Neonatal lesions of the medial temporal lobe disrupt prefrontal cortical regulation of striatal dopamine.

The effects of early brain damage are often, but not always, milder than the effects of comparable damage in adults, depending on the age at which injury occurred, the region of the brain damaged, and the brain functions involved. Studies of the impact of early brain damage have generally focused on functions primarily associated with the neural structures injured, even though the development and function of distant but interconnected neural systems might also show effects. Here we examine the regulation of striatal dopamine by the dorsolateral prefrontal cortex, in adult monkeys that had had either neonatal or adult lesions of the medial-temporal lobe and in normal animals.

Abnormal functional lateralization of the sensorimotor cortex in patients with schizophrenia.

Previous neuroimaging studies have suggested that patients with schizophrenia fail to recruit appropriate focal patterns of cortical responses to cognitive tasks. We investigated whether patients with schizophrenia show a normal focal response to a simple motor task. Seven strongly right-handed patients with schizophrenia and seven strongly right-handed normal subjects performed motor tasks of increasing complexity.

Genetic variability of human brain size and cortical gyral patterns.

The development of the primate brain is determined by an interaction of genetic programmes and environmental events. We examined quantitatively the contribution of each of these factors to adult human brain hemisphere volume and global cortical gyral patterns by comparing 3-D MRI renderings of brains of 10 pairs of monozygotic (MZ) and nine pairs of same-sex dizygotic (DZ) twins. Brain volume was highly correlated in MZ pairs [unbiased intraclass correlation coefficient, ICC(U) = 0.

The biological basis of schizophrenia: new directions.

The desire to understand the pathophysiology of schizophrenia has inspired an explosion in research over the past decade. This review highlights some key studies that have led to fundamental changes in our understanding of this disorder, focusing on the search for genes in schizophrenia, as well as several recent alternatives to the original dopamine hypothesis of schizophrenia. Advances in genetic methodology have allowed schizophrenia researchers to conduct genome-wide searches for susceptibility genes.

Cognitive activation during PET: a case study of monozygotic twins discordant for closed head injury.

Using positron emission tomography (PET), we studied physiological changes in a patient with frontal lobe damage resulting from closed head injury by assessing his regional cerebral blood flow (rCBF) pattern relative to that of his uninjured monozygotic (MZ) cotwin and against normal variability between cotwins in 10 comparably-aged, uninjured MZ twin pairs. rCBF was measured during the Wisconsin Card Sorting Test (WCST) and a sensorimotor control task. Differences between the index twins in rCBF activation (WCST-control) in regions determined on coplanar MRIs were compared to within-pair differences in the control group using the Z-statistic.

Physiological activation of a cortical network during performance of the Wisconsin Card Sorting Test: a positron emission tomography study.

To determine the neural circuitry engaged by performance of the Wisconsin Card Sorting Test (WCST), a neuropsychological test traditionally considered to be sensitive to prefrontal lesions, regional cerebral blood flow was measured with oxygen-15 water and positron emission tomography (PET) while young normal subjects performed the test as well as while they performed a specially designed sensorimotor control task. To consider which of the various cognitive operations and other experiential phenomena involved in the WCST PET scan are critical for the pattern of physiological activation and to focus on the working memory component of the test, repeat WCST scans were also performed on nine of the subjects after instruction on the test and practice to criteria. We confirmed that performance of the WCST engages the frontal cortex and also produces activation of a complex network of regions consistently including the inferior parietal lobule but also involving the visual association and inferior temporal cortices as well as portions of the cerebellum.

Brain imaging in schizophrenia.

Neuroimaging provides an unprecedented means by which to study psychiatric disorders. Structural imaging methods, i.e.

Regional cerebral blood flow in monozygotic twins discordant and concordant for schizophrenia.

We addressed several questions regarding hypofunction of the prefrontal cortex ("hypofrontality") in schizophrenia by measuring regional cerebral blood flow during three different cognitive conditions in monozygotic twins who were discordant or concordant for schizophrenia or who were both normal. These questions included the prevalence of hypofrontality, the importance of genetic predisposition, and the role of long-term neuroleptic treatment. Significant differences between affected and unaffected discordant twins were found only during a task linked to the prefrontal cortex, the Wisconsin Card Sorting Test.

Human cortical neuronal cell line (HCN-1): further in vitro characterization and suitability for brain transplantation.

The human neuronal cell-1 (HCN-1) line has recently been established. Under favorable conditions, these cells differentiate into mature neuronal phenotypes. Here we report on further characterization of these cells.