Biomedical subjects

R E Gur

Publications and source records attributed to R E Gur.

At least 37 records · Page 2Linked to original sources

PubMed2000

Working memory constrains abstraction in schizophrenia.

BACKGROUND: Abstraction has long been considered an area of differential cognitive deficit in schizophrenia, primarily because of patients' poor performance on the Wisconsin Card Sorting Test (WCST). Yet, the complexity and multidimensional nature of the WCST increases the likelihood that several different cognitive processes, perhaps mediated by different neural systems, are being tapped. METHODS: In the current study, the Abstraction and Working Memory (AIM) task was designed to disentangle abstraction and working memory so that the effects of each cognitive domain could be independently analyzed. The AIM task and a battery of neuropsychological tests were administered to 62 patients with schizophrenia and 62 matched healthy volunteers. RESULTS: Whereas patients with schizophrenia demonstrated deficits in simple abstraction, they were disproportionately impaired with the addition of a minimal memory requirement. CONCLUSIONS: Group differences on WCST performance appear to be attributable to patients' inability to maintain information over a short delay, before that information is used for more complex cognitive operations.

Adolescent↗

PubMed2000

Reduced dorsal and orbital prefrontal gray matter volumes in schizophrenia.

BACKGROUND: Converging neuroanatomic, neurophysiological, and neurobehavioral evidence implicate prefrontal subregions in schizophrenia. Neuroanatomic studies with magnetic resonance (MR) imaging enable regional volume parcellation. Inconsistent reports may relate to variable methods and small samples. We attempted to resolve volume differences within sectors of the prefrontal lobe in a large sample, relating volumes to clinical and neurocognitive features. METHODS: Magnetic resonance imaging was performed in 70 patients with schizophrenia (40 men and 30 women; 29 neuroleptic naive and 41 previously treated) and 81 healthy controls (34 men and 47 women). Gray and white matter volumes of the dorsolateral, dorsomedial, orbitolateral, and orbitomedial prefrontal cortex were quantified. Symptoms, functioning, and neurocognition were assessed concurrently. RESULTS: Reduced prefrontal gray matter volume was observed in patients. The reduction was evident for the dorsolateral area in men (9%) and women (11%), for the dorsomedial area only in men (9%), and for orbital regions only in women (23% and 10% for lateral and medial, respectively). The reduction of orbital volume in women was associated with poorer premorbid functioning, more severe negative symptoms, and depression. Volume of dorsal cortex was positively associated with better performance on abstraction and attention tasks across all groups. CONCLUSIONS: Schizophrenia is associated with reduced gray matter volume in prefrontal cortex, which affects men and women in the dorsolateral sector. The effects are moderated by sex for dorsomedial and orbital regions and are related to symptom severity and cognitive function. This is not a by-product of treatment, since the differences are evident in neuroleptic-naive patients.

Adult↗

PubMed2000

Temporolimbic volume reductions in schizophrenia.

BACKGROUND: Neuroanatomic studies of schizophrenia have reported temporolimbic abnormalities. Most magnetic resonance imaging studies have evaluated small samples of primarily men with chronic schizophrenia. Our goal was to evaluate sex differences in segmented temporal lobe subregions with reliable parcellation methods, relating volume with clinical and neurocognitive parameters. METHODS: Magnetic resonance imaging was performed in 100 patients with schizophrenia (58 men, 42 women; 39 neuroleptic naive, 61 previously treated) and 110 healthy controls (51 men, 59 women). Gray and white matter volumes of temporolimbic (hippocampus and amygdala) and neocortical regions (superior temporal gyrus and temporal pole) were examined. Symptoms, functioning, and neurocognition were assessed concurrently. RESULTS: Hippocampal gray matter volume was reduced in men (7%) and women (8.5%) with schizophrenia. In the amygdala, however, decreased volume was evident for men (8%) whereas women (10.5%) had increased volume. Magnetic resonance imaging of the temporal pole showed decreased gray matter in men (10%) and women (8.5%). For the superior temporal gyrus, the decrease exceeded that of whole-brain only in men (11.5%). Volumes were largely uncorrelated with clinical measures, but higher hippocampal volumes were associated with better memory performance for all groups. Cortical volumes were associated with better memory performance in healthy women. CONCLUSIONS: Schizophrenia is associated with reduced gray matter volume in temporolimbic structures. In men, reduction was manifested in all regions, whereas women showed decreased hippocampal volumes but increased amygdala volumes. The abnormalities are evident in patients with first-episode schizophrenia and correlate more strongly with cognitive performance than with symptom severity.

Adult↗

PubMed2000

An fMRI study of sex differences in regional activation to a verbal and a spatial task.

Sex differences in cognitive performance have been documented, women performing better on some phonological tasks and men on spatial tasks. An earlier fMRI study suggested sex differences in distributed brain activation during phonological processing, with bilateral activation seen in women while men showed primarily left-lateralized activation. This blood oxygen level-dependent fMRI study examined sex differences (14 men, 13 women) in activation for a spatial task (judgment of line orientation) compared to a verbal-reasoning task (analogies) that does not typically show sex differences. Task difficulty was manipulated. Hypothesized ROI-based analysis documented the expected left-lateralized changes for the verbal task in the inferior parietal and planum temporal regions in both men and women, but only men showed right-lateralized increase for the spatial task in these regions. Image-based analysis revealed a distributed network of cortical regions activated by the tasks, which consisted of the lateral frontal, medial frontal, mid-temporal, occipitoparietal, and occipital regions. The activation was more left lateralized for the verbal and more right for the spatial tasks, but men also showed some left activation for the spatial task, which was not seen in women. Increased task difficulty produced more distributed activation for the verbal and more circumscribed activation for the spatial task. The results suggest that failure to activate the appropriate hemisphere in regions directly involved in task performance may explain certain sex differences in performance. They also extend, for a spatial task, the principle that bilateral activation in a distributed cognitive system underlies sex differences in performance.

Brain↗

PubMed2000

Hemispheric activation of anterior and inferior prefrontal cortex during verbal encoding and recognition: a PET study of healthy volunteers.

Evidence of bilateral prefrontal activation during memory encoding and retrieval has increased attention given to anatomical subdivisions within the prefrontal cortex. The current study examined anterior and inferior aspects of the prefrontal cortex to determine their degree of functional and hemispheric overlap during encoding and recognition. Cerebral blood flow of 25 healthy volunteers was measured using PET (15)O-water methods during four conditions: resting baseline, sequential finger movement, word encoding, and word recognition. Resting and motor images were averaged to provide a single reference that was subtracted from encoding and recognition using statistical parametric mapping (SPM96). Memory conditions were also subtracted from each other to identify differences in regional activity. Subjects performed well (86% correct) and had a slightly conservative response bias. Baseline subtraction from encoding revealed focal activation of left inferior prefrontal cortex (area 45) without significant contralateral activation. Recognition minus baseline subtraction produced a focal right anterior prefrontal activation (areas 9 and 10) that was not present in the left hemisphere. Bilateral effects were seen in area 45 during recognition. Subtraction of memory tasks from each other did not reveal any areas of greater activity during encoding. However, the recognition task produced greater activation in right area 9 extending into the anterior cingulate. Greater activity during recognition was also observed in left insula and bilateral visual integration areas. These results are discussed in relation to the prevailing model of prefrontal hemispheric asymmetry during episodic memory.

Adult↗

PubMed2000

Sex differences in brain-behavior relationships between verbal episodic memory and resting regional cerebral blood flow.

Women have better verbal memory, and higher rates of resting regional cerebral blood flow (rCBF). This study examined whether there are also sex differences in the relationship between verbal episodic memory and resting rCBF. Twenty eight healthy right-handed volunteers (14 male, 14 female) underwent a neuropsychological evaluation and a Positron Emission Tomography (PET) (15)O-water study. Immediate and delayed recall was measured on the logical memory subtest of the Wechsler Memory Scale - Revised (WMS-R), and on the California Verbal Learning Test (CVLT). Resting rCBF (ml/100 g/min) was calculated for four frontal, four temporal, and four limbic regions of interest (ROIs). Women had better immediate recall on both WMS-R and CVLT tasks. Sex differences in rCBF were found for temporal lobe regions. Women had greater bilateral blood flow in a mid-temporal brain region. There were also sex differences in rCBF correlations with performance. Women produced positive correlations with rCBF laterality in the temporal pole. Greater relative CBF in the left temporal pole was associated with better WMS-R immediate and delayed recall in women only. These results suggest that trait differences in temporal pole brain-behavior relationships may relate to sex differences in verbal episodic memory.

Adolescent↗

PubMed2000

Regional cerebral glucose metabolism in healthy volunteers determined by fluordeoxyglucose positron emission tomography: appearance and variance in the transaxial, coronal, and sagittal planes.

PURPOSE: In this study, the contribution of the transaxial, coronal, and sagittal planes in evaluations of regional cerebral glucose metabolism was investigated in healthy volunteers as determined by fluorine-18-labeled 2-deoxy-2-fluoro-D-glucose (FDG) and high-resolution positron emission tomography (PET). METHODS: One hundred twenty-seven healthy right-handed volunteers were injected with 4.2 MBq/kg (0.11 mCi) body weight FDG and imaged in a PENN PET H 240 scanner. Images were corrected for scatter and random coincidences and reconstructed in all three planes into 6- to 8-mm-thick slices. The reconstructed images were corrected for attenuation using the Chang algorithm. The transverse, coronal, and sagittal images were read independently of each other using a qualitative scale in which 1 = equal to, 2 = mildly, 3 = moderately, and 4 = markedly less than the area with the highest glucose metabolism in the respective plane. RESULTS: The areas with the highest glucose metabolisms were the posterior cingulate gyri with mean scores of 1.1 to 1.2, thalami (1.2 to 1.3), basal ganglia (1.5 to 1.9), and visual cortex (1.6). The lowest values were found in the occipital cortex (2.7 to 2.8) and the cerebellum (2.3 to 2.4). Whereas reliable analysis of the mesial temporal aspects was not feasible in the sagittal plane, the anterior poles of the temporal and frontal lobes could not be evaluated in the coronal or the inferior temporal areas in the transaxial slices. In all three planes, regional glucose metabolism was less in the lateral temporal areas on the left than on the right (P < 0.001). The consistency of readings as measured in terms of coefficients of variation was greatest in the coronal plane for the caudates and posterior cingulate gyri, in the transaxial plane for the lateral temporal regions, and in the sagittal plane for the visual cortex. Age-dependent decreases in regional glucose metabolism in the inferior and lateral frontal regions and the parietal lobes were found in all three planes. CONCLUSIONS: All three projection planes must be used for a comprehensive qualitative evaluation of the regional glucose metabolism of the brain.

Adult↗

PubMed2000

Reduced olfactory bulb volume in patients with schizophrenia.

OBJECTIVE: The authors' goal in this study was to compare the size of olfactory bulbs of patients with schizophrenia and those of healthy subjects. METHOD: Magnetic resonance imaging scans of olfactory bulbs were obtained from 26 patients with schizophrenia and 22 healthy comparison subjects. A reliable region of interest procedure was used to measure olfactory bulb volume. RESULTS: Patients exhibited 23% smaller bilateral bulb volume than comparison subjects, independent of acute clinical, demographic, or treatment measures. Bulb volume correlated with odor detection sensitivity in healthy subjects but not in patients with schizophrenia. CONCLUSIONS: Patients with schizophrenia exhibit structural olfactory deficits as well as functional olfactory deficits. The olfactory system may be a model system in which to study the neurobiology of the disorder.

Adult↗

PubMed2000

The relation between tendency for psychopathology and reduced frontal brain volume in healthy people.

OBJECTIVE: We hypothesized that tendency toward psychopathology is associated with lower frontotemporal volumes. BACKGROUND: Although there is considerable evidence for structural abnormalities in patients with major psychiatric disorders and increased recognition that neural substrates may underlie individual differences in personality, there have been no studies in healthy people attempting to relate personality to volumetric measures of brain structure. METHOD: We used magnetic resonance imaging with an advanced method for automated segmentation of cranial compartments to gray matter, white matter, and cerebrospinal fluid. We examined the relation between frontal and temporal lobe volumes and Minnesota Multiphasic Personality Inventory measures of tendency toward psychopathology in 59 healthy individuals. RESULTS: As hypothesized, higher scores on the clinical scales were associated with lower average frontal lobe volume. When the sample was divided according to sex, however, these correlations were significant in men (n = 29) but not in women (n = 30). The highest correlation was observed between lower frontal white matter volume in men and high schizophrenia scale score (r[27] = -0.59, p <0.001). CONCLUSIONS: The findings suggest that personality dimensions in healthy people can be linked to neural substrates, which can potentially serve as endophenotypic markers of disposition to psychopathology. The sexually dimorphic effects are consistent with gender-related differences in the clinical manifestations of psychiatric disorders and may suggest sex hormone modulation of the psychopathologic processes.

Adult↗

PubMed1999

Sex differences in brain gray and white matter in healthy young adults: correlations with cognitive performance.

Sex-related differences in behavior are extensive, but their neuroanatomic substrate is unclear. Indirect perfusion data have suggested a higher percentage of gray matter (GM) in left hemisphere cortex and in women, but differences in volumes of the major cranial compartments have not been examined for the entire brain in association with cognitive performance. We used volumetric segmentation of dual echo (proton density and T2-weighted) magnetic resonance imaging (MRI) scans in healthy volunteers (40 men, 40 women) age 18-45. Supertentorial volume was segmented into GM, white matter (WM), and CSF. We confirmed that women have a higher percentage of GM, whereas men have a higher percentage of WM and of CSF. These differences sustained a correction for total intracranial volume. In men the slope of the relation between cranial volume and GM paralleled that for WM, whereas in women the increase in WM as a function of cranial volume was at a lower rate. In men the percentage of GM was higher in the left hemisphere, the percentage of WM was symmetric, and the percentage of CSF was higher in the right. Women showed no asymmetries. Both GM and WM volumes correlated moderately with global, verbal, and spatial performance across groups. However, the regression of cognitive performance and WM volume was significantly steeper in women. Because GM consists of the somatodendritic tissue of neurons whereas WM comprises myelinated connecting axons, the higher percentage of GM makes more tissue available for computation relative to transfer across distant regions. This could compensate for smaller intracranial space in women. Sex difference in the percentage and asymmetry of the principal cranial tissue volumes may contribute to differences in cognitive functioning.

Adolescent↗

PubMed1999

Reduced gray matter volume in schizophrenia.

BACKGROUND: There is emerging evidence that gray matter (GM) is reduced in patients with schizophrenia. Information on the extent of global differences in the 3 principal supertentorial compartments is necessary for interpretation of regional effects. The relation of GM reduction to clinical status and neurocognition also requires examination. METHODS: Magnetic resonance imaging, neurocognitive measures, and clinical assessment of symptoms and functioning were obtained for 130 patients (51 neuroleptic naive, 79 previously treated) and 130 healthy controls (75 men, 55 women in each group). RESULTS: Overall GM volume was reduced in patients compared with controls. This was evident in men (6% reduction) and women (2% reduction) and was already evident at the first presentation of neuroleptic-naive patients. The reduction sustained correction for age and total intracranial volume. Compartmental volumes did not correlate with the severity of positive (r, -0.08 to 0.23) or negative (r, -0.01 to -0.07) symptoms, but GM volume was associated with better premorbid functioning in women (r, 0.36-0.51). Small but significant correlations (r, 0.19-0.44) were observed between GM volume and performance in 6 neurocognitive domains. These correlations varied by diagnosis, most higher in patients, and were moderated by sex. CONCLUSIONS: Gray matter volume reduction in schizophrenia is already evident in men and women at first presentation. While this reduction is not correlated with symptom severity, it is associated with cognitive performance. Since GM development accelerates in the later part of gestation, while white matter growth is primarily postnatal, the results may support the hypothesis that neurodevelopmental processes relate to GM deficit.

Adult↗

PubMed1999

Proton magnetic resonance spectroscopy in the frontal and temporal lobes of neuroleptic naive patients with schizophrenia.

Studies with proton magnetic resonance spectroscopy (MRS) have reported abnormalities in N-acetyl-aspartate (NAA), amino acids (AA) and choline (Cho) to creatine (Cr) ratios associated with schizophrenia. We report data on the three ratios in a sample of 18 neuroleptic naive patients with first-episode schizophrenia (eight studied in the dorsolateral prefrontal and 10 in the midtemporal lobe) and 24 healthy controls (14 studied in prefrontal and 10 in midtemporal lobes). Frontal lobe proton spectra were acquired with the stimulated-echo acquisition mode (STEAM) pulse sequence (echo time 21 ms, repetition time 2 s). Temporal lobe proton spectra were acquired with the point-resolved spectroscopy (PRESS) pulse sequence (echo time 16-21 ms, repetition time 2 s). Upon comparison with normal controls, NAA/Cr ratios were reduced in patients both for the frontal and the temporal lobe. By contrast, Cho/Cr ratios were slightly elevated in frontal and reduced in temporal lobes; whereas, AA/Cr ratios were normal in frontal and markedly increased in the temporal lobe. The reduced NAA/Cr ratios suggest lower neuronal viability in patients and is consistent with findings of reduced brain volume in both frontal and temporal regions.

Adult↗

PubMed1999

Olfactory dysfunction in schizophrenia: a qualitative and quantitative review.

Olfactory dysfunction in patients with schizophrenia has been a topic of increasing interest, with deficits in odor identification, detection threshold sensitivity, discrimination, and memory being reported. Despite increasing knowledge, controversy has existed about possible differential deficits among olfactory tests as well as the influences of gender, smoking, and medication status on olfactory measures. To help elucidate some of this controversy, we conducted a qualitative and quantitative (meta-analytic) review of the English language literature on olfaction in schizophrenia. Moderator variables such as gender, medication status, and smoking history were also examined. Results indicated that substantial olfactory deficits, across all domains, are observed in patients with schizophrenia. No differential deficits were observed across domains of odor identification, detection threshold sensitivity, discrimination, and memory. The influences of gender, medication status, and smoking on effect sizes were not significant across studies. This supports the hypothesis of primary dysfunction in the olfactory system that is regulated by brain regions where structural and functional abnormalities have also been reported in neuroimaging studies.

Humans↗

PubMed1999

Laterality in functional brain imaging studies of schizophrenia.

Brain laterality in schizophrenia has been examined through the application of functional neuroimaging methods. These methods have included the 133Xenon technique for measuring cerebral blood flow (CBF); positron emission tomography for assessing rates of glucose metabolism, CBF, and neuroreceptor functioning; single photon emission computerized tomography for studying CBF and neuroreceptors; and functional magnetic resonance imaging for measuring changes attributable to CBF. This article highlights the application of this technology in schizophrenia research, emphasizing more recent studies that have evaluated hemispheric differences. There is evidence for lateralized abnormalities in some studies that have examined this dimension. In general, the results implicate abnormalities in left hemispheric activity. Recent advances in basic and clinical neuroscience provide an opportunity for focused application of functional imaging in neurobiological studies of schizophrenia.

Brain↗

PubMed1999

Is Schizophrenia a lateralized brain disorder? Editor's introduction.

Lateralization of brain function was established on the basis of clinical-pathological correlations over a century ago. In the past two decades, this line of research has attempted to link the complex behaviors evident in schizophrenia to the failure to develop and maintain a normal pattern of hemispheric activity. This issue of Schizophrenia Bulletin reviews and presents data from multiple perspectives of methods applied to the study of laterality in schizophrenia. Brain disorders affecting systems that modulate complex behavior are commonly related to laterality. Therefore, this dimension of brain function merits further investigation in schizophrenia.

Cerebral Cortex↗

PubMed1999

Neuropsychological laterality indices of schizophrenia: interactions with gender.

Neurobehavioral laterality indices were examined across motor, sensory, language versus spatial, and verbal memory versus spatial memory domains for 75 patients with schizophrenia (45 men, 30 women) and 75 demographically matched healthy controls. Patients were impaired across tasks, and laterality results varied by domain. There was no evidence for diagnosis by hemisphere interactions in motor, sensory, or memory tasks. However, patients were more impaired in language than in spatial domains, which suggests relatively greater left hemisphere dysfunction. This finding was mediated by the sex of the participant. While patients as a group showed greater language than spatial impairment, male patients showed expected superiority in spatial relative to language performance, whereas female patients performed the same on both functions. These results underscore the importance of examining sex differences in laterality effects. The findings also demonstrate that, although the left hemisphere model of schizophrenia may be partially supported by data on higher cognitive functions, this support does not extend to more basic motor and sensory domains.

Adult↗

PubMed1999

Depression in temporal lobe epilepsy before epilepsy surgery.

PURPOSE: This study examined the association of depression with laterality of epilepsy surgery in patients with temporal lobe epilepsy before standard lobectomy. METHODS: Forty-nine patients presented for EEG telemetry for localization of epilepsy and eventual temporal lobectomy. Patients underwent routine neuropsychiatric evaluation blinded for epileptic focus, including ratings on depression. Patients were grouped according to right (n = 25, M = 10/F = 15) and left (n = 24, M = 13/F = 11) temporal lobectomy. Analysis of variance included side of surgery as grouping variable and sex, general depressive, cognitive depressive, and vegetative depressive symptoms as dependent variables. Chi2 analyses included categoric variables of sex, handedness, education, neuropathologic findings, and current affective disorders. t Tests were performed on variables of age, epilepsy duration, and cognitive function. RESULTS: Right and left temporal epilepsy groups did not differ with regard to sex, handedness, age, duration of epilepsy, education, cognitive function, and neuropathology. Patients with right temporal epilepsy rated higher on general, cognitive. and vegetative depression scores. Women scored higher on general, cognitive, and vegetative depression scores. Current affective disorders were more common in the right temporal epilepsy group. CONCLUSIONS: Depression ratings and diagnoses were more prominent in patients with right temporal lobe epilepsy and in women in particular. The strength of this laterality finding lies in the selection of patients, as all underwent epilepsy surgery. The finding on gender difference partly reflects the higher incidence of depression in women and needs further exploration. The laterality finding contrasts with recent findings in epilepsy, stroke, and trauma that associate depression with left hemispheric lesions. However, our results are consistent with findings in electrically hyperactive lesions such as gelastic and dacrystic epilepsy.

Adolescent↗

PubMed1998

Premorbid educational attainment in schizophrenia: association with symptoms, functioning, and neurobehavioral measures.

BACKGROUND: The purpose of this study was to examine the association of educational attainment with phenomenology and neurobehavioral measures assessing brain structure and function in schizophrenia. METHODS: One hundred sixty-two patients with schizophrenia were divided into two groups on the basis of educational attainment: > or = 13 years of education was the cutoff between the high and low groups. The two education groups were compared on symptomatology, functioning, and subsamples on neuropsychological profile, brain volume by magnetic resonance imaging, and brain metabolism by fluorodeoxyglucose positron-emission tomography. RESULTS: The patients with more education had lower levels of psychotic symptomatology than their counterparts with less education. This was most evident for affective flattening, alogia, avolition, and bizarre behavior. The higher education group also had better ratings on premorbid adjustment, and the engagement and vocational factors of the Quality of Life Scale. Patients in the high education group also performed better on the neuropsychological battery. There were no brain volume differences or differences in brain metabolism between the two education groups. CONCLUSIONS: Education is an important indicator of premorbid function and is related to the clinical presentation of schizophrenia.

Adolescent↗