X-Message-Number: 14506 From: Eugene Leitl <> Date: Wed, 20 Sep 2000 01:42:28 -0700 (PDT) Subject: Scienceweek: ON BRAIN PLASTICITY AND STROKE 6. NEUROBIOLOGY: ON BRAIN PLASTICITY AND STROKE In human brain research, the term "plasticity" refers to the ability of various regions of the brain to assume specific functions as the result of experience, and also the ability of various regions of the brain to assume the functions of other regions that are damaged by disease or trauma ("adaptive plasticity"). Important questions concerning the biological basis of plasticity are a) What are the neural mechanisms responsible for plasticity? and b) What are the conditions which limit plasticity? Until recently, the primary source of evidence in this field was "anecdotal" -- evidence from individual clinical cases. That has changed: during the past decade, numerous studies have been carried out using non-invasive methods to monitor ongoing localized brain activity in conscious subjects, and evidence concerning plasticity and other characteristics of human brain function is rapidly mounting. ... ... N.P. Azari and R.J. Seitz (Heinrich Heine University, DE) present a review of current research in brain plasticity and recovery from stroke, the authors making the following points: 1) When a particular neural network is damaged, as often happens in a stroke, the system fails and function is initially lost because no other neurons in the brain are "wired" to do the task formerly performed by the damaged network. The result may be paralysis or the loss of speech or the inability to comprehend speech or any one of a number of actions. But many people who have suffered a stroke regain some or most of the lost functions after a brief recovery period, sometimes in a matter of weeks. 2) The capacity of the brain to reorganize itself -- its "plasticity" -- in the process of learning a task is perhaps the most interesting phenomenon that distinguishes the nervous system from all other tissues in the body. The plasticity of the brain appears to be greatest when we are young (from infancy through early adolescence), a time when many of the neural pathways that will be used for the acquisition of language and motor skills are formed. But our ability to learn new languages and new skills as adults indicates that the brain retains a certain level of plasticity throughout our lives (although our potential for learning new languages and skills may be decreased). 3) Many studies have shown that stroke patients require time to regain function. During this time, the brain is evidently sorting out how it might compensate for the damaged neurons, and the subsequent process of neural recovery appears to occur in several stages: ... ... a) Initially there is a passive tissue response in the first few hours and days following brain-tissue injury. This passive response involves the reperfusion of tissue deprived of blood-oxygen (ischemic tissue) and cessation of *inflammatory processes produced by brain damage. This leads to a regression of dysfunction associated with the temporary "shock" to the neurons in the vicinity of the lesion. Medical interventions that facilitate these early recovery processes determine the extent to which recovery will proceed to the subsequent stages. ... ... b) In the days and weeks following a stroke, the brain begins active processes of recovery involving adaptive plasticity. In the early stages, this may include intra-system pathways, if any have survived undamaged, pathways that normally play a mere supporting role in the undamaged brain. Since such pathways have previously been involved in the task, only task relearning is necessary, and this may explain why recovery is sometimes seen within a few weeks following a stroke. ... ... c) But if there is complete damage to a neural system, the brain may still have the capacity to recruit an alternative brain system, one not generally activated for the task by normal subjects. In such instances, the alternative system is naive to the task, so that the patient must relearn the task more or less completely. This requires more time, and evidence concerning alternative system pathways was until recently unavailable. 4) The authors conclude: "The existence of distinct stages in the recovery process has only become evident through the use of *functional imaging techniques. As the technology develops, we have little doubt that we will come to appreciate progressively finer aspects of adaptive plasticity and its role in a patient's recovery from brain lesions such as stroke." ----------- N.P. Azari and R.J. Seitz: Brain plasticity and recovery from stroke. (American Scientist Sep/Oct 2000 88:426) ----------- Text Notes: ... ... *inflammatory processes: In general, an "inflammatory change" is a response of tissues to irritation or injury. The response involves a dynamic complex of cellular and chemical reactions that occur in the affected blood vessels and adjacent tissues. ... ... *functional imaging techniques: The two main functional brain imaging techniques are *functional magnetic resonance imaging (fMRI) and *positron-emission tomography (PET). ... ... *functional magnetic resonance imaging (fMRI): We must first distinguish between magnetic resonance imaging (MRI) and "functional" magnetic resonance imaging (fMRI) as applied to the brain. The former is essentially a technique for examining morphology, while the latter is a technique for examining activity of brain tissue. Both techniques involve computerized analysis of data. In general, MRI involves magnetic coils producing a static magnetic field parallel to the long axis of the patient or subject, combined with inner concentric magnetic coils producing a static magnetic field perpendicular to the long axis. A radio-frequency coil specifically designed for the head perturbs the static fields to generate a magnetic resonance image. The interaction physics in this technique is that between the magnetic fields and atomic nuclei in brain tissue. "Sliced" views can be obtained from any angle, and the resolution is quite high and on the order of millimeters for current magnetic field strengths of 1.5 tesla. Functional magnetic resonance imaging (fMRI), the variant of MRI discussed here, is based on the fact that oxyhemoglobin, the oxygen-carrying form of hemoglobin, has a different magnetic resonance signal than deoxyhemoglobin, the oxygen-depleted form of hemoglobin. Activated brain areas utilize more oxygen, which transiently decreases the levels of oxyhemoglobin and increases the levels of deoxyhemoglobin, and within seconds the brain microvasculature responds to the local change by increasing the flow of oxygen-rich blood into the active area. This local response thus leads to an increase in the oxyhemoglobin-deoxyhemoglobin ratio, which forms the basis for the fMRI signal in this technique. Because of its high spatial resolution (millimeters) and high temporal resolution (seconds) compared to other imaging techniques, fMRI is now the technology of choice for studies of the functional architecture of the human brain. ... ... *positron-emission tomography (PET): This is a technique for producing cross-sectional images of the body after ingestion and systemic distribution of safely metabolized positron-emitting agents. The images are essentially functional or metabolic, since the ingested agents are metabolized in various tissues. Fluorodeoxyglucose and H(sub2)O(sup15) are common agents used for cerebral applications, and in cerebral applications of central importance to the technique is the fact that changes in the cellular activity of the brains of normal, awake humans and unanesthetized laboratory animals are invariably accompanied by changes in local blood flow and also changes in oxygen consumption. ------------------- Summary & Notes by SCIENCE-WEEK http://scienceweek.com 22Sep00 For more information: http://scienceweek.com/swfr.htm ------------------- Related Background: EVIDENCE OF CROSS-MODAL PLASTICITY IN BLIND HUMANS In neurobiology, the term "plasticity" is the name given to the capacity of neural tissue to adjust to change. One variant of this concerns the dependence of the "wiring" of the nervous system on its input. Another variant concerns the degree to which one region can under certain conditions assume the function of another region. Plasticity does not occur everywhere in the nervous system, but it is often evident in the cerebral cortex of the brain, the cortex being the thin layer of cells apparently responsible for higher analysis of sensory input, language, ideation, and other so-called higher functions lumped together in the category "cognitive processes". Last week Leonardo G. Cohen et al (11 authors at 4 installations in US, AR, JP) reported the results of studies of cross-modal plasticity in blind humans. These studies involved non-invasive interference with cortical activity by applying transient magnetic stimulation from outside the skull. It has been demonstrated that such stimulation can affect brain activity, and in this study the apparatus threshold for stimulation of the motor cortex was first determined, and then transient magnetic stimulation 10% above that threshold applied to the occipital lobes of the brain through the overlying skull to interfere with electrical activity in the visual cortex. The experiments involved various location and procedural controls, and also a group of sighted individuals. Essentially, what was found is that in people blind from an early age, the visual cortex is apparently involved in somato-sensory function (fingertip reading of individual Braille characters), while the same is not true for sighted subjects. ----------- QY: L. G. Cohen (Nature 11 Sep 97) (Science-Week 26 Sep 97) ------------------- Related Background: BRAIN PLASTICITY IN CHILDREN AFTER HEMISPHERECTOMY Epilepsy is a term unhappily applied to several dozen different seizure disorders, their commonality being central nervous system seizures rather than identical pathological processes causing the seizures. From a neurophysiological standpoint, a seizure is the end result of a massive discharge of nerve cells, often the motor neuron pathways that activate muscle cells. Seizures can be produced by various central nervous system infections, metabolic disturbances, toxic agents, cerebral oxygen deficiency, expanding brain lesions, cerebral trauma, cerebral hemorrhage, and so on. In general, any physiological event or series of events that produces a wide disruption of central nervous system activity has the potential for production of seizures of one sort or another. Most patients who for reasons known (symptomatic epilepsies) or unknown (idiopathic epilepsies) are chronically subjected to seizures can be helped with various pharmacological agents such as phenytoin or cloneazepam, but 10% to 20% of patients have seizures that cannot be managed by drugs. If the seizures are due to a specific damaged locus in the brain (the "epileptic focus"), the recourse for these patients, if the locus can be determined, is surgery. What is done is to completely remove the epileptic focus, sometimes an area no larger than a small coin, and if the surgery is successful the cure is immediate and permanent. There are cases, however, in which the affected part of the brain is quite large, the seizures completely unmanageable, and the only recourse is radical surgery. Since severe chronic epilepsy due to brain lesions is usually first diagnosed in young children, it is such children who are the usual patients in radical brain surgery for epilepsy. The most radical and fairly common procedure is hemispherectomy, removal of an entire half of the brain, and the most remarkable aspect of this is that when the surgical procedure is successful, not only are the seizures eliminated, but the child can function as well or almost as well as any other child. It is an example of a phenomenon well-known to neurobiologists called "brain plasticity", the ability of the brain to recover the function of a damaged or removed region by assignment of the function to an undamaged location. The language area of the brain, for example, is often considered to be fixed on the left side of the brain by genetics, but in truth it is not so fixed, and if the left side of the brain is removed at an early age, the right side of the brain will quickly develop a language center and there will be little functional impairment. In a recent publication, Eileen P.G. Vining (Johns Hopkins University, Baltimore MD US) reports the progress of 54 children who underwent hemispherectomy for recurrent severe epileptic seizures. The majority of the patients were seizure-free following surgery, no longer needed drugs, and many of the patients are now in school. One of the most significant facts about the human brain is that its histological development continues at least until adolescence, and the dynamism of this histological development is what is responsible for its remarkable plasticity. ----------- QY: E. Vining, Johns Hopkins University (410) 516-8171 (Pediatrics August 1997) (Science-Week 22 Aug 97) For more information: http://scienceweek.com/swfr.htm Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=14506