Diffusion-relaxation distribution functions of sedimentary rocks in different saturation states.

We present diffusion-relaxation distribution functions measured on four rock cores that were prepared in a succession of different saturation states of brine and crude oil. The measurements were performed in a static gradient field at a Larmor frequency of 1.76 MHz. The diffusion-relaxation distribution functions clearly separate the contributions from the two fluid phases. The results can be used to identify the wetting and non-wetting phase, to infer fluid properties of the phases, and to obtain additional information on the geometrical arrangement of the phases. We also observe effects due to restricted diffusion and susceptibility induced internal gradients.

T(1)--T(2) correlation spectra obtained using a fast two-dimensional Laplace inversion.

Spin relaxation is a sensitive probe of molecular structure and dynamics. Correlation of relaxation time constants, such as T(1) and T(2), conceptually similar to the conventional multidimensional spectroscopy, have been difficult to determine primarily due to the absense of an efficient multidimensional Laplace inversion program. We demonstrate the use of a novel computer algorithm for fast two-dimensional inverse Laplace transformation to obtain T(1)--T(2) correlation functions. The algorithm efficiently performs a least-squares fit on two-dimensional data with a nonnegativity constraint. We use a regularization method to find a balance between the residual fitting errors and the known noise amplitude, thus producing a result that is found to be stable in the presence of noise. This algorithm can be extended to include functional forms other than exponential kernels. We demonstrate the performance of the algorithm at different signal-to-noise ratios and with different T(1)--T(2) spectral characteristics using several brine-saturated rock samples.

Effects of olanzapine on cerebellar functional connectivity in schizophrenia measured by fMRI during a simple motor task.

BACKGROUND: According to current theories, schizophrenia results from altered connectivity in brain circuits for fundamental cognitive operations. Consequently, the poorly understood mechanisms of neuroleptic treatment may be explainable by altered functional interactions within such networks. The 'cognitive dysmetria' model hypothesizes that one key structure in these circuits is the cerebellum. To investigate the effects of olanzapine on cerebellar functional connectivity (CFC), a seed-voxel correlation analysis (SVCA) was used in a functional magnetic resonance imaging (fMRI) study of a simple finger-tapping task. METHODS: fMRI scans were obtained from six schizophrenic patients under both drug-free and olanzapine-treated conditions and from a matched control group of six healthy subjects at corresponding time points. SVCAs were performed for anatomically and functionally standardized seed voxels in the anterior cerebellum. SVCA results were then processed by three different randomization analyses. RESULTS: The analyses revealed that olanzapine caused widespread changes of CFC, including prominent changes in prefrontal cortex and mediodorsal thalamus. Significant changes in motor structures were found after subtractions within both groups and may thus indicate repetition effects rather than drug effects. Olanzapine 'normalized' the patients' CFC patterns for the right, but not for the left cerebellum. CONCLUSION: Even for a simple motor task, olanzapine affects functional interactions between the cerebellum and many non-motor brain regions, including elements of the 'cognitive dysmetria' circuit. Altogether, our findings suggest that olanzapine has a stronger differential effect on neural activity in prefrontal cortex and thalamus than in motor structures.

Anatomic and functional variability: the effects of filter size in group fMRI data analysis.

In the analysis of group fMRI scans, an optimal spatial filter should be large enough to accurately blend functionally homologous anatomic regions, yet small enough not to blur the functionally distinct regions. Hanning filters varying from 0.0 to 18.0 mm were evaluated in a group analysis of six healthy controls performing a simple finger-tapping paradigm. Test-retest reliability and Talairach-based measurements of the sensorimotor region were used to explore the optimal filter size. Two distinct regions of functional activation were noted in the sensorimotor cortex in group images (n = 6) at both time 1 and time 2. These regions merge once the filter size exceeds approximately 6.0 mm. The original hypothesis that these represented a motor and sensory activation was rejected on the basis of structural and functional variability. A discussion of the inherent difficulties in choosing an appropriate filter size is presented.

Acute marijuana effects on rCBF and cognition: a PET study.

The effects of smoking marijuana on cognition and brain function were assessed with PET using H2(15)O. Regional cerebral blood flow (rCBF) was measured in five recreational users before and after smoking a marijuana cigarette, as they repeatedly performed an auditory attention task. Blood flow increased following smoking in a number of paralimbic brain regions (e.g. orbital frontal lobes, insula, temporal poles) and in anterior cingulate and cerebellum. Large reductions in rCBF were observed in temporal lobe regions that are sensitive to auditory attention effects. Brain regions showing increased rCBF may mediate the intoxicating and mood-related effects of smoking marijuana, whereas reduction of task-related rCBF in temporal lobe cortices may account for the impaired cognitive functions associated with acute intoxication.

Untreated initial psychosis: its relation to quality of life and symptom remission in first-episode schizophrenia.

OBJECTIVE: Previous studies have suggested that there may be an association between longer duration of untreated psychosis and poor outcome in schizophrenia. These studies have been interpreted as providing evidence that untreated psychosis may constitute an "active morbid process" that is "toxic" to the brain. If untreated psychosis is neurotoxic, this would form a strong basis for early intervention in schizophrenia. METHOD: Seventy-four neuroleptic-naive patients with DSM-IV schizophrenia were evaluated 6 months after their first inpatient hospitalization. The authors examined the relationship between untreated initial psychosis duration (measured from onset of first symptom as well as from onset of full positive syndrome) and quality of life, symptom severity, and time to remission of positive symptoms. RESULTS: Earlier age at illness onset was associated with longer duration of untreated prodromal psychotic symptoms. There were no significant gender differences in duration of untreated initial psychosis, nor were there any significant associations between untreated initial psychosis duration and premorbid functioning. After controlling for the effects of age at onset, the duration of untreated initial psychosis did not significantly impair subsequent quality of life, symptom severity, or remission of positive symptoms. CONCLUSIONS: Duration of untreated initial psychosis was not prognostic of poor outcome early in the course of schizophrenia. Biological measures of neurotoxicity are needed to examine the "toxic psychosis" hypothesis more directly.

Cognitive correlates of the negative, disorganized, and psychotic symptom dimensions of schizophrenia.

Knowledge of the relationship between specific cognitive abnormalities and the clinical symptoms of schizophrenia could give insight into the nature of their underlying pathophysiology. Composite scores were generated for negative, disorganized, and psychotic symptom ratings in 134 patients with schizophrenia (DSM-IV criteria). Partial correlations (each composite corrected for the others) were computed with neuropsychological measures. Negative symptoms were related to poor performance on tests of verbal learning and memory, verbal fluency, visual memory, and visual-motor sequencing. Disorganized symptoms were correlated with lower verbal IQ and poor concept attainment. Psychotic symptoms had no significant relationship with cognitive deficit.

Sexual dimorphism in the human brain: evaluation of tissue volume, tissue composition and surface anatomy using magnetic resonance imaging.

Magnetic resonance imaging (MRI) was used to evaluate sex differences in brain morphology by comparing measures of brain tissue volume, brain tissue composition (proportions of gray and white matter), and measures of cortical surface anatomy. A large and well-matched sample of healthy women (n=42) and healthy men (n=42) were evaluated. There was a significant gender effect on intracranial volume, males being larger. However, this increase in size was limited to the cerebrum as there was no sex difference in the volume of the cerebellum. The gender difference in size of the cerebral volume was evenly distributed, with all four lobes equally larger in males compared to females. Gray and white matter tissue proportions were similar between the sexes globally. Regional tissue composition analysis showed sex differences within the parietal lobes with females having proportionately more gray matter on the right side. There were no differences between the sexes in cortical surface anatomy measures. Overall, against the background of similarity in morphology, there are differences between the sexes with regard to general and regional brain measures. The functional significance of these sex differences is unclear, but may represent the differential effects of gonadal hormones during brain growth and development.

Defining the phenotype of schizophrenia: cognitive dysmetria and its neural mechanisms.

All research on schizophrenia depends on selecting the correct phenotype to define the sample to be studied. Definition of the phenotype is complicated by the fact that there are no objective markers for the disorder. Further, the symptoms are diverse, leading some to propose that the disorder is heterogeneous and not a single disorder or syndrome. This article explores an alternative possibility. It proposes that schizophrenia may be a single disorder linked by a common pathophysiology (a neurodevelopmental mechanism), which leads to a misconnection syndrome of neural circuitry. Evidence for disruption in a specific circuit is explored: the cortical-thalamic-cerebellar-cortical circuit (CCTCC). It is suggested that a disruption in this circuit leads to an impairment in synchrony, or the smooth coordination of mental processes. When synchrony is impaired, the patient suffers from a cognitive dysmetria, and the impairment in this basic cognitive process defines the phenotype of schizophrenia and produces its diversity of symptoms.

Quantitative in vivo measurement of gyrification in the human brain: changes associated with aging.

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.

Prevalence of depressive symptoms early in the course of schizophrenia.

OBJECTIVE: The rate of depressive symptoms early in the course of schizophrenia was determined. METHOD: Seventy subjects with recent-onset schizophrenia were followed for 5 years by using semistructured interview instruments. The initial assessment included ratings of each criterion A symptom of a DSM-III-R major depressive episode. The rates of symptoms experienced with at least moderate severity were calculated, and an algorithm based on DSM identified subjects meeting the criteria for a major depressive episode. RESULTS: Four symptoms were present to at least a moderate degree in a majority of subjects, while no symptom was present in fewer than 12% of subjects. More than one-third of the subjects met the algorithmic criteria for a major depressive episode at the time of intake. CONCLUSIONS: Depressive symptoms are common early in the course of schizophrenia. This finding is consistent with other recent data and has potential implications for current diagnostic and treatment practices.

Cerebellar morphology as a predictor of symptom and psychosocial outcome in schizophrenia.

BACKGROUND: In this study, we examined whether brain morphology assessed early in the course of schizophrenia predicted psychosocial or symptomatic outcome. METHODS: We acquired magnetic resonance images on 63 subjects with schizophrenia spectrum disorders and manually traced regions of interest, including the cerebrum, temporal lobes, ventricles, and cerebellum. Subjects were then prospectively assessed every 6 months for an average of 7 years. Outcome symptom measures were longitudinal rather than cross-sectional, and included average number of weeks per year spent in a psychotic negative, or disorganized symptom syndrome, and average number of weeks of inpatient treatment per year. A psychosocial outcome measure summed ratings of impairment in employment, recreation, sexual activity, and interpersonal relationships. RESULTS: Negative associations were found between cerebellar volume and three outcome measures: negative and psychotic symptom duration, and psychosocial impairment. CONCLUSIONS: These results underscore the potential role of cerebellar abnormalities in the etiology and pathophysiology of schizophrenia.

Preoperative predictors of cost in Medicare-age patients undergoing coronary artery bypass grafting.

BACKGROUND: Identification of preoperative factors that contribute to the cost of coronary artery bypass grafting could aid in predicting the procedure's expense. In this study, 30 sociodemographic and clinical preoperative factors were examined with "survival analysis" techniques to determine characteristics related to total hospital cost. METHODS: Characteristics of all patients age 65 or older undergoing isolated coronary artery bypass grafting from July 1993 to April 1995 (n = 757) were recorded. Software was developed within the hospital's Transitions Systems, Inc, database to calculate the outcome variable of total cost. Nonparametric methods were used for the univariate analysis of the data, and the Cox proportional hazards model was used for the multivariable analysis, censoring 25 patients who died in the hospital. RESULTS: Median hospital cost from the day of the operation until discharge was $15,198. Median length of stay after the operation was 6 days. Multivariable analysis revealed that age, preoperative renal failure, history of cerebrovascular accident, low ejection fraction, and surgical urgency were independent predictors of total cost. CONCLUSIONS: This study, using an accurate representation of true hospital cost and a modeling technique that accounts for the confounding effect of in-hospital death on cost, provides a template for analysis of cost in other patient groups.

Two-year outcome in first-episode schizophrenia: predictive value of symptoms for quality of life.

OBJECTIVE: Many studies have validated the grouping of schizophrenic symptoms into three independent dimensions: negative, psychotic, and disorganized. Negative symptoms are considered to be an important prognostic indicator, but this clinical observation requires further empirical study, especially with respect to psychosocial functioning. When present at the onset of the first episode, negative symptoms suggest that the patient will develop significant psychosocial impairment. The predictive values of the psychotic and disorganized symptom dimensions, on the other hand, have been less certain. METHOD: In this study of 50 first-episode schizophrenic patients, who were mostly neuroleptic-naive at intake, the authors examined the relationship between the severity of these three symptom dimensions (measured by using the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms) at index hospitalization and quality of life at 2-year follow-up. RESULTS: Negative symptom severity was positively and significantly correlated with later occupational impairment, financial dependence on others, impaired relationships with friends, impaired ability to enjoy recreational activities, and global assessment of functioning. The magnitudes of correlation between the levels of psychotic symptoms or disorganized symptoms and 2-year quality of life measures were comparatively lower. Analyses using multivariate regression statistics also revealed similar findings. CONCLUSIONS: Severity of negative symptoms at index hospitalization may be a portent of poor outcome. In general, severity of psychotic or disorganized symptoms at intake does not appear to predict subsequent quality of life.

Incidence of ectopic gray matter in patients with schizophrenia and healthy control subjects studied with MRI.

Magnetic resonance imaging scans were visually inspected to investigate the incidence of gray matter heterotopia (GMH) in a group of 55 schizophrenic patients and a group of 75 control subjects. No GMHs were found in the control subjects. In the patient group, 1 GMH was found, an incidence of 1.8%.

Functional MRI statistical software packages: a comparative analysis.

Currently, there are many choices of software packages for the analysis of fMRI data, each offering many options. Since no one package can meet the needs of all fMRI laboratories, it is helpful to know what each package offers. Several software programs were evaluated for comparison of their documentation, ease of learning and use, referencing, data input steps required, types of statistical methods offered, and output choices. The functionality of each package was detailed and discussed. AFNI 2.01, SPM96, Stimulate 5.0, MEDIMAX 2.01, and FIT were tested. FIASCO, Yale, and MEDx 2.0 were described but not tested. A description of each package is provided.

Morphometry in schizophrenia revisited: height and its relationship to pre-morbid function.

BACKGROUND: Morphometry, the measurement of forms, is an ancient practice. In particular, schizophrenic somatology was popular early in this century, but has been essentially absent from the literature for over 30 years. More recently, evidence has grown to support the notion that aberrant neurodevelopment may play a role in the pathophysiology of schizophrenia. Is the body, like the brain, affected by abnormal development in these patients? METHODS: To evaluate global deficit in development and its relationship to pre-morbid function, height was compared in a large group (N = 226) of male schizophrenics and a group of healthy male controls (N = 142) equivalent in parental socio-economic status. Patients in the lower quartile of height were compared to those in the upper quartile of height. RESULTS: The patient group had a mean height of 177.1 cm, which was significantly shorter than the mean height of the control group of 179.4 (P < 0.003). Those in the lower quartile had significantly poorer pre-morbid function as measured by: (1) psychosocial adjustment using the pre-morbid adjustment scales for childhood and adolescence/young adulthood, and (2) cognitive function using measures of school performance such as grades and need for special education. In addition, these measures of pre-morbid function correlated significantly with height when analysed using the entire sample. CONCLUSIONS: These findings provide further support to the idea that abnormal development may play a key role in the pathophysiology of schizophrenia. Furthermore, this is manifested as a global deficit in growth and function resulting in smaller stature, poorer social skills, and deficits in cognitive abilities.

Sex differences in brain morphology in schizophrenia.

OBJECTIVE: The current literature on sex differences in schizophrenia with regard to structural brain abnormalities is inconsistent. Several studies have suggested that male and female patients may differ in severity of brain abnormalities. Efforts to explore this issue have been hindered by small study groups, unbalanced groups (i.e., those with many more men than women), or both. The relatively smaller number of female schizophrenic patients in most studies may have made it more difficult to detect differences between patients and comparison subjects. This study was designed to evaluate brain morphology in a carefully selected group of patients with schizophrenia and healthy comparison subjects who were balanced by sex. METHOD: Eighty patients (40 male and 40 female) and 80 healthy volunteers matched by sex and age were studied. Magnetic resonance imaging scans were analyzed with the use of an automated method that yields volumes of major brain regions. RESULTS: There was a significant sex-by-diagnosis interaction for ventricular volume, with male patients having significantly larger ventricles than male comparison subjects but female patients showing no significant enlargement in comparison with healthy female subjects. Although the overall distribution of structural brain differences was very similar in the male and female patients, the male patients had a greater number of significant abnormalities than the female patients. CONCLUSIONS: These findings indicate that male and female patients with schizophrenia have the same pattern of structural brain abnormalities, but male patients appear to manifest greater severity, especially with regard to ventricular enlargement.