Several studies suggest that the nonschizophrenic relatives of schizophrenic patients exhibit structural brain abnormalities that may be manifestations of genes that predispose to schizophrenia. In this work, we examine the utility of such measures for linkage analyses. Subjects were 45 nonpsychotic first-degree adult relatives of schizophrenic patients and 48 normal controls. Sixty contiguous 3-mm coronal, T1-weighted 3D magnetic resonance images of the entire brain were acquired on a 1.5-T magnet. We used factor analysis to derive MRI-based phenotypes for analysis. The factor analyses produced three factors that significantly discriminated relatives from controls. We used a linear combination of the three factor scores to derive an MRI phenotype. A receiver operating characteristic (ROC) analysis of this phenotype estimated an area under the curve (AUC) statistic of 0.85. The phenotype also discriminated nonpsychotic relatives having two schizophrenic relatives from those having only one. The nonpsychotic relatives of schizophrenic patients show deviant values on MRI measures of brain structure and the distribution of these deviations among relatives and controls suggests that if these results can be replicated, an MRI-derived phenotype could be useful for genetic linkage and association analyses.
A central question in schizophrenia research is which brain abnormalities are independent of psychosis and which evolve before and after psychosis begins. This question can be addressed by longitudinal neuroimaging studies beginning in the prodrome, but at present there is only one published study. We reviewed the literature on structural brain imaging in persons with chronic and first episode schizophrenia, nonpsychotic persons at genetic high risk, and persons thought to be at risk for imminent psychosis ("prodromal" persons). Medial temporal lobe (MTL), especially hippocampal, volume alterations are among the most robust brain vulnerabilities for schizophrenia. Because verbal declarative memory (VDM) deficits are prominent and the parahippocampal gyrus (PHG) is considered to be centrally involved with the hippocampus in VDM processing, we analyzed PHG data from a family study of schizophrenia. Patients with schizophrenia and nonpsychotic relatives from "multiplex" families (families with multiple persons with schizophrenia) had significantly smaller right parahippocampal anterior (PHa) volumes than controls. Marginally significant findings were observed for the left PHa. Unexpectedly, relatives from "simplex" families (families with only one person with schizophrenia) had significantly larger PH posterior volumes than controls and did not differ from controls on PHa. Results provide some support for the hypothesis that the vulnerability to schizophrenia includes abnormal volumes of the PHG. These data provide additional support for the hypothesis that some MTL abnormalities in schizophrenia are independent of psychosis, at least in families with presumably high genetic loading. Implications of genetic risk studies for prodromal research are discussed.
STUDY OBJECTIVES: While obesity is the most common risk factor for the development of obstructive sleep apnea, the correlation between measures of obesity and apnea severity is only moderate. We thus attempted to identify anatomic and physiologic predictors of apnea severity.
DESIGN: We combined a careful assessment of upper airway anatomy, upper airway physiology, and ventilatory control in a group of obese individuals to identify predictors of apnea severity.
SETTING: Tertiary care academic medical center.
PATIENTS: 14 morbidly obese subjects being evaluated for weight-reduction surgery.
INTERVENTIONS: N/A MEASUREMENT AND RESULTS: We found no relationship between obesity (weight or body mass index) and apnea severity (respiratory disturbance index, RDI). However, those with severe apnea (RDI > 30) were found to have higher peak genioglossus EMG (GGEMG) (23.5 +/- 1.9 vs. 14.1 +/- 3.7 %max, p = 0.05) and greater airway collapsibility during pulses of negative pressure (7.6 +/- 0.9 vs. 4.4 -/+/-0.7 cmH2O, p =0.02). Airway collapsibility was significantly associated with RDI (r = 0.62, p < 0.01) as was peak GGEMG (r = 0.55, p < 0.05). Of the anatomic variables airway shape (A-P/lateral ratio) and volume change of the pharyngeal airway between total lung capacity and residual volume were different between those with and without severe apnea. Both correlated with RDI (A-P/lateral ratio: r = 0.70, p < 0.01 and volume change: r = 0.77, p < 0.01).
CONCLUSIONS: We believe these findings suggest that specific anatomic and physiologic properties of the airway interact with obesity to predispose to the development of airway collapse during sleep.
The signal obtained with q-space NMR imaging applied to a confined liquid is directly related to the pore shape in the limit where all molecules have sampled the whole pore. We investigate the diffusion of water across a approximately 50 microm thick film formed between planes of glass. The diffusion time t is changed almost three orders of magnitude. For short t, the root-mean-square displacement increases with a rate which is slightly less than for freely diffusing water. At t longer than 0.3 s, the displacement is constant at 24 microm which implies that the water is confined in the measuring direction defined by the applied gradient pulses. Perfectly smooth and aligned planes give rise to sharp diffraction-like features on the echo attenuation curve, i.e., NMR signal vs. the reciprocal space vector q. The experimental data with rather smooth local minima and maxima can be explained in terms of either surface roughness or a misalignment of the planes. We discuss the averaging effect of diffusion along a laterally inhomogeneous film and propose two model-free methods to determine the pore shape from the echo attenuation curve obtained in the long-t limit.
BACKGROUND: The fusiform gyrus (FG), or occipitotemporal gyrus, is thought to subserve the processing and encoding of faces. Of note, several studies have reported that patients with schizophrenia show deficits in facial processing. It is thus hypothesized that the FG might be one brain region underlying abnormal facial recognition in schizophrenia. The objectives of this study were to determine whether there are abnormalities in gray matter volumes for the anterior and the posterior FG in patients with chronic schizophrenia and to investigate relationships between FG subregions and immediate and delayed memory for faces.
METHODS: Patients were recruited from the Boston VA Healthcare System, Brockton Division, and control subjects were recruited through newspaper advertisement. Study participants included 21 male patients diagnosed as having chronic schizophrenia and 28 male controls. Participants underwent high-spatial-resolution magnetic resonance imaging, and facial recognition memory was evaluated. Main outcome measures included anterior and posterior FG gray matter volumes based on high-spatial-resolution magnetic resonance imaging, a detailed and reliable manual delineation using 3-dimensional information, and correlation coefficients between FG subregions and raw scores on immediate and delayed facial memory derived from the Wechsler Memory Scale III.
RESULTS: Patients with chronic schizophrenia had overall smaller FG gray matter volumes (10%) than normal controls. Additionally, patients with schizophrenia performed more poorly than normal controls in both immediate and delayed facial memory tests. Moreover, the degree of poor performance on delayed memory for faces was significantly correlated with the degree of bilateral anterior FG reduction in patients with schizophrenia.
CONCLUSION: These results suggest that neuroanatomic FG abnormalities underlie at least some of the deficits associated with facial recognition in schizophrenia.
OBJECTIVE: Smaller temporal lobe cortical gray matter volumes, including the left superior temporal gyrus, have been reported in magnetic resonance imaging (MRI) studies of patients with chronic schizophrenia and, more recently, in patients with first-episode schizophrenia. However, it remains unknown whether there are progressive decreases in temporal lobe cortical gray matter volumes in patients with first-episode schizophrenia and whether similarly progressive volume decreases are present in patients with affective psychosis.
METHOD: High-spatial-resolution MRI scans at initial hospitalization and 1.5 years later were obtained from 13 patients with first-episode schizophrenia, 15 patients with first-episode affective psychosis (mainly manic), and 14 healthy comparison subjects. MRI volumes were calculated for gray matter of superior temporal gyrus and for the amygdala-hippocampal complex.
RESULTS: Patients with first-episode schizophrenia showed significant decreases in gray matter volume over time in the left superior temporal gyrus compared with patients with first-episode affective psychosis or healthy comparison subjects. This progressive decrease was more pronounced in the posterior portion of the left superior temporal gyrus (mean=9.6%) than in the anterior portions (mean=8.4%). No group differences in the rate of change over time were present in other regions.
CONCLUSIONS: These findings demonstrate a progressive volume reduction of the left posterior superior temporal gyrus gray matter in patients with first-episode schizophrenia but not in patients with first-episode affective psychosis.
Virtual cystoscopy is a developing technique for bladder cancer screening. In a conventional cystoscopy, an optical probe is inserted into the bladder and an expert reviews the appearance of the bladder wall. Physical limitations of the probe place restrictions on the examination of the bladder wall. In virtual cystoscopy, a computed tomography (CT) scan of the bladder is acquired and an expert reviews the appearance of the bladder wall as shown by the CT. The task of identifying tumors in the bladder wall has often been done without extensive computational aid to the expert. We have developed an image processing algorithm that aids the expert in the detection of bladder tumors. Compared with an expert observer reading the CT, our algorithm achieves 89% sensitivity, 88% specificity, 48% positive predictive value, and 98% negative predictive value.
Schizophrenia has been conceptualized as a failure of cognitive integration, and abnormalities in neural circuitry (particularly inhibitory interneurons) have been proposed as a basis for this disorder. We used measures of phase locking and phase coherence in the scalp-recorded electroencephalogram to examine the synchronization of neural circuits in schizophrenia. Compared with matched control subjects, schizophrenia patients demonstrated: (1) absence of the posterior component of the early visual gamma band response to Gestalt stimuli; (2) abnormalities in the topography, latency, and frequency of the anterior component of this response; (3) delayed onset of phase coherence changes; and (4) the pattern of anterior-posterior coherence increases in response to Gestalt stimuli found in controls was replaced by a pattern of interhemispheric coherence decreases in patients. These findings support the hypothesis that schizophrenia is associated with impaired neural circuitry demonstrated as a failure of gamma band synchronization, especially in the 40 Hz range.
This article introduces novel and fundamental improvements of fMRI data analysis. Central is a technique termed constrained canonical correlation analysis, which can be viewed as a natural extension and generalization of the popular general linear model method. The concept of spatial basis filters is presented and shown to be a very successful way of adaptively filtering the fMRI data. A general method for designing suitable hemodynamic response models is also proposed and incorporated into the constrained canonical correlation approach. Results that demonstrate how each of these parts significantly improves the detection of brain activity, with a computation time well within limits for practical use, are provided.
We developed a computer model to simulate associative memory recall of patients with chronic schizophrenia. Model inputs consisted of words derived from normative data that differed in terms of connectivity and network size, with the former quantitatively represented by parametric weights and the latter by the specific number of word associates that formed a particular network. Previous behavioral studies of normal subjects indicated better recall for words of high connectivity-small network (HCSN), followed by low connectivity-small network (LCSN), high connectivity-large network (HCLN), and low connectivity-large network (LCLN). This pattern of recall differed from that observed in behavioral studies of schizophrenic patients, which showed better recall for high connectivity words, regardless of network size. Holding constant network size while manipulating connection weights effectively simulated this schizophrenic pattern of recall. That is, manipulation of parametric weights coupled with a slight increase in noise significantly and reliably elicited the response pattern of abnormal connectivity demonstrated in the prior behavioral study of patients with chronic schizophrenia. An increase in noise was a necessary, but insufficient step in modeling the response pattern of abnormal connectivity. These findings provide support for the use of computational models to investigate dynamics of associative word recall in patients with chronic schizophrenia.
CONTEXT: Whether psychoses associated with schizophrenia and affective disorder represent manifestations of different disorders or the same disorder is an important but unresolved question in psychiatry. Results of previous volumetric magnetic resonance imaging investigations indicate that gray matter volume reductions in neocortical regions may be specific to schizophrenia.
OBJECTIVE: To simultaneously evaluate multiple olfactocentric paralimbic regions, which play crucial roles in human emotion and motivation, in first-episode patients with schizophrenia and affective psychosis.
DESIGN: A cross-sectional study using high-spatial resolution magnetic resonance imaging in patients with schizophrenia and affective psychosis at their first hospitalization.
SETTING: Inpatient units at a private psychiatric hospital.
PARTICIPANTS: Fifty-three first-episode patients, 27 with schizophrenia and 26 with affective (mainly manic) psychosis, and 29 control subjects.
MAIN OUTCOME MEASURES: Using high-spatial resolution magnetic resonance imaging, the gray matter volumes of 2 olfactocentric paralimbic regions of interest, the insular cortex and the temporal pole, were evaluated.
RESULTS: A bilateral volume reduction in insular cortex gray matter was specific to first-episode patients with schizophrenia. In contrast, both first-episode psychosis groups showed a volume reduction in left temporal pole gray matter and an absence of normal left-greater-than-right asymmetry. Region of interest correlations showed that only patients with schizophrenia lacked a positive correlation between left temporal pole and left anterior amygdala-hippocampal complex gray matter volumes, whereas both psychosis groups were similar in lacking normal positive correlations between left temporal pole and left anterior superior temporal gyrus gray matter volumes.
CONCLUSIONS: These partially different and partially similar patterns of structural abnormalities in olfactocentric paralimbic regions and their associated abnormalities in other temporolimbic regions may be important factors in the differential and common manifestations of the 2 psychoses.
In this study the self-diffusion of different species in highly concentrated water-in-oil emulsions was investigated by means of the NMR diffusometry approach. The emulsions contained 96% aqueous solutions of salt or other additives; heptane was used as the oil phase. The surfactants, used to stabilize the emulsion, were soybean phosphatidylcholine and C(12)EO(4). The water drops were about 1.5 microm in diameter according to diffusion measurements performed on water. Diffusion of tetramethyl ammonium ions and glucose between the emulsion droplets was found to be negligible on the relevant time-scale (<1 s). On the contrary, acetic acid/acetate ions diffused between the droplets and had exchange times which were a function of pH.
The fusiform gyrus is important for face and object recognition, is abnormal in schizophrenia, but has not been studied in schizotypal personality disorder (SPD). Thin-slice MR images showed no differences, either in right, left or total fusiform gyri volumes, between subjects with SPD (N=21) and normal controls (N=19). However, there was a correlation between severity of illusions and magical thinking suffered by the SPD subjects and smaller right fusiform gyrus volumes. This suggests that future studies may be useful in determining the functional competence of this gyrus in SPD.
BACKGROUND: The Heschl gyrus and planum temporale have crucial roles in auditory perception and language processing. Our previous investigation using magnetic resonance imaging (MRI) indicated smaller gray matter volumes bilaterally in the Heschl gyrus and in left planum temporale in patients with first-episode schizophrenia but not in patients with first-episode affective psychosis. We sought to determine whether there are progressive decreases in anatomically defined MRI gray matter volumes of the Heschl gyrus and planum temporale in patients with first-episode schizophrenia and also in patients with first-episode affective psychosis.
METHODS: At a private psychiatric hospital, we conducted a prospective high spatial resolution MRI study that included initial scans of 28 patients at their first hospitalization (13 with schizophrenia and 15 with affective psychosis, 13 of whom had a manic psychosis) and 22 healthy control subjects. Follow-up scans occurred, on average, 1.5 years after the initial scan.
RESULTS: Patients with first-episode schizophrenia showed significant decreases in gray matter volume over time in the left Heschl gyrus (6.9%) and left planum temporale (7.2%) compared with patients with first-episode affective psychosis or control subjects.
CONCLUSIONS: These findings demonstrate a left-biased progressive volume reduction in the Heschl gyrus and planum temporale gray matter in patients with first-episode schizophrenia in contrast to patients with first-episode affective psychosis and control subjects. Schizophrenia but not affective psychosis seems to be characterized by a postonset progression of neocortical gray matter volume loss in the left superior temporal gyrus and thus may not be developmentally fixed.
Schizophrenia has long been associated with abnormal patterns of arousal that are thought to reflect disturbances in the reticular-activating system of the brain. Psychophysiological investigations of sensory responsivity have repeatedly demonstrated reduced reactivity and habituation to moderately intense stimuli in patients with schizophrenia. While not traditionally used as a measure of physiological arousal, the startle reflex represents an alternative method for studying reactivity and habituation in schizophrenia. This study examined eye blink responsivity to a repeatedly presented intense acoustic startle probe in men with chronic schizophrenia and healthy normal controls. Subjects' personality profiles were also measured, as increased reactivity and arousal have been traditionally implicated as a physiological component to the personality trait of neuroticism. Results indicated that schizophrenic subjects did demonstrate significantly reduced rates of habituation to the acoustic startle probe and higher scores on measures of neuroticism in comparison to normal controls. However, no correlation between habituation rate and neuroticism emerged. These studies replicate previous findings of habituation in schizophrenia and provide further evidence for sensory reactivity disturbances in schizophrenia. The relationship of these findings to cognitive disturbances in schizophrenia is considered and directions for future research are discussed.
OBJECTIVE: An abnormal superior temporal gyrus has figured prominently in schizophrenia research, and left superior temporal gyrus volume has been shown to be smaller in male subjects with schizotypal personality disorder. This is the first structural magnetic resonance imaging study to examine a group of female subjects with schizotypal personality disorder.
METHOD: The superior temporal gyrus was drawn on coronal images acquired from female subjects recruited from the community (schizotypal personality disorder group: N=21, comparison group: N=29).
RESULTS: There were no gray matter volume differences in the left or right superior temporal gyrus between the subjects with schizotypal personality disorder and the comparison subjects. Within the schizotypal personality disorder group, however, there was an interaction between hemisphere and family history of mental illness. Moreover, subjects with schizotypal personality disorder did demonstrate formal thought disorder and a negative correlation between left superior temporal gyrus volume and odd speech.
CONCLUSIONS: This study of female subjects with schizotypal personality disorder showed no superior temporal gyrus volume differences, but preliminary findings indicate that among female subjects with schizotypal personality disorder, there is a left-right difference in those who have a family history of mental illness relative to those who do not. These data also suggest an association between abnormal speech and left superior temporal gyrus volume, a finding similar to that found in schizophrenia. Results from this study thus clearly reinforce the importance of studying female subjects separately.
RATIONALE AND OBJECTIVES: The accuracy of diagnostic test and imaging segmentation is important in clinical practice because it has a direct impact on therapeutic planning. Statistical validations of classification accuracy was conducted based on parametric receiver operating characteristic analysis, illustrated on three radiologic examples,
MATERIALS AND METHODS: Two parametric models were developed for diagnostic or imaging data. Example 1: A semi-automated fractional segmentation algorithm was applied to magnetic resonance imaging of nine cases of brain tumors. The tumor and background pixel data were assumed to have bi-beta distributions. Fractional segmentation was validated against an estimated composite pixel-wise gold standard based on multi-reader manual segmentations. Example 2: The predictive value of 100 cases of spiral computed tomography of ureteral stone sizes, distributed as bi-normal after a non-linear transformation, under two treatment options received. Example 3: One hundred eighty cases had prostate-specific antigen levels measured in a prospective clinical trial. Radical prostatectomy was performed in all to provide a binary gold standard of local and advanced cancer stages. Prostate-specific antigen level was transformed and modeled by bi-normal distributions. In all examples, areas under the receiver operating characteristic curves were computed. RESULTS. The areas under the receiver operating characteristic curves were: Example 1: Fractional segmentation of magnetic resonance imaging of brain tumors: meningiomas (0.924-0.984); astrocytomas (0.786-0.986); and other low-grade gliomas (0.896-0.983). Example 3: Ureteral stone size for treatment planning (0.813). Example 2: Prostate-specific antigen for staging prostate cancer (0.768).
CONCLUSION: All clinical examples yielded fair to excellent accuracy. The validation metric area under the receiver operating characteristic curves may be generalized to evaluating the performances of several continuous classifiers related to imaging.
OBJECTIVE: To investigate the geometry of the glenohumeral joint using three-dimensional (3D) models; define landmarks, planes, angles and regions of interest; and analyze the exact morphology of the scapula.
MATERIALS AND METHODS: We reconstructed 3D scapula models based on computed tomography (CT) data sets of 12 healthy controls. Three-dimensional models were reconstructed using the 3D Slicer2 (Surgical Planning Lab, Boston, MA), which provides interactive measurement. The 3D model and measuring tools can be freely shifted and rotated in all planes.
RESULTS: The average length of the scapulas was 209.58 +/- 26.72 mm (left) and 223.68 +/- 47.74 mm (right); width was 124.03 +/- 13.28 mm (left) and 141.44 +/- 27.78 mm (right); and volume was 121.38 +/- 12.02 ml (left) and 130.24 +/- 20.86 ml (right). The glenoid dimensions were 34.34 +/- 5.62 mm (left) and 36.44 +/- 7.36 mm (right) (anteroposterior); and 49.16 +/- 7.68 mm (left), 51.46 +/- 10.07 mm (right) (superoinferior). For all average values, scapulas from male controls were significantly larger than those from females, and right sides were larger than left sides (p < 0.05). The glenoid version was nearly the same for male/female and left/right (left = 9.02 +/- 3.89 degrees retroversion; right = 8.26 +/- 3.72 degrees retroversion) (p > or = 0.05).
CONCLUSION: The 3D measurement of scapula morphology compared with geometry of the glenohumeral joint leads to a more precise planning of shoulder surgery. As new shoulder prostheses are intended to reconstruct the normal anatomy as closely as possible, such exact 3D measurements may be used for optimization.
Evidence suggests that a disruption in limbic system network integrity and, in particular, the cingulate gyrus (CG), may play a role in the pathophysiology of schizophrenia; however, the cingulum bundle (CB), the white matter tract furnishing both input and output to CG, and the most prominent white matter fiber tract in the limbic system, has not been evaluated in schizophrenia using the new technology of diffusion tensor imaging (DTI). We used line scan DTI to evaluate diffusion in the CB in 16 male schizophrenia patients and 18 male control subjects, group-matched for age, parental socioeconomic status, and handedness. We acquired 4-mm-thick coronal slices through the entire brain. Maps of fractional anisotropy (FA) were generated to quantify diffusion within the left and right CB on eight slices that included the central portion of the CB. Results showed group differences, bilaterally, in area and mean FA for CB, where patients showed smaller area and less anisotropy than controls. For patients, decreased left CB correlated significantly with attention and working memory measures as assessed by the Wisconsin Card Sorting Test. These data provide strong evidence for CB disruptions in schizophrenia, which may be related to disease-related attention and working memory abnormalities.