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D L Braff

Publications and source records attributed to D L Braff.

At least 73 records · Page 4Linked to original sources
PubMed1994

Assessing the validity of an animal model of deficient sensorimotor gating in schizophrenic patients.

Psychiatric researchers need specific animal models to better understand the neurobiology of schizophrenia. Prepulse inhibition (PPI), the reduction in startle produced by a prepulse stimulus, is diminished in schizophrenic patients. Theoretically, deficient PPI in schizophrenic patients reflects a loss of sensorimotor gating that may lead to sensory flooding and cognitive fragmentation. In rats, PPI is disrupted by systemic administration of dopamine agonists or by manipulations of neural circuitry linking the limbic cortex, striatum, pallidum, and pontine reticular formation. This loss of PPI in rats may be a useful model for studying the neurobiology of impaired sensorimotor gating in schizophrenic patients. We assessed the face, predictive, and construct validity of this animal model. Face validity was supported: stimulus manipulations produced parallel changes in PPI in humans and rats, and the dopamine agonist apomorphine disrupted PPI in rats, mimicking PPI deficits in schizophrenics. Predictive validity was supported: the ability of antipsychotics to restore PPI in apomorphine-treated rats correlated with clinical antipsychotic potency (rs = .991) and D2-receptor affinity (rs = .893). Antipsychotics that restore PPI in apomorphine-treated rats include "typical" antipsychotics and the "atypical" antipsychotic clozapine. Construct validity was supported: PPI was disrupted in rats when dopamine was infused into the nucleus accumbens; this effect was blocked by haloperidol. The loss of PPI in dopamine-activated rats may be a valid animal model of sensorimotor gating deficits in schizophrenic patients. This model may help us understand the neurobiology of cognitive deficits in schizophrenic patients.

Acoustic Stimulation↗
PubMed1994

The assessment of sequential response organization in schizophrenic and control subjects.

1. A novel analysis is introduced for the sequential organization of behavioral elements derived from the ergodic theory of nonlinear dynamical systems and statistical mechanics of physical systems. 2. This analysis yields the fluctuation spectrum of local dynamical entropies, S (h), which quantifies the contributions of subsequences with different degrees of association between elements to the overall observed behavior. In addition, q-dependent order parameter functions assess the relationship between the degree of association between consecutive behavioral elements and qualitative aspects of the subsequences. 3. A binary choice task paradigm is used to extract thought-contingent responses in order to determine the organization of sequences of behavioral actions. 4. A group a schizophrenic patients and controls was tested with a binary choice task paradigm to determine the sequential organization of their responses. 5. The results indicate that the overall response sequences of both schizophrenics and controls are non-random. In addition, clear differences in qualitative aspects between response subsequences with different degrees of association are revealed. Finally, significant fluctuations within individual subjects were found between highly predictable and highly unpredictable response subsequences. 6. These results are discussed with respect to dysregulations in behavioral organization that could not be assessed previously and may provide new insights into the behavioral effects of the underlying dysregulated neural circuitry.

Adult↗
PubMed1994

Information-processing deficits and thought disorder in schizophrenia.

OBJECTIVE: The goal of this investigation was to study the relationship between information-processing deficits and thought disorder in schizophrenic patients. METHOD: Fifty-two subjects diagnosed with schizophrenia were administered tests of information processing and thought disorder. The information-processing tests included visual backward masking and prepulse inhibition of the startle reflex. Thought disorder was measured with the Magical Ideation Scale, the Scale for the Assessment of Positive Symptoms, the alogia subscale of the Scale for the Assessment of Negative Symptoms, and the Ego Impairment Index-human experience variable and its subcomponents derived from the Rorschach. RESULTS: Elevated poor responses on the Ego Impairment Index-human experience variable were significantly correlated with information-processing deficits. In a simultaneous multiple regression, the auditory prepulse inhibition measure was the best predictor of poor responses on the Ego Impairment Index-human experience variable. CONCLUSIONS: The results suggest a correlative relationship between information-processing deficits and thought disorder. The relationship is most apparent when highly sensitive measures of both information processing and thought disorder are used. Furthermore, the prediction of poor responses on the Ego Impairment Index-human experience variable by auditory prepulse inhibition is important, since the neural circuitry of prepulse inhibition is known and involves the modulatory influences of the cortical-striatal-pallidal-thalamic circuit. These findings lend support to the hypothesis that information-processing failures are associated with cognitive fragmentation and thought disorder. More speculatively, these results allow us to hypothesize that impairments in part of the cortical-striatal-pallidal-thalamic circuit may lead to thought disorder, as well as prepulse inhibition deficits.

Adult↗
PubMed1993

Men are more inhibited than women by weak prepulses.

The acoustic startle reflex is normally inhibited when the startling stimulus is preceded by a weak prepulse. We studied "prepulse inhibition" (PPI) to assess potential gender differences in this operational measure of sensorimotor gating. A review of data from our previously published studies in psychiatric patients and normal controls indicated that startle in women was less inhibited by weak prepulses than was startle in men, and that this gender difference narrowed when stronger prepulses were used to elicit maximal levels of PPI. Based on these observations, new subjects were selected for study using our established criteria to exclude individuals with psychiatric disorders, substance abuse, or serious neurologic or medical illness. Replicating our preliminary observation, women exhibited significantly less PPI than men, with the gender difference being most notable under conditions with weak prepulses. Potentially confounding variables, including electrode impedance, startle amplitude, habituation and latency did not differ between men and women. PPI was then measured in male and female rats, where no gender differences were noted. These findings identify significant gender differences in PPI in humans, and suggest that inhibitory "gating" processes are more robust in men than in women, when assessed using a sensitive range of inhibitory stimuli.

Acoustic Stimulation↗
PubMed1993

Information processing and attention dysfunctions in schizophrenia.

Abnormalities of information processing have played a central role in understanding schizophrenia since the time of Kraepelin and Bleuler. Clearly, schizophrenia spectrum patients have profound problems focusing attention on salient cues and overcoming the disrupting effects of distracting stimuli. Theoretically, such patients are rendered vulnerable to stimulus inundation, cognitive fragmentation, and thought disorder induced by this inability to adequately process self-generated cognitive cues and stimuli from the complex world that surrounds us. Adding to the strength of such theories, investigators have made considerable progress in clarifying the functional significance and neurobiological basis of information-processing/attentional dysfunctions. This article focuses on our understanding of information-processing/attentional dysfunctions in schizophrenia. The relevant material will be presented in four parts: (1) an overview; (2) a review of specific, conceptual issues in information-processing research of the group of schizophrenias, including the roles of antipsychotic medications and generalized versus specific deficits; (3) a review of 10 common techniques used to tap the information processing and attention dysfunctions of schizophrenia patients; recent advances and novel applications of these techniques in "boundary" populations such as high-risk children and schizotypal patients are discussed and psychopharmacological probes, animal models, and basic strategies are also reviewed; and (4) an integration and suggestions for future directions in information-processing/attention research in schizophrenia. Overall, information-processing research provides an important viewpoint from which we can understand the group of schizophrenias.

Attention↗
PubMed1993

Sensory gating and inhibitory function in late-life schizophrenia.

Although similarities between the cognitive deficits observed in schizophrenia and those observed in aging have been recognized for over 50 years, little work has been done to directly examine these similarities or their implications for late-life schizophrenia. We review studies of prepulse inhibition, habituation, latent inhibition, and negative priming that indicate marked similarities in the patterns of deficits observed in schizophrenia and in aging. We also present new data from preliminary studies of prepulse inhibition and negative priming in which we compare young normal controls, older adult normal controls, and late-life schizophrenia patients. For both measures, both schizophrenia patients and older adults showed an inhibitory deficit relative to young controls. In the case of negative priming, older schizophrenia patients showed evidence of greater inhibitory dysfunction than did normal older adults, suggesting that older schizophrenia patients suffer a deficit resulting from the combined effects of schizophrenia and aging. The implications of these results and directions for future research are discussed.

Acoustic Stimulation↗
PubMed1993

Impaired startle prepulse inhibition and habituation in patients with schizotypal personality disorder.

OBJECTIVE: Information processing measures that serve as biological markers for schizophrenia can help to define the boundaries of schizophrenia. Prepulse inhibition and habituation of the blink reflex component of startle, which are thought to reflect an individual's ability to screen out or "gate" irrelevant sensory stimuli, are impaired in patients with schizophrenia. These deficits in sensorimotor gating and habituation in schizophrenic patients may lead to sensory overload and, secondarily, cognitive fragmentation, disorganization, and thought disorder. The goal of this study was to test two hypotheses: 1) patients with schizotypal personality disorder would show a loss of sensorimotor gating reflected by impaired prepulse inhibition of the human startle response and 2) patients with schizotypal personality disorder would show deficits in startle habituation consistent with the deficits seen in patients with schizophrenia. METHOD: Prepulse inhibition and habituation were assessed in 12 men and four women who met DSM-III-R criteria for schizotypal personality disorder and in 22 normal comparison subjects. RESULTS: Patients with schizotypal personality disorder had deficits in acoustic prepulse inhibition and habituation similar to the deficits observed in patients with schizophrenia. Although there were no differences between patients with schizotypal personality disorder and normal subjects in latency from acoustic startle stimuli to response, latency facilitation was produced by the prepulse in both groups. CONCLUSIONS: This pattern of changes in amplitude and latency of the startle response suggests that subjects with schizotypal personality disorder perceive the prepulse stimuli but still demonstrate deficient sensorimotor gating of amplitude. These findings support the importance of startle prepulse inhibition and startle habituation as biological markers for schizophrenia spectrum disorders.

Acoustic Stimulation↗
PubMed1993

The abnormality of normal comparison groups: the identification of psychosis proneness and substance abuse in putatively normal research subjects.

OBJECTIVE: Careful assessment of research subjects is important because the inclusion of subjects who manifest psychopathology and significant substance abuse in normal comparison groups will decrease statistical and experimental power. The current study evaluated the usefulness of an MMPI-derived algorithm in identifying tendencies toward psychosis and substance abuse in putatively normal research volunteers. METHOD: Ninety-eight adults who were recruited as normal comparison research subjects completed the MMPI, psychiatric interviews, questionnaires, and selected neuropsychological tests. The MMPI classified 81 presumed normal subjects into four subgroups: 1) not psychosis prone/substance abuse not likely, 2) not psychosis prone/substance abuse likely, 3) psychosis prone/substance abuse not likely, and 4) psychosis prone/substance abuse likely. RESULTS: The MMPI psychosis-prone and substance abuse factors identified significantly distressed and dysfunctional individuals with a relatively high degree of accuracy. CONCLUSIONS: It is becoming increasingly apparent that the cursory self-report screening of normal subjects may result in unacceptable levels of psychopathology in comparison groups. The current results also indicate that an adequate substance abuse evaluation is extremely important and that brief self-report information may be misleading. Empirically derived assessment tools, such as the MMPI, may prove useful in allowing researchers to more accurately define control parameters and group membership.

Adult↗
PubMed1992

Gating and habituation of the startle reflex in schizophrenic patients.

Schizophrenic patients exhibit impairments in both sensorimotor gating and habituation in a number of paradigms. Through human and animal model research, these fundamental cognitive deficits have well-described neurobiologic bases and offer insights into the neuroanatomic and neurotransmitter abnormalities that characterize patients with schizophrenic spectrum disorders. In this context, the startle response is particularly interesting, because it is a cross-species response to strong stimuli that is plastic or alterable using experimental and neurobiologic manipulations. Thirty-nine medicated schizophrenic patients and 37 normal control subjects were studied in a new electromyography based startle response paradigm in which both prepulse inhibition (an operational measure of sensorimotor gating) and habituation (the normal decrease in response magnitude to repeated stimuli over time) can be separated and assessed in one test session. The results indicate that schizophrenic patients have extensive deficits in both intramodal and cross-modal sensorimotor gating and a trend to show acoustic startle habituation deficits. The deficit in prepulse inhibition of startle amplitude exhibited by schizophrenic patients was evident when an acoustic prepulse stimulus preceded either an acoustic or a tactile startle stimulus. No deficit was observed in the prepulse-induced facilitation of startle latencies, indicating that the failure of gating was not due to a failure of stimulus detection. These findings suggest centrally mediated deficits in sensorimotor gating in schizophrenic patients.

Acoustic Stimulation↗
PubMed1992

Wisconsin Card Sorting Test deficits in chronic paranoid schizophrenia. Evidence for a relatively discrete subgroup?

Some, although not all, researchers have reported dramatically increased numbers of perseverative responses on the Wisconsin Card Sorting Test (WCST) in schizophrenic patients compared to normal comparison subjects. The current study was designed to further explore the nature of possible WCST deficits in a group of paranoid schizophrenic patients compared to normal and psychiatric comparison subjects. In the current study, schizophrenic patients had significantly greater numbers of perserverative responses on the WCST than the comparison groups. The sample of patients with schizophrenia appeared to be characterized by a non-Gaussian distribution of perseverative responses on the WCST. WCST-impaired and WCST-nonimpaired schizophrenic subgroups were compared on cognitive and symptom measures, and increased perseverative responding was associated with negative symptoms, slowed reaction time, and more hospitalizations. While additional research is necessary to further investigate hypotheses of frontal versus generalized brain dysfunction in schizophrenic patients, WCST impairment seems to be present in a clinically meaningful subgroup of paranoid schizophrenic patients.

Adult↗
PubMed1992

Reply to cognitive therapy and schizophrenia.

These interesting articles on cognitive deficits and rehabilitation in schizophrenic patients stimulate many questions, two of which are discussed in this reply. First, it seems likely that skepticism regarding the utilization and efficacy of cognitive rehabilitation strategies is born of despair that these treatments will ever be funded and delivered. This unfortunate state of affairs can only be corrected by effective social and political lobbying for adequate funding for mental health care. Second, the traditional tension between allocation and stage models of attention/information-processing deficits in schizophrenic patients may now be resolved by emerging theories that creatively integrate elements of stage and allocation theories. As we test these integrated theories, old "distinctions" seem to disappear and a clearer picture of information-processing dysfunctions in schizophrenic patients is emerging.

Brain Injuries↗
PubMed1992

Negative symptomatology in schizophrenic outpatients.

This study examines the prevalence of negative symptoms, and assesses the convergence of negative and depressive symptoms in 60 chronically ill schizophrenic outpatients. Negative symptoms were assessed with the Scale for the Assessment of Negative Symptoms and the negative symptom cluster of the Brief Psychiatric Rating Scale (BPRS). Depressive symptoms were assessed with the depression subscale of the Brief Symptom Inventory and the depressive symptom cluster of the BPRS. A majority of patients in this group of relatively stable, schizophrenic outpatients demonstrated mild to moderate degrees of both negative and depressive symptoms. Correlations were not significant between negative symptom and depressive symptom measures, which suggests that the symptom constructs are relatively independent. Comparisons between a subgroup with prominent negative symptoms (N = 18) and a subgroup with minimal negative symptoms (N = 32) also revealed no significant group differences in variables that characterize clinical course (i.e., age of onset and frequency and duration of hospitalization) or in the severity of depressive symptoms. This lack of any significant differences on the clinical course variables may be partially explained by the heterogeneity of negative symptoms. The constellation of negative symptoms may differ not only in etiology but also in their temporal relationships to other aspects of the patient's clinical course. Longitudinal studies will be needed to track the long-term outcome of negative and depressive symptoms.

Adolescent↗
PubMed1992

Sensory gating deficits in schizophrenia: new results.

OBJECTIVE: It has been widely hypothesized that sensory gating failures and sensory overload occur in schizophrenic patients compared to normal subjects. The authors of this study sought to confirm and extend results of earlier studies that showed specific sensory gating deficits in schizophrenic patients. METHOD: Age- and sex-matched schizophrenic patients (N = 20) and normal subjects (N = 20) were tested using electrophysiologically recorded P50 event-related potentials to assess the overall competence of the subjects' central sensory inhibitory capacity by measuring sensory filtering or gating. P50 area responses to two 75-dB (conditioning and test) click stimuli of 0.04-msec duration, averaged over 60 trials, were recorded for each subject. Normally, the first (conditioning) click stimulus induces gating mechanisms that result in diminished or gated P50 event-related potentials in response to the second click stimulus. RESULTS: The schizophrenic subjects manifested a significant sensory gating deficit at frontal, central, and parietal electrode placement sites, with a nonsignificant tendency for the deficit to be most prominent in the frontal areas of the brain. CONCLUSIONS: These data reflect a regionally diffuse loss of normal sensory gating in schizophrenic patients.

Acoustic Stimulation↗
PubMed1991

Magnetic resonance imaging abnormalities in lenticular nuclei and cerebral cortex in schizophrenia.

Neuropathologic and brain imaging studies have produced evidence of brain abnormalities in schizophrenic patients, often within the cerebrum's limbic lobe, and, less frequently, within basal ganglia. In the present study we used magnetic resonance imaging morphometric techniques to estimate volumes of specific cerebral structures in schizophrenic patients and age- and sex-matched normal controls. Estimates of the volume of mesial temporal lobe structures were reduced and estimates of the volume of the lenticular nucleus were increased in the schizophrenic patients. There was also evidence of reduced cranial volume in some schizophrenics. The magnitude of the lenticular abnormality, but not the temporal lobe abnormality, was associated with age at first psychiatric contact; earlier onset was associated with larger lenticular nuclei. The possible relevance of these results to neurodevelopmental hypotheses about the pathogenesis of schizophrenia is discussed.

Adolescent↗
PubMed1991

The generalized pattern of neuropsychological deficits in outpatients with chronic schizophrenia with heterogeneous Wisconsin Card Sorting Test results.

Forty schizophrenic outpatients and 40 normal subjects were assessed using extensive clinical (eg, Brief Psychiatric Rating Scale, Scale for the Assessment of Negative Symptoms and Scale for the Assessment of Positive Symptoms) and neuropsychological (extended Halstead-Reitan Battery) measures. The schizophrenic patients had multiple neuropsychological deficits on tests of complex conceptual reasoning, psychomotor speed, new learning and incidental memory, and both motor and sensory-perceptual abilities. Neuropsychological impairment correlated more strongly with negative than positive symptoms. Overall, the schizophrenic outpatients showed relatively modest increases in the number of perseverative responses on the Wisconsin Card Sorting Test of abstraction flexibility. A subgroup of these schizophrenic patients seemed to be particularly impaired on the Wisconsin Card Sorting Test. This pattern of results, in conjunction with previous studies, supports the idea that, while some schizophrenic patients may have fixed, frontally based dysfunctions, these dysfunctions may be most prominent, and even fixed, in deteriorated, kraepelinian patients. These data provide evidence for diffuse and far-reaching deficits in a majority of outpatients with chronic schizophrenia.

Adult↗
PubMed1991

Delusions: a review and integration.

Delusions are often prominent symptoms in schizophrenia and other psychiatric and neurologic disorders. Despite the central descriptive importance of delusions, there is a paucity of comprehensive reviews, theoretical formulations, and empirical evaluations in this area. Research and theoretical work pertinent to delusions are reviewed with particular emphasis on current findings in the neurobiological, cognitive, and information-processing literature. Research on delusional thought seen in various psychiatric disorders is reviewed and integrated with critical aspects of schizophrenia research. Consideration of three factors may help in understanding delusional thought processes. These factors are state-trait variables, perseverative thought, and cognitive functional integrity.

Delusions↗
PubMed1991

Effects of spiperone, raclopride, SCH 23390 and clozapine on apomorphine inhibition of sensorimotor gating of the startle response in the rat.

Previous work suggests that the dopamine agonist apomorphine decreases prepulse inhibition (PPI) of the acoustic startle response in rats. To better understand the dopamine substrates of this apomorphine response, we investigated the effects of four pharmacologically distinct dopamine antagonists on the apomorphine-induced loss of PPI. Apomorphine (0.5 mg/kg s.c.) markedly decreased PPI for all prepulse intervals tested. This effect of apomorphine on PPI was reversed by pretreatments with the D2 antagonists spiperone and raclopride but not by pretreatment with the D1 antagonist SCH 23390. The atypical antipsychotic clozapine exhibited an "inverted-U" shaped dose-response curve, reversing the apomorphine-induced loss of PPI at low doses but not at high doses. High doses of both SCH 23390 and clozapine decreased PPI independent of apomorphine treatment. The effects of apomorphine on baseline startle amplitude were also differentially modified by these drugs: apomorphine potentiated startle amplitude in spiperone- and raclopride-pretreated animals, but apomorphine decreased startle amplitude in animals pretreated with SCH 23390 or high doses of clozapine. Prepulse inhibition has been shown to be markedly impaired in humans with schizophrenia. Since our present findings suggest that the activation of D2 dopamine receptors is responsible for the loss of PPI in rats, overactivity of D2 dopamine receptors might also be a substrate for PPI deficits in schizophrenia.

Analysis of Variance↗