Biomedical subjects

R C Gur

Publications and source records attributed to R C Gur.

At least 19 recordsLinked to original sources

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↗

PubMed1998

Depression in schizophrenia: II. MRI and PET findings.

BACKGROUND: Despite consistent descriptions of depressive symptoms in schizophrenia, little is known about their neurobiology. The purpose of this study was to examine the association of depression in schizophrenia with measures of brain anatomy and metabolism. METHODS: Seventy-nine patients were grouped according to their ratings on the Hamilton Depression Rating Scale (HDRS): > or = 18 was the cutoff between the "high" and "low" depression groups. All patients underwent clinical and magnetic resonance imaging (MRI) evaluation, and a subsample of 37 underwent 2-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) measurements of cerebral glucose metabolism. RESULTS: The high depression group had larger bilateral temporal lobe volumes and decreased laterality (left minus right of metabolism in the anterior cingulate). CONCLUSIONS: The neurobiology of depression in schizophrenia thus seems to share features with major depression due to other disease states.

Adult↗

PubMed1998

A follow-up magnetic resonance imaging study of schizophrenia. Relationship of neuroanatomical changes to clinical and neurobehavioral measures.

BACKGROUND: Cross-sectional neuroanatomical studies have reported abnormalities in schizophrenia that relate to disease variables. Longitudinal neuroimaging investigations that integrate anatomical, clinical, and neurobehavioral measures may help clarify the pathogenesis of schizophrenia. METHODS: Magnetic resonance brain imaging and neurobehavioral studies were conducted at baseline and after 30.63 +/- 12.92 months (mean +/- SD) in 40 patients with schizophrenia (23 men and 17 women) and 17 healthy controls (13 men and 4 women). The schizophrenia group included 20 first-episode and 20 previously treated subjects. Volumes of whole-brain, cerebrospinal fluid, and frontal and temporal lobes were measured. The severity of negative and positive symptoms was assessed, medications were monitored, and neurobehavioral functioning in 8 domains was evaluated. RESULTS: Both first-episode and previously treated patients had smaller brains and frontal and temporal lobes than controls at intake. Longitudinally, reduction in frontal lobe volume was found only in patients, whereas temporal lobe reduction was also seen in controls. The association between volume reduction and symptom changes differed between patient groups, but volume reduction was associated with decline in some neurobehavioral functions in both groups. Exploratory analysis suggested that neuroleptic dose is correlated with changes in all 3 domains. CONCLUSIONS: The existence of neuroanatomical and neurobehavioral abnormalities in patients with first-episode schizophrenia indicates that the brain dysfunction occurred before clinical presentation. However, there is also evidence of progression, in which anatomical changes may affect some clinical and neurobehavioral features of the illness in some patients.

Adult↗

PubMed1998

Parallel loss of presynaptic and postsynaptic dopamine markers in normal aging.

Aging of the human brain is associated with a decline in dopamine (DA) function, generally interpreted as reflecting DA cell loss. Positron emission tomography studies revealed that in healthy individuals, the age-related losses in DA transporters (presynaptic marker) were associated with losses in D2 receptors (postsynaptic marker) rather than with increases as is known to occur with DA cell loss. This association was specific for DA synaptic markers, because they were not correlated with striatal metabolism. Furthermore, the association was independent of age, suggesting that a common mechanism regulates the expression of receptors and transporters irrespective of age.

Adult↗

PubMed1998

Frontotemporal cerebral blood flow change during executive and declarative memory tasks in schizophrenia: a positron emission tomography study.

Schizophrenia affects prefrontal and temporal-limbic networks. These regions were examined by contrasting regional cerebral blood flow (rCBF) during executive (Wisconsin Card Sorting Test [WCST]), and declarative memory tasks (Paired Associate Recognition Test [PART]). The tasks, and a resting baseline, were administered to 15 patients with schizophrenia and 15 healthy controls during 10 min positron emission tomography 15O-water measures of rCBF. Patients were worse on both tasks. Controls activated inferior frontal, occipitotemporal, and temporal pole regions for both tasks. Similar results were obtained for controls matched to level of patient performance. Patients showed no activation of hypothesized regions during the WCST and activated the dorsolateral prefrontal cortex during the PART. On the PART, occipitotemporal activation correlated with better performance for controls only. Better WCST performance correlated with CBF increase in prefrontal regions for controls and in the parahippocampal gyrus for patients. Results suggest that schizophrenia may involve a breakdown in the integration of a frontotemporal network that is responsive to executive and declarative memory demands in healthy individuals.

Adult↗

PubMed1998

Association between decline in brain dopamine activity with age and cognitive and motor impairment in healthy individuals.

OBJECTIVE: Although it is documented that brain dopamine activity declines with age, the functional significance of this is not known. This study assessed the relation between measures of brain dopamine activity and indexes of motor and cognitive function in healthy individuals. METHOD: Thirty healthy volunteers aged 24-86 years were studied with positron emission tomography and [11C]raclopride to assess dopamine D2 receptors. All subjects underwent a neuropsychological test battery that included tasks found to be sensitive to dopamine alterations in patients with neurodegenerative disease and control tasks. RESULTS: Transfer of [11C]raclopride from plasma to brain in the striatum and cerebellum was not affected by age. In contrast, D2 receptor availability in the caudate and putamen declined with age. Correlations between D2 receptors and neuropsychological test performance were strongest for the motor task (Finger Tapping Test) and were also significant for most tasks involving frontal brain regions, including measures of abstraction and mental flexibility (Wisconsin Card Sorting Test) and attention and response inhibition (Stroop Color-Word Test, interference score). These relationships remained significant after control for age effects. CONCLUSIONS: Age-related decreases in brain dopamine activity are associated with a decline in motor function and may also contribute to impaired performance on tasks that involve frontal brain regions. Interventions that enhance dopamine activity may improve performance and quality of life for the elderly. The fact that correlations remained significant after age effects were partialed out suggests that dopamine activity may influence motor and cognitive performance irrespective of age.

Adult↗

PubMed1997

Functional MRI reveals left amygdala activation during emotion.

The potential of functional magnetic resonance imaging (fMRI) for experimental studies of the brain and behavior considerable given its superior time and spatial resolution, but few studies have attempted to validate them against established methods for measuring cerebral activation. In a previous study absolute regional cerebral blood flow was measured in 16 healthy individuals using quantitative H215O-PET during standardized happy and sad mood induction and during two non-emotional control conditions. During sad mood, blood flow increased in the left amygdala and these changes correlated with shifts towards a negative affect. In the present study blood oxygenation level dependent (BOLD) changes were measured with fMRI during the same experimentally controlled mood states and control tasks. Twelve right-handed normal subjects were examined with a T2*-weighted FLASH sequence. A significant increase in signal intensity was found during sad as well as happy mood induction in the left amygdala. This converging evidence supports the potential of fMRI for advancing the understanding of neural substrates for emotional experience in humans.

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PubMed1997

Neuropsychological evidence supporting a neurodevelopmental model of schizophrenia: a longitudinal study.

The stability of neuropsychological performance in schizophrenia and its relationship to clinical change was contrasted between 60 patients with schizophrenia (30 first-episode, 30 previously treated) and 38 healthy controls using a comprehensive neuropsychological battery and clinical scales administered at intake and at a 19-month follow-up. Consistent with the neurodevelopmental model of schizophrenia, patients demonstrated deficits in cognitive performance at initial testing and did not show decline at follow-up. There were no differences in neuropsychological performance over time between first-episode and previously treated patients, nor between male and female patients or controls. As expected, patients improved clinically with treatment with respect to both positive and negative symptoms. First-episode patients improved more on the positive symptoms of hallucination and delusion; male and female patients showed equivalent clinical improvement. Clinical improvement correlated positively with neuropsychological change, with improved negative symptomatology accounting for most of the significant correlations.

Adult↗

PubMed1997

Lateralized changes in regional cerebral blood flow during performance of verbal and facial recognition tasks: correlations with performance and "effort".

Functional neuroimaging has been used to investigate neural substrates of mnemonic processes, and cerebral blood flow (CBF) measures have been sensitive to activation with memory tasks. Studies of memory with two-dimensional 133Xenon clearance techniques found that word and face recognition tasks produced contralateral CBF changes in mid-temporal cortical regions. This study replicated the activation paradigm, expanding to the three-dimensional resolution of positron emission tomography (PET). Word and face recognition, and a control baseline task were administered to 19 healthy right-handed volunteers (11 men, 8 women) during successive 10 min PET 15O-water measures of CBF. Quantitative CBF rates were calculated with the arterial input function and the equilibrium model. Redistributions of blood flow were compared across tasks-using both absolute and relative (region/ whole brain) CBF. Replicating the 133Xenon clearance findings, CBF was "appropriately" lateralized during task performance (left-right for words > left-right for faces) in the mid-temporal region. Contrary to predictions, the recognition tasks did not activate expected mesolimbic or prefrontal areas. The task-induced CBF changes also correlated with performance. Bilateral CBF in mid-temporal and parahippocampal gyrus regions of interest correlated with the ability to correctly identify word targets (sensitivity). Left-lateralized CBF in the amygdala and hippocampus correlated with better word sensitivity as well as specificity (ability to correctly reject foils). Complementally, right-lateralized CBF in the parahippocampal gyrus correlated with better face specificity performance. In addition, left-lateralized CBF in the amygdala and right-lateralized CBF in the parahippocampal gyrus and hippocampus correlated with "mental effort" indices (task performance relative to basal ability) for word and face memory tasks, respectively. Thus, whereas this recognition task showed the expected lateralized increase in the mid-temporal region and not in frontal and limbic areas, lateralized activation in some of these areas was associated with better performance. Exploratory analyses on other regions showed lateralized changes in one additional temporal region, the occipital-temporal, and several limbic regions.

Adult↗

PubMed1997

Effects of aging on the cerebral distribution of technetium-99m hexamethylpropylene amine oxime in healthy humans.

Some brain functions decline at a linear rate throughout adulthood. Others remain relatively stable until very late in the life cycle. This study characterized the effects of aging on the regional cerebral distribution of hexamethylpropylene amine oxime (HMPAO) in healthy human volunteers. The sample consisted of 26 men and 18 women with a mean age of 41.6+/-14.9 years (range: 19-73). Their past medical histories, physical examinations, and laboratory screening tests were normal. Single-photon emission tomography (SPET) scans of the brain were performed with a standardized acquisition and processing protocol on a triple-headed camera equipped with fan beam collimators. A 3-D restorative filter and a correction for uniform attenuation were applied before the images were reinterpolated in planes parallel to the line connecting the frontal and occipital poles. Mean counts per pixel were measured in multiple regions of interest (ROIs) within each hemisphere by custom fitting a set of templates to the images. The mean activity in each ROI was compared with the mean activity per pixel in the whole brain. Regression analyses were used to relate the activity ratios to age with both linear and nonlinear models. The relative concentration of radioactivity decreased significantly with age in most, but not all, gray matter structures. It increased in the white matter regions. The nonlinear model of aging fit the data significantly better than a straight line did. Most of the changes with age occurred during young adulthood. No further changes were detectable after the onset of middle age. The median breakpoint age at which the rate of change became negligible was 36.6 years. Aging significantly affects the relative uptake of HMPAO in healthy humans. It decreases in many gray matter regions and increases in most white matter regions. However, the changes do not appear to be linear. Most seem to occur during young adulthood before people reach their late thirties. The distribution then appears to remain relatively stable throughout middle age.

Adult↗

PubMed1997

Attentional dysfunctions in neuroleptic-naive and neuroleptic-withdrawn schizophrenic patients and their siblings.

This study examined attentional deficits in 44 schizophrenic patients (24 neuroleptic-naive and 20 neuroleptic-withdrawn patients) across changes in medication status and clinical state using a 1-9 continuous performance test (CPT) with distractors. Patients' attentional selectivity scores (A') were unchanged from the off-medication to on-medication testings (on average, 6 months later), despite significant improvement in both positive and negative symptoms. Both patient groups had significantly lower A' scores than 44 matched healthy controls at each testing. The nonschizophrenic siblings (n = 15) of these patients made significantly more errors of omission and commission than healthy controls. The results suggest that attentional deficits, as measured by this CPT, appear to measure stable markers of schizophrenia that may be associated with genetic vulnerability to the illness.

Adolescent↗

PubMed1997

PET regional cerebral blood flow change during working and declarative memory: relationship with task performance.

Functional and anatomical relationships between working and declarative memory were investigated by contrasting regional cerebral blood flow (rCBF) change during standard working (Wisconsin Card Sorting Test, WCST) and declarative memory (Paired Associate Recognition Test, PART) tasks using identical stimulus-response modalities. The tasks and a resting baseline were administered to 30 participants (16 men, 14 women) during successive 10-min positron emission tomography 15O-water measures of rCBF. For both tasks, rCBF increased over baseline in inferior frontal and occipitotemporal regions, with more consistent dorsolateral prefrontal activation for WCST than PART. Additional orbitofrontal increases and dorsomedial decreases were seen for the PART. Activation patterns diverged when performance was considered. For the WCST, high performers activated dorsolateral and inferior frontal regions, whereas top PART performers activated only the occipitotemporal region. These results suggest operation of a frontotemporal network subserving both types of memory function that becomes more focal as performance increases.

Adolescent↗

PubMed1997

Olfactory identification deficits in schizophrenia: correlation with duration of illness.

OBJECTIVE: The authors examined the relationship between deficits in olfactory identification and duration of illness in young and elderly patients with schizophrenia. METHOD: Olfactory identification performance of 38 patients with schizophrenia and 40 normal subjects was compared by using the University of Pennsylvania Smell Identification Test. RESULTS: The schizophrenic patients demonstrated olfactory deficits relative to the comparison group, and the elderly schizophrenic patients displayed a greater magnitude of olfactory deficit than the younger patients. Independent of normal aging effects and cognitive deficit, patients with schizophrenia showed a strong relationship between olfactory identification scores and duration of illness, which suggests that olfactory abilities decline progressively over the course of the disorder. CONCLUSIONS: In contrast to other neuropsychological measures that have been reported to be stable over the course of illness, olfactory identification abilities deteriorate steadily in patients with schizophrenia, even for those with relatively recent onset.

Adolescent↗

PubMed1996

Relationships between verbal memory performance and the cerebral distribution of fluorodeoxyglucose in patients with schizophrenia.

Quantitative resting fluorodeoxyglucose-positron emission tomography scans were performed on 42 patients with schizophrenia. Magnetic resonance imaging-based regions of interest were transposed onto the corresponding positron emission tomography images. Region to whole brain ratios were calculated from the mean regional activity per pixel across both hemispheres (left plus right). Laterality scores were calculated from the difference between the mean activity in homotopic regions of the two hemispheres (left minus right). Subjects were tested contemporaneously with the Logical Memory subtest of the Wechsler Memory Scale. The subtest was scored with modified criteria to provide information about verbal recall, perseverations, and other components of verbal memory. Deficits in recall were associated with increased metabolism in selected regions of the left hemisphere that are known to mediate aspects of verbal memory. The findings support hypotheses suggesting that the left hemisphere is functionally overactive in schizophrenia.

Adolescent↗

PubMed1996

Assessing declarative memory in schizophrenia using Wisconsin Card Sorting Test stimuli: the Paired Associate Recognition Test.

The Paired Associate Recognition Test (PART) was developed to measure declarative memory using Wisconsin Card Sorting Test (WCST) stimuli, so that both tasks could be administered during functional neuroimaging to differentiate memory and executive function, and associated frontal and temporal lobe activation in schizophrenia. The current study was designed to compare PART and WCST performance in schizophrenic patients and to examine effects of medication and symptomatology. The PART, WCST, and standard declarative memory tasks were administered to 30 chronic schizophrenic patients and 30 matched healthy control subjects. Supporting task validity was the finding that patients were equally impaired on the PART and the WCST. Neuroleptics did not appear to affect performance. The effect of anticholinergic medication correlated negatively with WCST performance in a small subsample. Severity of schizophrenia-specific symptoms measured at intake on the Brief Psychiatric Rating Scale correlated negatively with performance on the WCST. These results support the application of the PART and WCST in future functional neuroimaging studies.

Adult↗

PubMed1996

Schizophrenia throughout life: sex differences in severity and profile of symptoms.

BACKGROUND: The impact of aging and of gender has been examined in health and disease, but has received limited attention in schizophrenia. A lifespan perspective of gender differences can contribute to an understanding of clinical features and their underlying neurobiological processes. METHOD: A prospective sample of 272 patients with schizophrenia, divided into four age groups: < 35, 35-65, 65-80 and > 85, was assessed with standardized procedures to measure the composition and severity of symptoms. RESULTS: Aging was associated with increased severity of symptoms and gender differences were noted. Negative symptoms increased in severity, while some positive symptoms ameliorated with aging. Women were characterized by reduced negative symptoms, and this remained evident until the eighth decade. CONCLUSIONS: Aging and gender moderate the clinical features of schizophrenia in specific symptom clusters. These effects may give insight into neurobiological substrates of the illness.

Adult↗

PubMed1996

Vulnerability to tardive dyskinesia development in schizophrenia: an FDG-PET study of cerebral metabolism.

An understanding of the development of tardive dyskinesia (TD) may require prospective studies assessing the relationship of brain function measures to behavior. This study was undertaken to determine whether predisposition to the development of TD is related to abnormalities of cerebral 18F-labeled 2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) measures in schizophrenia. A group of 42 patients without TD underwent FDG PET scanning for measuring cerebral metabolism as well as neuropsychological evaluation and magnetic resonance imaging. Patients were assessed longitudinally for TD development. Eight patients developed TD within 3 years. They were matched to eight patients without TD. Glucose metabolic rates and region/ whole brain ratios were examined in 38 regions of interest per hemisphere. Whole brain metabolism did not differ between the two groups. However, relative hypermetabolism in temporolimbic, brainstem, and cerebellar regions and hypoactivity in parietal and cingulate gyrus were found in the patients who later developed TD in contrast to those who did not. The groups were matched on clinical measures and had similar neuropsychological and neuroanatomic testing results. Thus, differences in the metabolic activity of specific brain regions are associated with vulnerability to TD development.

Adult↗

PubMed1996

Proactive inhibition and semantic organization: relationship with verbal memory in patients with schizophrenia.

Compared to other cognitive functions in schizophrenia, evidence suggests that verbal memory is particularly impaired. This study used the California Verbal Learning Test (CVLT) to examine proactive inhibition (PI) and semantic processing in verbal memory in 29 patients with schizophrenia and 29 healthy controls. Patients showed significantly less PI, but also did not organize (cluster) their recall according to semantic category. Controls and patients demonstrated small retroactive inhibition (RI) effects regardless of semantic content. Although both groups made similar types and numbers of free recall intrusion errors patients committed more phonemic and nonshared recognition errors. Results suggest that reduced semantic processing prevented build of PI, and contributes to defective memory in schizophrenia. The anatomic-physiologic abnormalities that underlie these findings may be particularly pronounced in prefrontal and temporal-parietal cortical areas.

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