Patients suffering from schizophrenia display subtle cognitive abnormalities that may reflect a difficulty in rapidly coordinating the steps that occur in a variety of mental activities. Working interactively with the prefrontal cortex, the cerebellum may play a role in coordinating both motor and cognitive performance. This positron-emission tomography study suggests the presence of a prefrontal-thalamic-cerebellar network that is activated when normal subjects recall complex narrative material, but is dysfunctional in schizophrenic patients when they perform the same task. These results support a role for the cerebellum in cognitive functions and suggest that patients with schizophrenia may suffer from a "cognitive dysmetria" due to dysfunctional prefrontal-thalamic-cerebellar circuitry.

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.

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.

Automated identification of training classes for discriminant analysis was clearly superior to a method that required operator intervention. A sharp (discrete) classification into three tissue types was also slightly superior to one that used "fuzzy" classification to produce continuous measurements to correct for partial voluming. This multispectral automated discriminant analysis method produces a computationally efficient, reliable, and valid method for classifying brain tissue into GM, WM, and CSF. It corrects some of the problems with reliability and computational inefficiency previously observed for operator-dependent approaches to segmentation.

Short-term and long-term retention of experimentally presented words were compared in a sample of 33 healthy normal volunteers by the [150]H20 method with positron emission tomography (PET). The design included three conditions. For the long-term condition, subjects thoroughly studied 18 words 1 week before the PET study. For the short-term condition, subjects were shown another set of 18 words 60 sec before imaging, with instructions to remember them. For the baseline condition, subtracted from the two memory conditions, subjects read a third set ofwords that they had not previously seen in the experiment. Similar regions were activated in both short-term and long-term conditions: large right frontal areas, biparietal areas, and the left cerebellum. In addition, the short-term condition also activated a relatively large region in the left prefrontal region. These complex distributed circuits appear to represent the neural substrates for aspects of memory such as encoding, retrieval, and storage. They indicate that circuitry involved in episodic memory has much larger cortical and cerebellar components than has been emphasized in earlier lesion studies.Human memory is a complex phenomenon that has been variously conceptualized by cognitive neuroscientists, on the basis of data from lesion studies, animal experiments, and in vivo microelectrode stimulation of the human brain (1-9). Strength and ease of memory encoding and retrieval appear to be linked to a variety of factors, such as novelty of the information, amount of practice, duration and frequency of exposure, depth of processing, or the origin of the information and the relationship of the individual to it (i.e., intrinsic vs. extrinsic, participant vs. nonparticipant) (6,(10)(11)(12). A fundamental question embedded in memory research is whether memory is a unitary construct. Since the original subdivision into primary and secondary by William James, models have been developed to classify it in various ways, invoking constructs such as procedural vs. declarative, implicit vs. explicit, episodic vs. semantic, working vs. reference, or short-term vs. long-term (3, 6, 10-21). Modem cognitive neuroscience seeks to link these models to their neural substrates. In vivo neuroimaging techniques such as positron emission tomography (PET) have provided a new approach to studying these models by permitting measurement of physiological activity while the brain is performing specific tasks (13-27). While lesion studies in animals and humans permit inferences about brain organization by indicating what fails to work when parts of the brain have been damaged, neuroimaging studies permit inferences based on measuring changes in metabolic activity during performance of tasks that can be experimentally controlled.Here we report on a PET experiment designed to examine the neural substrates of recognition of previously learned verbal material. We compared long-term and short-term re-The publication costs of this article were defrayed in part by page charge payment. T...