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There are ongoing changes in the brains of schizophrenic patients during the initial years after diagnosis despite ongoing antipsychotic drug treatment. These progressive changes seem to be most evident in the frontal lobes and to correlate with functional impairment. Disruptions in neurodevelopment or neural plasticity may act alone or in combination to bring about these progressive brain deficits in schizophrenia.

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Schizophrenia is a complex illness characterized by multiple types of symptoms involving many aspects of cognition and emotion. Most efforts to identify its underlying neural substrates have focused on a strategy that relates a single symptom to a single brain region. An alternative hypothesis, that the variety of symptoms could be explained by a lesion in midline neural circuits mediating attention and information processing, is explored. Magnetic resonance images from patients and controls were transformed with a "bounding box" to produce an "average schizophrenic brain" and an "average normal brain." After image subtraction of the two averages, the areas of difference were displayed as an effect size map. Specific regional abnormalities were observed in the thalamus and adjacent white matter. An abnormality in the thalamus and related circuitry explains the diverse symptoms of schizophrenia parsimoniously because they could all result from a defect in filtering or gating sensory input, which is one of the primary functions of the thalamus in the human brain.

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Clinical observation suggests that the aging process affects gyrification, with the brain appearing more 'atrophic' with increasing age. Empirical studies of tissue type indicate that gray matter volume decreases with age while cerebrospinal fluid increases. Quantitative changes in cortical surface characteristics such as sulcal and gyral shape have not been measured, however, due to difficulties in developing a method that separates abutting gyral crowns and opens up the sulci -- the 'problem of buried cortex'. We describe a quantitative method for measuring brain surface characteristics that is reliable and valid. This method is used to define the gyral and sulcal characteristics of atrophic and non-atrophic brains and to examine changes that occur with aging in a sample of 148 normal individuals from a broad age range. The shape of gyri and sulci change significantly over time, with the gyri becoming more sharply and steeply curved, while the sulci become more flattened and less curved. Cortical thickness also decreases over time. Cortical thinning progresses more rapidly in males than in females. The progression of these changes appears to be relatively stable during midlife and to begin to progress some time during the fourth decade. Measurements of sulcal and gyral shape may be useful in studying the mechanisms of both neurodevelopmental and neurodegenerative changes that occur during brain maturation and aging.

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