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R S Kahn

Publications and source records attributed to R S Kahn.

At least 37 records · Page 2Linked to original sources
PubMed2004

Increasing dopaminergic activity: effects of L-dopa and bromocriptine on human sensory gating.

Schizophrenic patients show a loss of sensory gating, which is reflected in a reduced P50 suppression. Because most of the symptoms in schizophrenia can be reduced by antagonists of the dopaminergic (D2) system, the loss in sensory gating might be related to an increased dopaminergic activity. Therefore, in the present study, the effects of increased dopaminergic neurotransmisson on sensory gating in healthy volunteers were investigated. In a double-blind, balanced, placebo-controlled design, healthy male volunteers were challenged in two separate studies with either 300 mg L-dopa (precursor of dopamine) or placebo (n=16) and 1.25 mg bromocriptine (D2 agonist) or placebo (n=17). Subsequently, they were tested for their sensory gating (P50 suppression). P50 suppression values in the placebo condition were comparable to those found in literature. Although both L-dopa and bromocriptine reduced P50 amplitude, they did so in an equal ratio for both the response to the conditioning (C) and the testing (T) stimuli, therefore not resulting in a reduction of the P50 suppression ratio (T/C). In the present study, neither L-dopa nor bromocriptine reduced sensory gating in healthy volunteers. This suggests that an increased dopaminergic activity in humans is not responsible for the reduction in sensory gating as seen, for example, in schizophrenia.

Acoustic Stimulation↗
PubMed2003

Neurophysiological factors in human information processing capacity.

What determines how well an individual can manage the complexity of information processing demands when several tasks have to be executed simultaneously? Various theoretical frameworks address the mechanisms of information processing and the changes that take place when processes become automated, and brain regions involved in various types of information processing have been identified, as well as sequences of events in the brain. The neurophysiological substrate of human information processing capacity, i.e. the amount that can be processed simultaneously, is, however, unresolved, as is the basis of inter-individual variability in capacity. Automatization of cognitive functions is known to increase capacity to process additional tasks, but behavioural indices of automatization are poor predictors of processing capacity in individuals. Automatization also leads to a decline of brain activity in the working memory system. In this study, we test the hypothesis that processing capacity is closely related to the way that the brain adjusts to practice of a single cognitive task, i.e. to the changes in neuronal activity that accompany automatization as measured with functional MRI (fMRI). Using a task that taxes the working memory system, and is sensitive to automatization, performance improved while activity in the network declined, as expected. The key finding is that the magnitude of automatization-induced reduction of activity in this system was a strong predictor for the ability to perform two different working memory tasks simultaneously (after scanning). It explained 60% of the variation in information processing capacity across individuals. In contrast, the behavioural measures of automatization did not predict this. We postulate that automatization involves at least two partially independent neurophysiological mechanisms, i.e. (i) streamlining of neuronal communication which improves performance on a single task; and (ii) functional trimming of neuronal ensembles which enhances the capacity to accommodate processing of additional tasks, potentially by facilitating rapid switching of instruction sets or contexts. Finally, this study shows that fMRI can provide information that predicts behavioural output, which is not provided by overt behavioural measures.

Adult↗
PubMed2003

Language lateralization in female patients with schizophrenia: an fMRI study.

Gender differences in schizophrenia are among the most consistently reported findings in schizophrenia research. However, the biological substrate underlying these gender differences is still largely unknown. Differences in language lateralization between men and women may underlie some gender differences in schizophrenia. In previous functional imaging studies, language lateralization was found to be decreased in male schizophrenia patients as compared to healthy males, which was due to enhanced language activation of the right hemisphere as compared to the healthy males. It could be hypothesized that decreased language lateralization in schizophrenia is gender specific, i.e. decreased lateralization in male patients and normal lateralization in female patients. To test this hypothesis, language activation was measured in 12 right-handed female patients with schizophrenia and 12 healthy females, and compared to findings in 12 male patients and 12 male controls of an earlier study. Language lateralization was significantly lower in the female patients (0.44) as compared to the female controls (0.75), which was due to increased activation of the right-sided language areas (patients: 19 voxels; controls: 8 voxels), while left hemisphere activation was similar in patients and controls. When these data are compared to the male patients and controls, both patient groups had lower lateralization than their healthy counterparts, but there was no difference between male and female patients. In both sexes, decreased lateralization resulted from increased right hemispheric language activation, which suggests a failure to inhibit nondominant language areas in schizophrenia. These findings indicate that lower language lateralization in women is not likely to underlie gender differences in schizophrenia.

Adult↗
PubMed2003

Relapse prevention in patients with schizophrenia.

This article describes the development and content of a nursing intervention protocol for the recognition of the early signs of psychosis. Applying this protocol, nurses can contribute to the prevention of psychotic relapse in patients with schizophrenia or a related disorder. The background and construction of the intervention protocol are described. The judgment of experts in the care of patients with schizophrenia on the content and applicability of the protocol is presented. Finally, the experience is summarized that has been acquired during the conduct of a number of case studies of the application of the intervention protocol.

Attitude of Health Personnel↗
PubMed2002

[A bifid uvula in a patient with schizophrenia as a sign of 22q11 deletion syndrome].

A bifid uvula and nasal speech were observed in a 25-year-old woman who was referred because of psychotic complaints. Fluorescence in situ hybridisation (FISH) research for the 22q11 deletion was carried out and the deletion was found. The 22q11-deletion syndrome (22q11DS) is characterised by somatic abnormalities including cardiovascular defects, velopharyngeal anomalies and typical facial characteristics. There is an increasing interest in the cognitive and psychiatric consequences of 22q11DS. There is a high prevalence of learning disabilities and the delayed development of language and speech. Mild mental retardation or borderline intellectual functioning is often reported. A broad range of psychiatric symptoms have been reported; a consistent finding is the development of a psychosis in a considerable proportion of 22q11DS patients from early adulthood onwards. It is important to consider the possibility of 22q11DS in psychiatric patients, as then early intervention strategies for later psychopathological abnormalities are possible, as well as the provision of genetic counselling.

Abnormalities, Multiple↗
PubMed2002

Does the Schizotypal Personality Questionnaire reflect the biological-genetic vulnerability to schizophrenia?

We investigated whether the Schizotypal Personality Questionnaire (SPQ) [Schizophr. Bull. 17 (1991) 555.] could be an indicator of the biological-genetic vulnerability to schizophrenia. We hypothesized that the mean scores on three dimensions of the SPQ of different groups of relatives of patients with schizophrenia would parallel their risk for developing schizophrenia. The SPQ was administered to 51 first-episode schizophrenia patients, 63 parents of schizophrenia patients, 42 siblings of schizophrenia patients and 12 children of schizophrenia patients. Patients differed from the relatives on all three dimensions. Siblings and children scored significantly higher than parents on Positive Schizotypy, and the insignificant difference between the siblings and children was in the expected direction. The results could not be explained by the differences in age, sex, IQ or substance abuse. No differences were found for Disorganization Schizotypy between the relatives. Children scored higher than parents on Negative Schizotypy. The current study offers support to the hypothesis that the positive dimension of SPQ reflects the genetic vulnerability to schizophrenia.

Adult↗
PubMed2002

The practice of early recognition and early intervention to prevent psychotic relapse in patients with schizophrenia: an exploratory study. Part 2.

In this article we describe the findings of an exploratory study into the application of early recognition and early intervention methods aimed at prevention of psychotic relapses in patients with schizophrenia. Following the results we described in part 1, we now focus specifically on factors which favourably or adversely affect the use of early recognition and early intervention methods. The following issues will be addressed: (i) information and education; (ii) attitude of health care professionals; (iii) the patient's insight; (iv) acceptance of illness; (v) motivation; (vi) other relevant patient characteristics; and (vii) continuity of care. Finally, the implications of the findings for the development of a nursing intervention protocol will be discussed.

Attitude of Health Personnel↗
PubMed2002

The practice of early recognition and early intervention to prevent psychotic relapse in patients with schizophrenia: an exploratory study. Part 1.

In this article we describe the findings of an exploratory study into the application of early recognition and early intervention methods aimed at prevention of psychotic relapses in patients with schizophrenia. We addressed several models of symptom recognition plans and indicated how patients, healthcare professionals and other persons involved may be able to list and evaluate early warning signs systematically. We also paid attention to the role of the patient's family and to the potential effects of using early recognition and early intervention methods. In a follow-up article (part 2), we will focus more specifically on factors which favourably or adversely affect the use of early recognition and early intervention methods. The results of this exploratory study will be used to design an intervention protocol for nursing staff to serve as a tool for preparing symptoms recognition plans with the individual patient and his/her social network.

Adult↗
PubMed2002

Excessive recruitment of neural systems subserving logical reasoning in schizophrenia.

Schizophrenic patients generally perform poorly on tasks that address executive functions. According to several imaging studies, the dorsolateral prefrontal cortex is hypoactive in schizophrenic patients during these tasks. It is not, however, clear whether this finding is associated more with impaired performance than with the illness itself, as performance has not been taken into account. We examined brain activity associated with executive function in schizophrenia using an experimental fMRI design that reveals performance effects, enabling correction for performance differences between groups. As this approach has not been reported before, and because brain function can be affected by medication, the effect of antipsychotic medication was also investigated. A task was used that requires logical reasoning, alongside a closely matched control task. Performance was accounted for by including individual responses in fMRI image analyses, as well as in group-wise analysis. Effects of medication were addressed by comparing medication-naïve patients and patients on atypical antipsychotic medication with healthy controls in two separate experiments. Imaging data were analysed with a novel, performance-driven method, but also with a method that is similar to that used in earlier studies, which reported hypofrontality. A modest reduction in performance was found in both patient groups. Brain activity associated with logical reasoning was correlated positively with performance in all groups. In patients on medication, activity did not differ from that in controls after correcting for difference in performance. In contrast, performance-corrected activity was significantly elevated in medication-naïve patients. This study indicates that schizophrenia may be associated with excessive recruitment of brain systems during logical reasoning. Considering the fact that performance was reduced in the patients, we argue that the efficiency of neural communication may be affected by the illness. It appears that in patients on atypical antipsychotic medication, this neural inefficiency is normalized. The study shows that performance is an important factor in the interpretation of differences between schizophrenic patients and controls. The reported association between performance and brain activity is relevant to clinical imaging studies in general.

Adult↗
PubMed2002

Language lateralization in monozygotic twin pairs concordant and discordant for handedness.

An unexpectedly high percentage of monozygotic twin pairs is discordant for handedness. Some of these twins show mirror-imaging of several ectodermally derived features. Both features of discordant left-right asymmetry may be caused by relatively late monozygotic twinning, when the original embryo has already lost its bilateral symmetry. Language lateralization is related to handedness and may therefore also be altered during the development of embryological asymmetry in some monozygotic twins. Language lateralization was measured with functional MRI in 12 monozygotic twin pairs who were concordant for handedness and in 13 monozygotic twin pairs discordant for handedness. Lateralization indices were calculated from individual language activation patterns. Correlations were calculated to test intra-pair resemblance for language lateralization. The intra-pair correlation for language lateralization was significant in the handedness-concordant group, but not in the handedness-discordant group. In the handedness-discordant group, five twin pairs were also discordant for cerebral dominance; the other twin pairs of discordant handedness exhibited remarkable similarity in language lateralization. The high intra-pair correlation for language lateralization in the handedness-concordant twins suggests a genetic basis for language lateralization. However, in monozygotic twin pairs of discordant handedness, discordance for language dominance occurs in a significant number of twins. Discordant language dominance may be caused by a relatively late time of splitting of the original embryo, which disrupts the normal development of left-right asymmetry.

Female↗
PubMed2002

Brain morphology in antipsychotic-naïve schizophrenia: a study of multiple brain structures.

BACKGROUND: Although brain volume changes are found in schizophrenia, only a limited number of structural magnetic resonance imaging studies have exclusively examined antipsychotic-naïve patients. AIMS: To comprehensively investigate multiple brain structures in a single sample of patients who were antipsychotic-naïve. METHOD: Twenty antipsychotic-naïve patients with first-episode schizophrenia and 20 healthy comparison subjects were included. Intracranial, total brain, frontal lobe, grey and white matter, cerebellar, hippocampal, parahippocampal, thalamic, caudate nucleus and lateral and third ventricular volumes were measured. Repeated-measures analyses of (co)variance were conducted with intracranial volume as covariate. RESULTS: Third ventricle volume enlargement was found in patients compared with the healthy subjects. No differences were found in other brain regions. CONCLUSIONS: These findings suggest that some brain abnormalities are present in the early stages of schizophrenia. Moreover, it suggests that brain abnormalities reported in patients with chronic schizophrenia develop in a later stage of the disease and/or are medication induced.

Adolescent↗
PubMed2001

Differentiating between low and high susceptibility to schizophrenia in twins: the significance of dermatoglyphic indices in relation to other determinants of brain development.

Both the skin and the brain develop from the same ectoderm and it is thought, therefore, that dermatoglyphics are informative for early disturbances in brain development in schizophrenia. This study was aimed at investigating the differences in both digital and palmar dermatoglyphic indices between twins discordant for schizophrenia and control twins. Furthermore, the significance of dermatoglyphic indices in relation to other determinants of brain development with regard to the susceptibility to schizophrenia was investigated. Data on dermatoglyphic indices of the hand and the palm were obtained from 21 same-sex discordant and 37 same-sex control twins. For 19 discordant and 25 control twins, there was also data available on brain volumes. Non-genetic intra-uterine circumstances early in pregnancy (10-13 weeks of gestation) are associated with a susceptibility to schizophrenia, since both the twins with schizophrenia and the unaffected co-twins showed more fluctuating asymmetry of the finger ridges (P<0.01), and marginally higher absolute finger ridge counts (P=0.06) than control twin pairs. Fluctuating asymmetry of the finger ridges was as important as whole brain and left hippocampal volumes in differentiating twins with a high susceptibility to schizophrenia from those with a low susceptibility.

Adult↗
PubMed2001

Language lateralization in schizophrenia, an fMRI study.

Anatomical studies have shown that cerebral asymmetry is reduced in schizophrenia. Functional asymmetry appears to be reduced also, as was shown with dichotic listening studies. These studies, however, have not revealed whether reduced lateralization is the result of decreased language activity of the left hemisphere or whether it is the consequence of increased language-related activity in the right hemisphere. To elucidate this, we examined hemispheric dominance for language processing by means of functional MRI. Twelve schizophrenic patients and twelve healthy controls were scanned while they were engaged in a verb-generation and a semantic decision task. Activation was measured bilaterally in the frontal, temporal and temporo-parietal language areas, and a laterality index was derived from activity in these regions of interest in the left and the right hemispheres. Clinical symptoms were rated at the time of scanning. The results indicate that language processing is less lateralized in patients than in controls (a mean laterality index of 0.35 versus 0.63, respectively, difference p<0.01). Analysis of variance of the extent of activity, i.e. numbers of active voxels, revealed a significant hemisphere by group interaction (F(1,22)=11.2, p<0.001), which was due to increased activation in the right hemisphere of the patients (post hoc t-test p<0.05). We found no evidence of reduced activity in the left hemisphere. Further analysis of clinical symptoms rated prior to scanning revealed that decreased language lateralization was associated with more severe hallucinations (r=-0.54, p<0.05). We postulate that decreased language lateralization in schizophrenia may result from failure to inhibit the right hemisphere.

Adult↗
PubMed2001

Functional anatomical correlates of controlled and automatic processing.

Behavioral studies have shown that consistent practice of a cognitive task can increase the speed of performance and reduce variability of responses and error rate, reflecting a shift from controlled to automatic processing. This study examines how the shift from controlled to automatic processing changes brain activity. A verbal Sternberg task was used with continuously changing targets (novel task, NT) and with constant, practiced targets (practiced task, PT). NT and PT were presented in a blocked design and contrasted to a choice reaction time (RT) control task (CT) to isolate working memory (WM)-related activity. The three-dimensional (3-D) PRESTO functional magnetic resonance imaging (fMRI) sequence was used to measure hemodynamic responses. Behavioral data revealed that task processing became automated after practice, as responses were faster, less variable, and more accurate. This was accompanied specifically by a decrease in activation in regions related to WM (bilateral but predominantly left dorsolateral prefrontal cortex (DLPFC), right superior frontal cortex (SFC), and right frontopolar area) and the supplementary motor area. Results showed no evidence for a shift of foci of activity within or across regions of the brain. The findings have theoretical implications for understanding the functional anatomical substrates of automatic and controlled processing, indicating that these types of information processing have the same functional anatomical substrate, but differ in efficiency. In addition, there are practical implications for interpreting activity as a measure for task performance, such as in patient studies. Whereas reduced activity can reflect poor performance if a task is not sensitive to practice effects, it can reflect good performance if a task is sensitive to practice effects.

Adult↗
PubMed2001

Volumes of brain structures in twins discordant for schizophrenia.

BACKGROUND: The study was designed to examine the relative contributions of genetic and nongenetic factors to structural brain abnormalities in schizophrenia and subjects at risk to develop the disorder. METHODS: The brains of 15 monozygotic and 14 same-sex dizygotic twins discordant for schizophrenia (patients) and 29 healthy twins pair-wise matched for zygosity, sex, age, and birth order were studied using high-resolution magnetic resonance imaging scans. RESULTS: Intracranial and whole-brain corrected frontal lobe volumes were smaller (4.6% and 2.7%, respectively) in discordant monozygotic twins as compared with healthy monozygotic twins. Irrespective of zygosity, discordant twins had smaller whole-brain (2%), parahippocampal (9%), and hippocampal (8%) volumes than healthy twins. Moreover, patients had smaller whole-brain volumes (2. 2%) than their nonschizophrenic cotwins, who in turn had smaller brains (1%) than healthy twins. Lateral and third-ventricle volumes were increased in discordant dizygotic twins as compared with healthy dizygotic twins (60.6% and 56.6%, respectively). Finally, within discordant twins, lateral ventricles were larger (14.4%) in patients than in their nonschizophrenic cotwins. CONCLUSIONS: Smaller intracranial volumes in the monozygotic patients and their cotwins suggest that increased genetic risk to develop schizophrenia is related to reduced brain growth early in life. The additional reduction in whole-brain volume found in the patients suggests that the manifestation of the disorder is related to (neurodegenerative) processes that are most likely nongenetic in origin.

Adult↗
PubMed2001

Focal gray matter density changes in schizophrenia.

BACKGROUND: The view that schizophrenia is a brain disease particularly involving decrements in gray matter is supported by findings from many imaging studies. However, it is unknown whether the (progressive) loss of tissue affects the brain globally or whether tissue loss is more prominent in some areas than in others. METHODS: Magnetic resonance whole brain images were acquired from 159 patients with schizophrenia or a schizophreniform disorder and 158 healthy subjects across a 55-year age span. Gray matter density maps were made and analyzed using voxel-based morphometry. RESULTS: Compared with healthy subjects, decreases in gray matter density were found in the left amygdala; left hippocampus; right supramarginal gyrus; thalamus; (orbito) frontal, (superior) temporal, occipitotemporal, precuneate, posterior cingulate, and insular cortices bilaterally in patients with schizophrenia or schizophreniform disorder. Compared with healthy subjects, increases in gray matter density were exclusively found in the right caudate and globus pallidus in patients with schizophrenia or schizophreniform disorder. A group-by-age interaction for density was found in the left amygdala, owing to a negative regression slope of gray matter density on age in the left amygdala in patients compared with healthy subjects. CONCLUSIONS: Gray matter density is decreased in distinct focal areas in the brains of patients with schizophrenia or schizophreniform disorder. The decreased density in the left amygdala is more pronounced in older patients with schizophrenia.

Adolescent↗
PubMed2001

Automated separation of gray and white matter from MR images of the human brain.

A simple automatic procedure for segmentation of gray and white matter in high resolution 1.5T T1-weighted MR human brain images was developed and validated. The algorithm is based on histogram shape analysis of MR images that were corrected for scanner nonuniformity. Calibration and validation was done on a set of 80 MR images of human brains. The automatic method's values for the gray and white matter volumes were compared with the values from thresholds set twice by the best three of six raters. The automatic procedure was shown to perform as good as the best rater, where the average result of the best three raters was taken as reference. The method was also compared with two other histogram-based threshold methods, which yielded comparable results. The conclusion of the study thus is that automated threshold based methods can separate gray and white matter from MR brain images as reliably as human raters using a thresholding procedure.

Adult↗