Showing papers in "Advances in Neurology in 1998"

A new view of specific and nonspecific thalamocortical connections

Abstract: Past theories about the circuitry that promotes integration of the whole cerebral cortex and thalamus during forebrain activities that underlie different states of consciousness have relied on the intralaminar nuclei as the sources of diffuse thalamocortical projections that could facilitate spread of activity across many cortical areas. Evidence is presented to show the presence of a matrix of superficially projecting cells extending throughout the whole thalamus that could form a substrate for diffusion of activity across the cortex. The superficially projecting cells in monkeys are distinguished by immunoreactivity for the calcium-binding protein calbindin. They are found in all thalamic nuclei and are increased in some nuclei. They not only project to superficial layers of the cortex but do so over wide areas, unconstrained by boundaries between areas. They are innervated by subcortical inputs that lack the topographic order and physiological precision of the principal sensory pathways. Superimposed on the matrix, but only in certain nuclei, is a core of cells characterized by immunoreactivity for another calcium-binding protein, parvalbumin. These project to middle layers of the cortex in an area-specific and topographically ordered manner. They are innervated by subcortical inputs that are typically precise in having a high degree of topographic order and readily identifiable physiological properties. The parvalbumin cells provide the sensory and other inputs to the cortex that are to be used as a basis for perception. The diffusely projecting calbindin cells can form a basis for the engagement of multiple cortical areas and thalamic nuclei, especially when recruited by corticothalamic connections. Diffusion of activity across multiple areas and thalamic nuclei is essential for the binding of all aspects of sensory experience into a single framework of consciousness.

The National Institutes of Health Anticonvulsant Drug Development Program: screening for efficacy.

Abstract: The procedures employed by the ASP provide detailed information pertaining to the anticonvulsant profile of new candidate substances. In addition, the results obtained from tolerance and liver microsomal studies furnish critical information for predicting whether tolerance and/or serious drug-drug interactions are likely to develop following long-term administration of a candidate substance. Finally, in vitro mechanism-of-action studies supply preliminary information regarding the site of action of promising new anticonvulsant drugs. It is anticipated that the testing protocol outlined above will identify safer and mechanistically novel substances to enhance significantly the quality of life of those epilepsy patients still suffering from uncontrolled seizure disorders and/or experiencing significant adverse drug effects.

Brain and conscious experience.

Abstract: There is a deep belief that we can attain not only a neuroscience of consciousness but a neuroscience of human consciousness. It is as if something terribly new and complex happens as the brain enlarges to its human form. Whatever this is, it triggers our capacity for self-reflection, for ennui, and for lingering moments, I would like to propose a simple, three-step suggestion. First, we should focus on what we mean when we talk about conscious experience. It is merely the awareness we have of our capacities as a species, but not the capacities themselves--only the awareness or feelings we have about them. The brain is clearly not a general purpose computing device but is a collection of circuits devoted to quite specific capacities. This is true for all brains, but what is wonderful about the human brain is that we have untold numbers of these capacities. We have more than the chimp, which has more than the monkey, which has more than the cat, which runs circles around the rat. Because we have so many specialized systems and because they can frequently do things they were not designed to do, it appears our brains have a single, general computing device. But we do not. Thus, step 1 requires that we recognize we are a collection of adaptations and, furthermore, we recognize the distinction between a species' capacities and its feelings about those capacities. Now consider step 2. Can there be any doubt that a rat at the moment of copulation is as sensorially fulfilled as a human? Of course it is. Do you think a cat does not enjoy a good piece of cod? Of course it does. Or, a monkey does not enjoy a spectacular swing? Again, it has to be true. Each species is aware of its special capacities. So, what is human consciousness? It is the very same awareness, save for the fact that we can be aware of so much more, so many wonderful things. A circuit--perhaps a single system or one duplicated over and over again--is associated with each brain capacity. The more systems a brain possesses, the greater the awareness of capacities. Think of the variations in capacity within our own species; they are not unlike the vast differences between species. Years of split-brain research have informed us that the left hemisphere has many more mental capacities than the right one. The left is capable of logical feats that the right hemisphere cannot manage. Although the right has capacities such as facial recognition systems, it is a distant second with problem-solving skills. In short, the right hemisphere's level of awareness is limited. It knows precious little about a lot of things, but the limits to human capacity are everywhere in the population. No one need be offended to realize that just as someone with normal intelligence can understand Ohm's law, others, like yours truly, are clueless about Kepler's laws. I am ignorant about them and will remain so. I am unable to be aware about what they mean for the universe. The circuits that enable me to understand these things are not present in my brain. By emphasizing specialized circuits that arise from natural selection, we see that the brain is not a unified neural net that supports a general problem-solving device. With this being understood, we can concentrate on the possibility that smaller, more manageable circuits produce awareness of a species' capacities. Holding fast to the notion of a unified neural net means we can understand human conscious experience only by figuring out the interactions of billions of neurons. That task is hopeless. My scheme is not. Hence step 3. The very same split-brain research that exposed shocking differences between the two hemispheres also showed that the human left hemisphere has the interpreter. The left brain interpreter's job is to interpret our behavior and our responses, whether cognitive or emotional, to environmental challenges. It constantly establishes a running narrative of our actions, emotions, thoughts, and dreams. It is the glue that keeps our

Fixation-off, scotosensitive, and other visual-related epilepsies.

Abstract: FOS is a relatively recently described specific mode of precipitation of seizures and paroxysmal EEG abnormalities. Elimination of central vision and fixation, even in the presence of light, induces high-amplitude occipital or generalized paroxysmal discharges. FOS is suggested on routine EEG by abnormalities that consistently occur as long as the patient's eyes are closed but not when the eyes are open. The model example of FOS is early-onset and late-onset BCEOP. Idiopathic and cryptogenic generalized epilepsies with FOS have been described. Scotosensitive epilepsy implies seizures and EEG abnormalities induced by the complete elimination of retinal light stimulation, and most cases described as scotosensitive are probably FOS. FOS has characteristics opposite to those of photosensitive epilepsies, but conversion from one to the other or co-existence may rarely occur. The underlying mechanisms of FOS are not known, but they may be related to an abnormality of the alpha-rhythm generators.

Reflex epilepsies and reflex seizures

Abstract: An examination of every aspect of reflex seizures and reflex epilepsy by an international group of experts in epileptology and clinical neurophysiology. It discusses definition, classification, experimental models, mechanisms of seizure induction, and evoked responses in reflex epilepsy to investigation of patients and evaluation and management of specific syndromes. The coverage of photosensitive epilepsy includes experimental and pathophysiologic studies; genetics, epidemiology and electroencephalographic considerations; seizures induced by flicker; seizures induced by patterns, TV and video games; and self-induced seizures.

New drugs for persons with epilepsy.

Abstract: Between 30% and 60% of patients with epilepsy have not achieved adequate control with current medications, and side effects are a significant problem. In the past 2 years, three drugs for epilepsy have been approved. At least six more drugs are in the final stages of development, and there is an active "pipeline." None of the new drugs are panceas, but many have special advantages and meet important specific needs. Felbamate, despite a high incidence of aplastic anemia and hepatic failure, remains useful because of its lack of sedative effects and high efficacy. Gabapentin is remarkable for its favorable side effect profile, lack of interactions, and straightforward kinetics. Lamotrigine is also nonsedating and may be especially useful in generalized epilepsies. Topiramate and vigabatrin are both highly effective, although each is associated with a variety of cognitive or psychiatric side effects that may limit utility. Oxcarbazepine shares the efficacy of carbamazepine, with fewer side effects or drug interactions. Zonisamide seems to be effective and cause mild side effects, although the risk for renal stones indicates a need for cautious use. Tiagabine, like gabapentin, is a mild drug with a favorable side effect profile. New forms of old drugs will make for easier administration; fosphenytoin will increase the safety of parenchymal phenytoin use. The best of the new drugs help, at most, 10% of previously uncontrolled patients to become seizure-free. The development of new drugs remains an important need.