARNING OUTCOMES: (1) Readers will be able to discuss APD in the context of inheritance and experience. (2) Readers will be able to explain how OME has been shown to alter auditory processing. (3) Readers will be able to list examples of good and bad brain plasticity. (4) Readers will be able to explain what auditory learning is, list some of its properties, and provide examples of its application in therapy for communication disorders.     

Improving the functioning of individuals with Alzheimer's disease: emergence of behavioral interventions

Alzheimer's disease (AD) is a neurodegenerative process that invariably results in diminished communicative functioning. Historically, it was thought that little could be done to improve the functioning of affected individuals. However, in recent years the value of behavioral interventions has increasingly been explored, resulting in a changing perspective. Some of the factors contributing to this changing view include: understanding that memory is not a unitary phenomenon, recognizing that certain types of memory are relatively spared in AD, a growing realization that conceptual knowledge is largely intact, and a greater understanding of how people learn and remember. Intervention techniques that capitalize on spared memory systems and take advantage of principles of learning and remembering have been successful in teaching individuals with AD new information and allowing them to maintain better functioning throughout the disease course. LEARNING OUTCOMES: (1) The participant will be able to describe the historical perspective on behavioral interventions, and four factors that have contributed to a changing perspective. (2) The participant will be able to list behavioral strategies that clinicians can use in order to improve functioning of individuals with AD.     

Short-term synaptic plasticity and intensity coding

Alterations in synaptic strength over short time scales, termed short-term synaptic plasticity, can gate the flow of information through neural circuits. Different information can be extracted from the same presynaptic spike train depending on the activity- and time-dependent properties of the plasticity at a given synapse. The parallel processing in the brain stem auditory pathways provides an excellent model system for investigating the functional implications of short-term plasticity in neural coding. We review recent evidence that short-term plasticity differs in different pathways with a special emphasis on the 'intensity' pathway. While short-term depression dominates the 'timing' pathway, the intensity pathway is characterized by a balance of short-term depression and facilitation that allows linear transmission of rate-coded intensity information. Target-specific regulation of presynaptic plasticity mechanisms underlies the differential expression of depression and facilitation. The potential contribution of short-term plasticity to different aspects of 'intensity'-related information processing, such as interaural level/intensity difference coding, amplitude modulation coding, and intensity-dependent gain control coding, is discussed.     

The role of central nervous system plasticity in tinnitus

Tinnitus is a vexing disorder of hearing characterized by sound sensations originating in the head without any external stimulation. The specific etiology of these sensations is uncertain but frequently associated with hearing loss. The "neurophysiogical" model of tinnitus has enhanced appreciation of central nervous system (CNS) contributions. The model assumes that plastic changes in the primary and non-primary auditory pathways contribute to tinnitus with the former perhaps sustaining them, and the latter contributing to perceived severity and emotionality. These plastic changes are triggered by peripheral injury, which results in new patterns of brain activity due to anatomic alterations in the connectivity of CNS neurons. These alterations may change the balance between excitatory and inhibitory brain processes, perhaps producing cascades of new neural activity flowing between brainstem and cortex in a self-sustaining manner that produces persistent perceptions of tinnitus. The bases of this model are explored with an attempt to distinguish phenomenological from mechanistic explanations. LEARNING OUTCOMES: (1) Readers will learn that the variables associated with the behavioral experience of tinnitus are as complex as the biological variables. (2) Readers will understand what the concept of neuroplastic brain change means, and how it is associated with tinnitus. (3) Readers will learn that there may be no one brain location associated with tinnitus, and it may result from interactions between multiple brain areas. (4) Readers will learn how disinhibition, spontaneous activity, neural synchronization, and tonotopic reorganization may contribute to tinnitus.     

Functional imaging of the central auditory system using PET

In the last few decades functional neuroimaging tools have emerged to study the function of the human brain in vivo. These techniques have increased the knowledge of how the brain processes stimuli of different sensory modalities, including auditory processing. Positron emission tomography (PET) has been used for nearly 20 years to study changes in cerebral blood flow associated with auditory stimulation in normal and hearing impaired subjects. PET studies gave insight into the neural base of processing basic sound features such as frequency and intensity, but complex stimuli such as speech and music have also been investigated extensively. Knowledge of the normal auditory function of the brain helps us to understand the neural base of hearing deficits and provides ideas for possible treatments. Although functional magnetic resonance imaging (fMRI) is replacing PET in many neuroimaging studies nowadays, PET still holds unique advantages and can give us valuable knowledge about the auditory cortex and auditory perception.     

Functional imaging of the central auditory system using PET

In the last few decades functional neuroimaging tools have emerged to study the function of the human brain in vivo. These techniques have increased the knowledge of how the brain processes stimuli of different sensory modalities, including auditory processing. Positron emission tomography (PET) has been used for nearly 20 years to study changes in cerebral blood flow associated with auditory stimulation in normal and hearing impaired subjects. PET studies gave insight into the neural base of processing basic sound features such as frequency and intensity, but complex stimuli such as speech and music have also been investigated extensively. Knowledge of the normal auditory function of the brain helps us to understand the neural base of hearing deficits and provides ideas for possible treatments. Although functional magnetic resonance imaging (fMRI) is replacing PET in many neuroimaging studies nowadays, PET still holds unique advantages and can give us valuable knowledge about the auditory cortex and auditory perception.     

Context-dependent modulation of auditory processing by serotonin

Context-dependent plasticity in auditory processing is achieved in part by physiological mechanisms that link behavioral state to neural responses to sound. The neuromodulator serotonin has many characteristics suitable for such a role. Serotonergic neurons are extrinsic to the auditory system but send projections to most auditory regions. These projections release serotonin during particular behavioral contexts. Heightened levels of behavioral arousal and specific extrinsic events, including stressful or social events, increase serotonin availability in the auditory system. Although the release of serotonin is likely to be relatively diffuse, highly specific effects of serotonin on auditory neural circuitry are achieved through the localization of serotonergic projections, and through a large array of receptor types that are expressed by specific subsets of auditory neurons. Through this array, serotonin enacts plasticity in auditory processing in multiple ways. Serotonin changes the responses of auditory neurons to input through the alteration of intrinsic and synaptic properties, and alters both short- and long-term forms of plasticity. The infrastructure of the serotonergic system itself is also plastic, responding to age and cochlear trauma. These diverse findings support a view of serotonin as a widespread mechanism for behaviorally relevant plasticity in the regulation of auditory processing. This view also accommodates models of how the same regulatory mechanism can have pathological consequences for auditory processing.     

Swallowing and dysphagia rehabilitation: translating principles of neural plasticity into clinically oriented evidence.

PURPOSE: This review presents the state of swallowing rehabilitation science as it relates to evidence for neural plastic changes in the brain. The case is made for essential collaboration between clinical and basic scientists to expand the positive influences of dysphagia rehabilitation in synergy with growth in technology and knowledge. The intent is to stimulate thought and propose potential research directions. METHOD: A working group of experts in swallowing and dysphagia reviews 10 principles of neural plasticity and integrates these advancing neural plastic concepts with swallowing and clinical dysphagia literature for translation into treatment paradigms. In this context, dysphagia refers to disordered swallowing associated with central and peripheral sensorimotor deficits associated with stroke, neurodegenerative disease, tumors of the head and neck, infection, or trauma. RESULTS AND CONCLUSIONS: The optimal treatment parameters emerging from increased understanding of neural plastic principles and concepts will contribute to evidence-based practice. Integrating these principles will improve dysphagia rehabilitation directions, strategies, and outcomes. A strategic plan is discussed, including several experimental paradigms for the translation of these principles and concepts of neural plasticity into the clinical science of rehabilitation for oropharyngeal swallowing disorders, ultimately providing the evidence to substantiate their translation into clinical practice.     

Tinnitus as a plastic phenomenon and its possible neural underpinnings in the dorsal cochlear nucleus

Tinnitus displays many features suggestive of plastic changes in the nervous system. These can be categorized based on the types of manipulations that induce them. We have categorized the various forms of plasticity that characterize tinnitus and searched for their neural underpinnings in the dorsal cochlear nucleus (DCN). This structure has been implicated as a possible site for the generation of tinnitus-producing signals owing to its tendency to become hyperactive following exposure to tinnitus inducing agents such as intense sound and cisplatin. In this paper, we review the many forms of plasticity that have been uncovered in anatomical, physiological and neurochemical studies of the DCN. Some of these plastic changes have been observed as consequences of peripheral injury or as fluctuations in the behavior and chemical activities of DCN neurons, while others can be induced by stimulation of auditory or even non-auditory structures. We show that many parallels can be drawn between the various forms of plasticity displayed by tinnitus and the various forms of neural plasticity which have been defined in the DCN. These parallels lend further support to the hypothesis that the DCN is an important site for the generation and modulation of tinnitus-producing signals.     

A translational approach to vocalization deficits and neural recovery after behavioral treatment in Parkinson disease

Parkinson disease is characterized by a complex neuropathological profile that primarily affects dopaminergic neural pathways in the basal ganglia, including pathways that modulate cranial sensorimotor functions such as swallowing, voice and speech. Prior work from our lab has shown that the rat model of unilateral 6-hydroxydopamine infusion to the medial forebrain bundle that is useful for studying limb sensorimotor deficits also yields vocalization deficits that may be amenable to treatment with intensive exercise. This affords us an opportunity to explore the potential mechanisms underlying behavioral and neural recovery as a result of intervention for cranial sensorimotor deficits associated with Parkinson disease. Our methods include recording and acoustic analysis of male rat ultrasonic vocalizations in a control condition, after neurotoxin infusion (Parkinson disease model), and after targeted vocalization training. We also use well-established behavioral and immunohistochemical methods to assess the level of neurochemical recovery in the striatum of the basal ganglia after our interventions. Our findings, although preliminary, prompt us to look in other brain regions extraneous to the striatum for potential underlying mechanisms of recovery. Thus, our future work will focus on the underlying mechanisms of behavioral recovery in a Parkinson disease model in the hope that this will lead to improved understanding of brain function and improved treatment for voice and swallowing disorders.Learning outcomes: Readers will gain an understanding of how a rat model of Parkinson disease is used to study vocalization deficits and interventions.     

NMDA受体与听觉发育可塑性及学习记忆研究的进展

NMDA受体是哺乳动物中枢神经系统主要的兴奋性氨基酸受体之一,对中枢神经系统许多重要的生理和病理过程,如神经网络的发育、突触可塑性、学习、记忆、神经退行性变等起着关键作用。神经系统的可塑性是发育神经生物学的重要研究领域之一,神经系统在发育过程中受环境因素和早期经验的影响表现出高度的可塑性。以长时程增强     

Searching for factors underlying cerebral plasticity in the normal and injured brain

Brain plasticity refers to the capacity of the nervous system to change its structure and ultimately its function over a lifetime. There have been major advances in our understanding of the principles of brain plasticity and behavior in laboratory animals and humans. Over the past decade there have been advances in the application of these principles to brain-injured laboratory animals. To date, there have been few major applications of this knowledge to establish postinjury interventions in humans. A significant challenge for the next 20 years will be the translation of this work to improve the outcome from brain injury and disease in humans. The goal of this review is to synthesize the multidisciplinary laboratory work on brain plasticity and behavior in the injured brain to inform the development of rehabilitation programs. LEARNING OUTCOMES: Readers will be able to: (a) identify principles of brain plasticity, (b) review the application of these principles to the treatment of brain-injured laboratory animals, and (c) consider the translation of the new treatments to brain-injured humans.