Search PubMed⌕ Search

Biomedical subjects

R C Gur

Publications and source records attributed to R C Gur.

At least 73 records · Page 4Linked to original sources

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.

Adult↗

Cerebral blood flow changes in limbic regions induced by unsolvable anagram tasks.

OBJECTIVE: The study addressed the question of whether unsolvable as opposed to solvable cognitive problems activate discrete neuronal systems in the human brain. METHOD: Twelve healthy humans tried to solve unsolvable anagrams. Solvable anagrams and a resting baseline after each anagram task served as control conditions in a within-subject design. Activation was measured with the equilibrium infusion method by using 15O-labeled water and positron emission tomography, with absolute quantitation of anatomically defined regional cerebral blood flow (CBF). RESULTS: Compared to rest, both anagram tasks increased activity in frontal and temporal regions. The soluble task condition increased hippocampal activation and decreased mammillary bodies activity, while unsolvable anagrams were associated with increased CBF to the mamillary bodies and amygdala and decreased hippocampal activity. CONCLUSIONS: A limbic network integrating negative emotion and cognition seems reflected in reciprocal diencephalic and limbic activation with solvable and unsolvable anagrams. Since unsolvable anagrams have been used to induce learned helplessness in humans, this finding may provide an initial step toward clarifying its neural substrate.

Adult↗

Sex differences in neuroanatomical and clinical correlations in schizophrenia.

OBJECTIVE: The purpose of this study was to investigate sex differences in relationships between brain and behavior in schizophrenia. METHOD: Frontal lobe, temporal lobe, and whole brain volumes were obtained from magnetic resonance images of 91 patients with schizophrenia (54 men and 37 women) and 114 healthy comparison subjects (62 men and 52 women). Four independent symptom scales, based on the following symptom clusters, were derived from clinical data: negative, disorganization, Schneiderian hallucinations-delusions, and suspicion-hostility. Regression analyses incorporating the four clinical scales and neuroanatomical volumes were performed to investigate possible interactions between brain region and sex. RESULTS: Significant interactive effects of sex and frontal lobe volume were found in regression analyses of the disorganization and suspicion-hostility symptom scales. In men, higher frontal lobe volume was associated with milder severity of disorganization but was not correlated with severity of suspicion-hostility. In women, higher frontal lobe volume was associated with more severe disorganization as well as more severe suspicion-hostility. No associations were found between brain volume and severity of negative or Schneiderian symptoms. CONCLUSIONS: Differences between male and female patients were observed in the relationships between frontal lobe volume and two of the four clinical dimensions examined. These findings suggest that aspects of the neuropathological basis for some symptoms of schizophrenia may be sexually dimorphic.

Adolescent↗

Iodine-123-IPT SPECT imaging of CNS dopamine transporters: nonlinear effects of normal aging on striatal uptake values.

UNLABELLED: Iodine-123-labeled IPT (N-(3-iodopropen-2-yl)-2 beta-carbomethoxy-3 beta-(4-chlorophenyl)tropane) is an analog of cocaine that selectively binds the presynaptic dopamine transporter. This study sought to characterize changes in the striatal uptake of IPT with normal aging. METHODS: The sample included 18 healthy human volunteers. Their ages ranged from 19 to 67 yr. Dynamic SPECT scans of the brain were acquired with about 185 MBq (5 mCi) of IPT on a triple-headed camera. The images were reconstructed with a three-dimensional restorative filter and corrected for attenuation. The mean concentration of radioactivity [microCi/ml] was measured in the head of the caudate and body of the putamen. The remainder of the supratentorial brain was used as a reference. RESULTS: The specific uptake of IPT was higher in the caudate than in the putamen of each subject. It decreased significantly with age in both regions. The mean specific uptake in seven volunteers who were less than 30 yr old was 17.6 +/- 4.9 in the caudate and 13.3 +/- 4.0 in the putamen, compared to only 11.97 +/- 3.30 and 7.8 +/- 2.68, respectively, in the six middle-aged subjects (t = 2.53 and 2.90, df = 11, p = 0.027 and 0.014). However, there were no significant differences between the six middle-aged subjects and the five volunteers who were older than 60 yr, whose respective means were 9.0 +/- 1.6 and 6.2 +/- 0.7 (t = 1.83 and 1.28, df = 9, p = 0.10 and 0.23). The results were supported by regression analysis, which indicated that changes with age were not optimally described as a linear function when compared to several nonlinear alternatives. The fit improved when the models accounted for relatively rapid rates of decline during young adulthood, followed by less rapid decline throughout middle age. CONCLUSION: The results are consistent with the findings from previous studies that have shown that the specific uptake values for radiopharmaceuticals that bind the dopamine transporter decline with advancing age. However, results of this study suggest that the effects of aging may be nonlinear and regionally distinct.

Adult↗

Mood effects on limbic blood flow correlate with emotional self-rating: a PET study with oxygen-15 labeled water.

Positron emission tomography was used to study the effects of experimentally controlled mood states on cerebral blood flow (CBF), measured with the quantitative equilibrium infusion method and 15O-labeled water. Twenty-seven brain regions in each hemisphere were assessed in 16 normal subjects. CBF and heart rate were measured during happy and sad mood induction, and during two nonemotional control conditions: sex differentiation and resting baseline. Valence-specific effects of mood on CBF were obtained for subcortical, but not for frontal-temporal or control regions. CBF increased in left amygdala and decreased in right amygdala during sad mood relative to the averaged control conditions. These changes correlated with shifts toward negative affect. Correlations were opposite for subcortical (negative affect associated with lower left hemispheric CBF) compared with frontal-temporal cortical regions. Results support limbic involvement in regulating emotional states and suggest some reciprocity between subcortical and frontal-temporal regulation of emotional experience.

Adolescent↗

Sex differences in regional cerebral glucose metabolism during a resting state.

Positron emission tomography was used to evaluate the regional distribution of cerebral glucose metabolism in 61 healthy adults at rest. Although the profile of metabolic activity was similar for men and women, some sex differences and hemispheric asymmetries were detectable. Men had relatively higher metabolism than women in temporal-limbic regions and cerebellum and relatively lower metabolism in cingulate regions. In both sexes, metabolism was relatively higher in left association cortices and the cingulate region and in right ventro-temporal limbic regions and their projections. These results are consistent with the hypothesis that differences in cognitive and emotional processing have biological substrates.

Adult↗

Frontal and temporal lobe brain volumes in schizophrenia. Relationship to symptoms and clinical subtype.

BACKGROUND: Quantitative magnetic resonance imaging (MRI) studies demonstrate reduced brain volumes in schizophrenics, but specific structural abnormalities have not been clearly delineated. The structural abnormalities of this disorder are likely to be heterogeneous, consistent with its diverse clinical presentation. To investigate the relationship between structural abnormality and clinical symptoms, we examined regional brain and cerebral spinal fluid (CSF) volumes in a large sample of schizophrenic patients and controls, with patients aggregated into clinical subtypes. METHODS: Right and left hemisphere frontal and temporal lobe brain and CSF volumes were quantified from 5-mm axial spin-echo MRIs for 71 schizophrenic patients and 77 age- and sex-matched controls. The following four standardized rating scales were used to assess symptom severity: Negative Symptoms, Disorganization, Schneiderian Delusions and Hallucinations, and Suspicion-Hostility. Patients were also subtyped as either deficit or nondeficit on the basis of enduring negative symptoms. RESULTS: Schizophrenic patients overall exhibited abnormal brain asymmetry, with selective decrease in brain volume in the left temporal and right frontal regions. Left temporal lobe parenchymal volume reduction and CSF volume increase were correlated with the severity of negative symptoms. Consistent with this, the subtype analysis revealed abnormal temporal lobe asymmetry for the deficit subgroup only. Right frontal lobe volume reduction correlated with the duration of illness, independent of symptom severity or schizophrenic subtype. CONCLUSIONS: Abnormal lateral asymmetry suggests selective structural deficits in schizophrenia, rather than diffusely undifferentiated CNS abnormalities. The pattern of regional abnormalities is related to clinical symptoms, with negative symptoms being associated with left temporal lobe rather than frontal lobe abnormality. This is consistent with suggestions of a temporolimbic prefrontal network abnormality in schizophrenia. Further longitudinal studies are warranted, using higher-resolution MRI technology and gray matter-white matter segmentation to confirm and extend these findings.

Adolescent↗

Evaluation of age-related changes in serotonin 5-HT2 and dopamine D2 receptor availability in healthy human subjects.

We assessed the relation between serotonin 5-HT2 receptor availability and aging and compared it with that for dopamine D2 receptors on 19 healthy male volunteers (age range, 21-49 years) using positron emission tomography (PET) and F-18 N-methylspiperone (NMS). 5-HT2 Receptor availability was obtained using the ratio of the distribution volume in the region of interest to that in the cerebellum (Bmax'/Kd' + 1). 5-HT2 Receptor measures were obtained in frontal and occipital cortices. D2 receptor availability in striatum was measured using the "ratio index". 5-HT2 Receptor availability decreased significantly with age. This effect was significantly more accentuated for 5-HT2 receptor availability in the frontal (r = 0.92, p < or = 0.0001) than in the occipital (r = 0.67, p < or = 0.0016) cortex (df = 1, p < 0.025). Dopamine D2 receptors were also found to decrease significantly with age (r = 0.63, p < or = 0.007). In a given subject, striatal D2 receptor availability significantly correlated with 5-HT2 receptor availability in the frontal (r = 0.51, p < or = 0.035) but not in the occipital cortex. These results document a decline in 5-HT2 and D2 receptor availability with age and showed an association between frontal 5-HT2 and striatal D2 receptors.

Adult↗

Emotional processing in schizophrenia: neurobehavioral probes in relation to psychopathology.

The application of neurobehavioral methods in functional neuroimaging can provide useful information on the neurobiology of schizophrenia. This process can be enhanced by using a standard set of procedures to construct 'neurobehavioral probes' which are suitable for functional imaging and provide reliable measures discriminating patients from healthy controls. While such probes are available for cognitive tasks, none has been applied to study emotional processing in schizophrenia. We examined emotional discrimination and experience probes and correlated performance with cognitive and clinical measures. Emotion discrimination tasks and mood induction procedures with happy, sad, and neutral facial expressions were administered to 40 patients with schizophrenia. Neuropsychological testing assessed intellectual, attention, abstraction-flexibility, memory, language, spatial, and sensory-motor functions. Emotional performance was compared to a group of 40 normal subjects. Performance for face discrimination was impaired in patients. There was specific impairment in discrimination of happy expressions. Mood induction was effective in both groups, but diminished in patients, especially for happiness. Poorer performance in emotion discrimination correlated with severity of negative symptoms and bizarre behavior. Hallucinations were associated with more pronounced mood induction effects. Emotion discrimination was also correlated with abstraction, memory, language and spatial tasks, while mood induction effects showed no such associations. Thus, the impairment in discriminating and experiencing valence-specific emotions in schizophrenia relates to symptomatology and neuropsychological functioning. The results encourage the use of the emotion discrimination task and the mood induction procedure as neurobehavioral probes in physiologic neuroimaging studies for investigating the neural substrates of emotion.

Adult↗

Language before and after temporal lobectomy: specificity of acute changes and relation to early risk factors.

We evaluated language functions in 154 patients with left hemisphere speech dominance undergoing anterior temporal lobectomy (ATL). Measures of phonemic and semantic fluency, confrontation naming, repetition, comprehension, and reading were administered before and 3 weeks postoperatively. Patients were grouped by focus (left, LT; right, RT) and presence of early risk factors for development of seizures (ER, early risk, < or = 5 years; NER, no early risk): (LT-ER, n = 45; RT-ER, n = 49; LT-NER, n = 27; RT-NER, n = 33). Preoperatively, the LT group showed a selective naming deficit as compared with the RT group. Postoperatively only the LT-NER group showed significant overall decline in language. For this group, the change was attributable to a selective decline in naming as compared with other functions. These data indicate that there is a specific risk to naming after dominant ATL for adult temporal lobe epilepsy (TLE) patients with a left hemisphere focus and the absence of an early risk factor for the development of seizures.

Aphasia↗

Prospective clinicopathologic studies of schizophrenia: accrual and assessment of patients.

OBJECTIVE: The purpose of this study was to characterize the neuropsychiatric profile of elderly patients with schizophrenia and establish a patient registry for prospective ante-mortem and post-mortem studies. METHOD: Medical records of all chronically institutionalized patients in eight state hospitals who were over the age of 65 and had a chart diagnosis of schizophrenia (N = 528) were reviewed. Of the potential subjects, 192 were excluded because of clinical histories inconsistent with a diagnosis of schizophrenia, 56 because of insufficient information to establish a psychiatric diagnosis, and 122 because of family members' refusal to give consent for autopsy in the event of death. To date, 81 of the remaining 158 patients have undergone neuropsychiatric evaluation with standard assessment instruments. RESULTS: Mini-Mental State scores of the 81 patients indicated severe dementia, and Functional Assessment Scale scores showed that patients required assistance with activities of daily living. All patients were rated as severely ill on the Brief Psychiatric Rating Scale. Ratings on the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms indicated a predominance of negative symptoms over positive. Of 30 patients who have died to date, research autopsies have been conducted on 26. CONCLUSIONS: Establishing a well characterized, prospective patient registry for clinicopathologic studies of schizophrenia is feasible but labor intensive. Diagnosis of schizophrenia with a high degree of confidence can be achieved by means of detailed chart review and assessment of current neuropsychiatric functioning with standard rating instruments. These data provide a basis for correlations of clinicopathologic factors.

Activities of Daily Living↗

Smaller neuron size in schizophrenia in hippocampal subfields that mediate cortical-hippocampal interactions.

OBJECTIVE: The goal of this study was to characterize the hippocampal formation in patients with schizophrenia by measuring neuron density, neuron size, and variability of neuronal axis orientation. METHOD: Brain tissue was obtained at autopsy from 14 prospectively accrued elderly patients with chronic schizophrenia and 10 age-compatible individuals without psychiatric disorder. Eight hippocampal regions of interest and two internal control regions (primary motor and visual cortices) were identified on Nissl-stained sections. Morphometric measurements were made without knowledge of diagnosis by means of a computer-based image analysis system. RESULTS: The patients exhibited smaller neuron size in the hippocampal regions relative to the control regions, which was significant only for the subiculum, CA1, and layer II of the entorhinal cortex. Neuron size in the control regions was nearly identical in the two groups. No significant differences in neuron density or in variability of neuronal axis orientation were identified for any region. There was no correlation between neuron size in any area and several potentially confounding variables (age, post-mortem interval, neuroleptic exposure, sex, brain hemisphere studied, duration of illness), with the exception of a negative correlation with age in layer II of the entorhinal cortex. Regression analyses indicated that the findings could not be attributed to these age effects. CONCLUSIONS: The subiculum, entorhinal cortex, and CA1 are the major subfields of the hippocampal region that maintain the afferent and efferent connections of the hippocampus with widespread cortical and subcortical targets. The smaller size of neurons in these subfields may reflect the presence of structural or functional impairments that disrupt these connections, which in turn could have important behavioral sequelae.

Age Factors↗

Normative neuropsychological test performance: effects of age, education, gender and ethnicity.

Normative data on neuropsychological test performance for a sample of 131 adults (ages 18-49) is presented. All subjects were native speakers of English screened for past or present medical, neurological and psychiatric disorders, including substance abuse. A broad-based battery including measures of intellectual skills, memory and learning, receptive and expressive language, auditory and visual information processing and attention, sensory processing, motor skills, and self-reported anxiety and depression was administered. Means, standard deviations and percentile rankings for all tests are reported. Regression analyses were computed to consider the concurrent influence of sociodemographic factors on all tests. Significant effects of age (M=27.1 yrs), education (M=14.6 yrs), gender (58% male), and ethnicity (62% white) were observed for relatively few test scores. Younger age at testing was associated with better continuous performance test scores. Higher education levels were associated with higher vocabulary and reading scores. Males had higher WAIS-R Information scores and faster Finger Tapping scores compared to females Ethnicity was associated with Full-scale IQ, and additional tests with a verbal component, e.g., Boston Naming Tests, and non-verbal component, e.g., Drawing Tests. We conclude that sociodemographic factors infrequently account for more than 10% of the variance for many neuropsychological test scores.

Journal Article↗

Reading on the Wide Range Achievement Test-Revised and parental education as predictors of IQ: comparison with the Barona formula.

It is frequently necessary in research and clinical evaluations to obtain estimates of premorbid intelligence (IQ) which are separate from measured IQ. There is evidence that word reading may be useful in this aim. In order to determine the potential of the Wide Range Achievement Test-Revised (WRAT-R) reading subtest (READ) as an estimate of premorbid IQ, the present study examined the relationship between READ and IQ in healthy subjects. Consistent with other findings, READ accounted for a significant amount of variance in Verbal, Performance, and Full Scale IQ. Race and parental education, the latter being a variable not previously examined in this literature, accounted for incrementally valid variance in IQ beyond READ. The predictive power of these variables compares favorably with estimates made by the Barona IQ estimation formula, which uses only demographic information.

Journal Article↗

Cerebral blood flow in schizophrenia: effects of memory processing on regional activation.

Regional cerebral blood flow (rCBF) was measured with the 133Xenon clearance technique and a high resolution (254 detectors) scanner during the performance of a verbal and a facial memory task in 18 patients with schizophrenia and 18 sociodemographically matched controls. Patients and controls had comparable resting rCBF, but differed in global and hemispheric rCBF changes induced by the memory tasks. Patients had less global increase, which was relatively higher in the left hemisphere, and this was more pronounced for the verbal task. Although controls showed appropriate laterality changes (L > R for verbal and R > L for facial memory) in the midtemporal region, patients failed to show such a focal pattern. They did not show appropriate laterality change in the midtemporal region, but instead showed such changes in other regions. Patients showed greatest impairment in specificity of verbal recognition performance, and this correlated with severity of hallucinations and delusions. This supports a model of left temporal lobe dysfunction in schizophrenia.

Adult↗

Neuropsychological deficits in neuroleptic naive patients with first-episode schizophrenia.

BACKGROUND: Medication and chronicity have complicated past attempts to characterize the neuropsychological performance of patients with schizophrenia. There have been inconsistencies regarding the pattern, selectivity, and sources of observed deficits. Our objective was to comprehensively examine neuropsychological function in patients with schizophrenia who had never been exposed to neuroleptic medication, and who were experiencing their first episode (FE) of psychosis. METHODS: Subjects were consecutive recruitments that included 37 patients with FE schizophrenia who were never exposed to neuroleptics. These subjects were compared with 65 unmedicated, previously treated (PT) patients and 131 healthy controls. RESULTS: The patients groups had nearly identical profiles showing generalized impairment, particularly in verbal memory and learning, attention-vigilance, and speeded visual-motor processing and attention. Verbal memory and learning accounted for most of the variance between patients and controls and removing this effect substantially attenuated all other differences. By contrast, both the FE group and PT group continued to show highly significant deficits in verbal memory and learning after controlling for attention, abstraction, and all other functions. Some functions not typically implicated in schizophrenia (spatial cognition, fine motor speed, and visual memory) were more impaired in the PT group than in the FE group. CONCLUSIONS: Verbal memory, as a primary neuropsychological deficit present early in the course of schizophrenia, implicates the left temporal-hippocampal system. Neuropsychological evaluations before treatment permit differentiation of primary deficits from changes secondary to medication or chronicity. This is essential for developing a neurobehavioral perspective on schizophrenia.

Adult↗

Neuropsychological functioning in siblings discordant for schizophrenia and healthy volunteers.

OBJECTIVE: To determine whether schizophrenics and their nonschizophrenic siblings have a similar pattern of neuropsychological deficit when compared with normal controls. DESIGN AND PARTICIPANTS: Fifteen probands with schizophrenia, 16 of their nonschizophrenic siblings, and 31 unrelated, demographically balanced, normal individuals underwent evaluation with a comprehensive neuropsychological test battery. All subjects were screened for history of head injury, neurologic illness, major medical conditions, substance use, and axis I psychiatric disorders other than schizophrenia. Probands underwent evaluation twice: once at intake when half had never received neuroleptic medication and the other half had received none for a minimum of 2 weeks, and again at the 2- to 4-week follow-up, after stabilization with neuroleptic medications. RESULTS: Both schizophrenics and their nonschizophrenic siblings were impaired neuropsychologically compared with normal controls, with the nonschizophrenic siblings' performance intermediate between that of the schizophrenic siblings and the normal controls on all measures of functioning. The shapes of the deficit profiles of schizophrenic patients and their siblings were similar; in patients, verbal memory, abstraction, attention, and language functions were significantly more affected compared with spatial abilities, spatial memory, and sensory-motor functions, with a nonsignificant trend in the same direction in siblings. Cognitive functioning in patients was found to be stable across changes in medication status and clinical state. Four fifths of patients obtained more deviant scores than their nonschizophrenic siblings. Among the sibling group, those with probable and certain diagnoses of schizotypal personality disorder were more impaired compared with those without schizophrenia-spectrum symptoms. CONCLUSION: These results support the hypothesis that impaired information processing aggregates in the family members of schizophrenics and may serve as an indicator of genetic vulnerability to the disorder. Further work is needed to establish whether particular areas of functioning are selectively impaired in relatives and to determine whether the performance deficits are mediated by structural and/or metabolic disturbances in specific brain regions.

Adult↗