Biomedical subjects

R C Gur

Publications and source records attributed to R C Gur.

At least 37 records · Page 2Linked to original sources

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

Association between age-related decline in brain dopamine activity and impairment in frontal and cingulate metabolism.

OBJECTIVE: Despite the well-documented loss of brain dopamine activity with age, little is known about its functional consequences in healthy individuals. This study investigates the relationship between measures of brain dopamine D(2) receptors (molecules that transmit dopamine signals) and regional brain glucose metabolism (a marker of brain function) in healthy individuals. METHOD: Thirty-seven healthy volunteers aged 24-86 years underwent positron emission tomography scans after injection of [(11)C]raclopride to assess dopamine D(2) receptors and [(18)]fluorodeoxyglucose to assess regional brain glucose metabolism. Two methods used to assess the correlations between metabolism and dopamine D(2) receptors-pixel-by-pixel correlations and correlations in preselected regions of interest-were then compared. RESULTS: D(2) receptors as well as frontal and cingulate metabolism declined with age. Regardless of the method used, significant correlations between metabolism and D(2) receptors were found in the frontal cortex (Brodmann's areas 6, 7, 8, 9, 10, 11, 44, 45, 47), anterior cingulate gyrus (areas 24, 32), temporal cortex (area 21), and caudate. These correlations remained significant after removing age effects (partial correlation). CONCLUSIONS: These results provide the first link between age-related declines in brain dopamine activity and frontal and cingulate metabolism, which supports the need to investigate the therapeutic utility of interventions that enhance dopamine function in the elderly. The fact that correlations remained significant after removing age effects suggests that dopamine may influence frontal, cingulate, and temporal metabolism regardless of age.

Adult↗

PubMed2000

Marchiafava-Bignami disease: literature review and case report.

OBJECTIVE: We postulated that disruption of callosal pathways as occurs in Marchiafava-Bignami disease (MBD) is associated with marked impairment in brain functioning as measured by cognitive assessment and neuroimaging. BACKGROUND: MBD is considered to be a rare and severe complication of chronic alcoholism. It is characterized by necrosis and subsequent atrophy of the corpus callosum, which is the major brain structure connecting corresponding areas of both hemispheres. METHODS: We review the existing literature on MBD with respect to conceptualization, theories of pathogenesis, forms of the disease, and neuroimaging and neuropsychological findings. We then present the case of a middle-aged man with MBD who underwent extensive clinical, neuropsychological, and neuroimaging studies. RESULTS: Neuropsychological evaluation revealed a pattern of severe global dementia. Magnetic resonance imaging showed moderate atrophy of anterior callosal regions and severe atrophy of posterior callosal regions in the setting of cortical and subcortical atrophy. Resting metabolism positron emission tomography revealed decreased glucose metabolism most pronounced in subcortical and mesial frontal regions. The differential diagnosis, function of the corpus callosum, and potential limitations of our case study are discussed. CONCLUSIONS: On account of the history, clinical presentation, and results of magnetic resonance imaging of the brain, we diagnosed our patient with chronic MBD.

Alcohol-Related Disorders↗

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

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

A comparative volumetric analysis of the prefrontal cortex in human and baboon MRI.

The proportion of prefrontal cortex in humans was compared to the proportion of prefrontal cortex in baboons (Papio anubis). Prefrontal cortex, dorsal prefrontal, orbital prefrontal cortex and total brain volumes were determined from magnetic resonance images of 20 healthy adult human females and 5 adult female baboons. Results showed that the proportion of prefrontal cortex volume relative to total brain volume in humans was significantly larger in humans than in baboons. The percentage of prefrontal cortex relative to total brain volume was 12.51 for humans and 10.68 for baboons. Similarly, the proportion of both dorsal and orbital prefrontal cortex volumes is larger in human brains. Relative to total brain volume, the percentages of dorsal and orbital prefrontal cortex was 8.22% and 4.29% respectively in humans and 7.21% and 3.47% in baboons. A regression analysis showed that the human prefrontal cortex was larger than would be predicted for a baboon of equal total brain volume. These results suggest that increased prefrontal lobe volume could underlie some of the differences between human and hominoid primates. On the other hand, the small magnitude of the difference might underlie similarities between the species and should encourage a search for other structures that are disproportionately larger in humans.

Adult↗

PubMed1999

Effects of age on dopamine transporters in healthy humans.

UNLABELLED: 99mTc-TRODAT-1 is a new radiopharmaceutical that selectively binds the dopamine transporters. This study characterized the effects of aging on its regional cerebral distribution in healthy human volunteers. METHODS: The sample consisted of 27 men and 28 women with a mean age of 41.1 +/- 17.1 y (age range 18.7-73.8 y). Dynamic SPECT scans of the brain were obtained with a standardized acquisition and processing protocol on a triple-head camera. Mean counts per pixel were measured in multiple regions of interest within each basal ganglia. Regression analyses were used to relate the specific uptake values at 3-4 h after administration to age. Both linear and nonlinear models of aging were tested. RESULTS: The relative concentration of radioactivity in most subregions of the basal ganglia decreased significantly with age (all P values < 0.0001). Nonlinear models of aging fit the data significantly better than a straight line. The rate of decline was significantly faster in young adults than in older volunteers (P < 0.001). The break-point age at which the rate of change slowed down and became more stable was 36 y old for the whole striatum and ranged from 32 to 44 y old depending on subregion. CONCLUSION: The effects of aging on central nervous system dopamine transporters do not appear to be linear. Most effects seem to occur during young adulthood before people reach their 40s. The distribution then appears to remain relatively stable until late in life. The findings suggest that the adult life cycle is better characterized as a series of phases than as a continuum.

Adult↗

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↗

PubMed1998

P50 abnormalities in schizophrenia: relationship to clinical and neuropsychological indices of attention.

While the P50 component (50-60-ms latency) of the auditory evoked potential has been reported as abnormal in schizophrenia, few studies have examined the relationship between this abnormality and clinical or neuropsychological measures. To examine these possible relationships, mid-latency auditory evoked potentials were recorded at the CZ recording site of 47 patients with schizophrenia in response to binaural clicks presented at three stimulus rates: 1, 5 and 10/sec. A sub-sample of patients were then divided into high- (n = 15) and low-P50 abnormality (n = 16) groups based on a median split of the P50 amplitude at a rate of 10/sec (a greater amplitude at this rate suggests a greater abnormality in recovery) of the entire sample. Only those patients with complete neuropsychological and clinical data and who were reasonably matched on demographic dimensions were included. A multivariate analysis of variance of 11 neuropsychological function profile scores showed a significant group x global score interaction (Hotelling t = 3.97, p < 0.005). The high-abnormality group had relatively greater deficits for attention profile scores than for the remaining neuropsychological measures. An analysis of global subscores for SAPS and SANS clinical measures revealed a significant difference only for the SANS attention subscale (p < 0.05). The high-abnormality group was rated as more severe on the attention measure. These convergent findings across both phenomenological and neuropsychological measures suggest that abnormalities in P50 recovery may be linked to deficits in attention processes in schizophrenia.

Adult↗

PubMed1998

Depression in schizophrenia: I. Association with neuropsychological deficits.

BACKGROUND: The presence of depression in schizophrenia has been well described with regard to stage and symptoms of illness; however, little is known about the possible etiology. METHODS: In an effort to advance the understanding of the neurobiology of depression in schizophrenia, we grouped patients with schizophrenia based on their ratings on the 21-item Hamilton Depression Rating Scale. There were 63 patients (35 men, 28 women) in the high (> or = 18) depression group and 81 patients (52 men, 29 women) in the low (< 18) depression group. The groups were compared in demographic, clinical, and eight neuropsychological domains. RESULTS: The two groups differed in age at onset of illness, severity of delusions, and performance in a single neuropsychological domain: attention. The specific component of impaired attention was vigilance, with poorest performance seen in women with higher depression scores. CONCLUSION: The presence of specific attentional impairment associated with depressive symptoms in schizophrenia is consistent with the hypothesis of frontal lobe dysfunction in depression, because these regions have been implicated in attentional processes.

Adult↗