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Biomedical subjects

D L Braff

Publications and source records attributed to D L Braff.

At least 55 records · Page 3Linked to original sources
PubMed1998

Multiple site evaluation of P50 suppression among schizophrenia and normal comparison subjects.

Normally, when two brief, non-startling auditory stimuli are presented 500 ms apart, with long (e.g., 10 s) interpair intervals, the positive potential occurring approx. 50 ms after the first stimulus (P50) is relatively large, and the P50 to the second stimulus is smaller. In schizophrenia patients, however, the P50 to the second stimulus is larger than normal. In this study, 36 schizophrenia and 36 normal comparison subjects were tested in a two-click paradigm. Data were recorded from six electrode locations (F3, Fz, F4, C3, Cz, C4). The results support the hypothesis that schizophrenia patients have poor P50 suppression that is not an artifact of differential P50 wave morphology or differences in the number of usable trials between groups. In addition, the vertex location alone (Cz) was equal to, if not better than, any combination of sites for differentiating between groups. These results support the use of the Cz site alone in most investigations of P50 suppression deficits among schizophrenia spectrum patients. Further work investigating the neuropathological correlates of poor P50 suppression among schizophrenia patients by recording from multiple electrode locations, however, could be helpful.

Adult↗
PubMed1998

Transient versus sustained visual channels in the visual backward masking deficits of schizophrenia patients.

BACKGROUND: Schizophrenia patients have information-processing deficits that can be quantified using visual backward masking. The visual information processing system is divided functionally and structurally into transient and sustained visual channels. When visual stimuli are presented to a subject, the transient pathway detects the presence and location of the stimulus while the sustained pathway is involved in fine discrimination and identification of the stimulus. While independent subcortically, the transient and sustained visual channels converge cortically into the dorsal and ventral processing streams that assess spatial relationships and object recognition respectively. METHODS: To better understand the underlying mechanisms of the visual backward masking deficits, 16 schizophrenia patients and 17 comparison subjects were tested on two different visual backward masking paradigms that required either locating or identifying a target letter. RESULTS: Schizophrenia patients had visual backward masking deficits in a task that involved locating a target letter while there were no deficits in the task that involved identification of a target letter. CONCLUSIONS: The visual backward masking deficits of schizophrenia patients suggest impairment in the processing of spatial information. These deficits are discussed in the context of our current knowledge of visual information processing and the neuropathophysiology of schizophrenia.

Adult↗
PubMed1998

Poor P50 suppression among schizophrenia patients and their first-degree biological relatives.

OBJECTIVE: This study's goal was to replicate the finding that family members of schizophrenia patients show poor P50 suppression during a paired-click auditory evoked response paradigm. METHOD: The paired-click paradigm was used to test 44 schizophrenia patients, 60 of their clinically unaffected first-degree relatives, and 45 normal subjects. Two clicks (83 dB[A] over a 60-dB[A] white noise background) separated by 500 msec were presented 60 times to all subjects. P50 responses to the first and second clicks were selected from the digitally filtered data by using standard methods and the Cz recording site. RESULTS: The schizophrenia patients had smaller P50 responses to click 1 than either their relatives or the normal subjects; the patients and their relatives, who did not significantly differ, had larger P50 responses to click 2 than the normal subjects. Schizophrenia patients had worse P50 suppression than either their family members or the normal subjects; the patients' family members had worse P50 suppression than the normal subjects. CONCLUSIONS: Family members of schizophrenia patients have worse P50 suppression than normal subjects. To the authors' knowledge, this is the first demonstration independent of the group associated with the University of Colorado that schizophrenia patients' family members have poor P50 suppression. This result is intrinsically important, perhaps especially because a recent report suggests genetic linkage of poor P50 suppression to the cholinergic receptor's alpha7 nicotinic subunit.

Acoustic Stimulation↗
PubMed1997

Information processing deficits of schizophrenia patients: relationship to clinical ratings, gender and medication status.

Information processing deficits were explored in a large cohort of schizophrenia patients (N = 125) and non-psychiatric subjects (N = 52). Gender, medication status and symptom factors were assessed relative to measures of performance in critical stimulus duration (CSD), visual backward masking (VBM) and auditory reaction time (RT) paradigms. Schizophrenia patients exhibited significant impairments in measures of CSD, VBM and both RT speed and RT set. Females in both groups had inflated CSDs relative to males. Female schizophrenia patients showed slower RTs and elevated RT set scores, but comparable VBM performance, when compared to males. This gender difference was not observed in the non-psychiatric subjects. To test the hypothesis that impaired performance in the VBM and RT paradigms would be related to negative symptoms and thought disorder, regression analyses were performed using factor scores derived from a factor analysis of SANS and SAPS items that generated three symptom factors: negative, disorganized, and reality distortion. Significant variance in performance on VBM and RT measures was accounted for only by the negative symptom factor. We conclude that VBM and RT assess information processing deficits in schizophrenia patients that are more related to the negative versus positive or disorganized symptoms of schizophrenia. It is possible that VBM and RT share overlapping or interacting neural substrates.

Adult↗
PubMed1997

P50 suppression among schizophrenia and normal comparison subjects: a methodological analysis.

The present report investigated the relationship between P50 suppression and habituation among 20 schizophrenia and 20 normal comparison subjects. Subjects were presented with clicks delivered over headphones in a S1-S2 paradigm (clicks were separated by 500 msec; average intertrial interval was 8 sec). There were 60 total trials; the data were analyzed separately for the first and second 30 trials. The groups did not differ either on the number of usable trials or on the morphology of their P50 responses. Consistent with previous reports, schizophrenia patients demonstrated deficient P50 suppression. The overall suppression effect was not due to a group difference on S1 P50 amplitudes, but was associated with schizophrenia patients having smaller S1-S2 P50 amplitude difference scores than normal comparison subjects. Furthermore, the suppression effect appears to be more pronounced during the first than during the second block of trials. Thus, it may be important to evaluate changes in P50 responses over time among schizophrenia and normal comparison subjects.

Arousal↗
PubMed1997

Neuroanatomy of schizophrenia.

The articles that appear in this issue offer a framework of insights about the neuroanatomy of schizophrenia from three learned and creative perspectives. All three articles advance our understanding of schizophrenia from a single locus/specific "lesion" model to more advanced perspectives of neural circuit dysfunction models. Goldman-Rakic and Selemon review their own and others' work on structure-activity relationships of the frontal cortex and related working memory dysfunction. This important but sometimes cloudy and complex area is illuminated by their highly specific, informative research. Jones focuses on thalamic abnormalities hypothetically linked to abnormal oscillations in large arrays of cortical and thalamic neurons, a critically important concept in understanding the functional consequences of abnormal (thalamic) brain structure and function. Graybiel describes her interest in abnormal basal ganglia activity-dependent loops that may access the thalamus and set the tone of thalamo-cortical transmission. This view allows for us to understand the "upward" influences on basal ganglia function (and dysfunction) relevant to schizophrenia. These intriguing articles raise a number of issues that await increased data and continued integrating insights. These issues include the need for more information about (1) the developmental timing of lesions or dysfunctions; (2) the extent and regional distribution of abnormalities; (3) the relationship of brain dysfunction to clinical/cognitive abnormalities; and (4) the variable expression of brain abnormalities across the schizophrenia spectrum. These three articles and their authors are at the forefront of our expanding knowledge about the neuroanatomy of schizophrenia and how complex structural and functional deficits are expressed in individuals in the group of schizophrenias.

Brain↗
PubMed1996

The relationship of information-processing deficits and clinical symptoms in schizotypal personality disorder.

Individuals with schizotypal personality disorder (SPD) are thought to be phenotypically related to individuals with schizophrenia. This assumption is partially supported by the fact that SPD patients have deficits on biological markers similar to those found in schizophrenia. Visual backward masking (VBM) performance and critical stimulus duration (CSD), measures of information processing found to be abnormal in schizophrenia patients, were assessed in 14 SPD and 21 comparison subjects. There was no significant difference between groups in VBM performance; however; there were significant correlations between VBM deficits and the number of SPD symptoms, as well as elevated scores on the Ego. Impairment Index (EII). Additionally, there was a trend (p = 056) toward elevations in CSD in the SPD versus the comparison group and CSD inflation appears to be most prominent in individuals with a greater number of social deficit symptoms and elevated physical anhedonia scores. These findings suggest an important relationship between symptoms of SPD and neurophysiologic deficits.

Adult↗
PubMed1996

Positive symptoms of psychosis in posttraumatic stress disorder.

The possible presence of hallucinations and delusional thoughts in posttraumatic stress disorder (PTSD) was investigated. Other symptom clusters were also assessed in order to further clarify the nature of PTSD. Twenty combat veterans with PTSD were compared to 18 combat veterans without PTSD on symptom rating scales. The subjects with PTSD exhibited a greater degree of depression, anxiety, agitation, anhedonia, and positive symptoms of psychosis than the comparison group. Specifically, the PTSD group manifested increased hallucinations, delusions, and bizarre behavior. Some of these positive symptoms did not appear to be due to reexperiencing of the trauma. The groups were not significantly different on indices of mania, thought disorder, or inertia. The clinical and diagnostic implications of the results are discussed. A diagnosis of PTSD should be considered with patients who have positive symptoms in the absence of thought disorder.

Adult↗
PubMed1996

Latent inhibition in schizophrenia.

Latent inhibition (LI) refers to the retarded acquisition of a conditioned response that occurs if the subject being tested is first preexposed to the to-be-conditioned stimulus (CS) without the paired unconditioned stimulus (UCS). Because the 'irrelevance' of the to-be-conditioned stimulus is established during non-contingent preexposure, the slowed acquisition of the CS-UCS association is thought to reflect the process of overcoming this learned irrelevance. Latent inhibition has been reported to be diminished in acutely hospitalized schizophrenia patients. If acutely hospitalized schizophrenia patients are preexposed to the CS, they learn the association as fast as, and perhaps faster than, patients who are not preexposed to the CS. This finding has been interpreted as reflecting the inability of acute schizophrenia patients to ignore irrelevant stimuli. In this study, the LI paradigm was identical to the one used in previous reports of LI deficits in schizophrenia patients (Baruch et al., 1988). Latent inhibition was observed in normal control subjects (n = 73), including individuals identified as 'psychosis-prone' based on established screening criteria, and in anxiety (n = 19) and mood disorder (n = 13) patients. Learning scores (trials to criterion) in "acutely' hospitalized as well as "chronic' hospitalized schizophrenia patients (n = 45) were significantly elevated in both preexposed and non-preexposed subjects, compared to controls. Acute schizophrenia patients exhibited intact LI. Separate cohorts of acute and chronic schizophrenia patients (n = 23) and normal controls (n = 34) exhibited intact LI when tested in a new, easier-to-acquire computerized LI paradigm. These results fail to identify specific LI deficits in schizophrenia patients, and raise the possibility that previously observed LI deficits in schizophrenia patients may reflect, at least in part, performance deficits related to learning acquisition.

Acute Disease↗
PubMed1996

Backward versus forward visual masking deficits in schizophrenic patients: centrally, not peripherally, mediated?

OBJECTIVE: Schizophrenic patients have repeatedly demonstrated the inability to rapidly process information when tasks are timed or the processing load is relatively high. Schizophrenic patients show consistent deficits in the visual backward masking paradigm. In visual backward masking, an informational target stimulus is presented, followed after an interstimulus interval by a masking stimulus that interferes with or interrupts target identification. METHOD: In order to clarify whether the visual backward masking deficits of schizophrenic patients are indeed central rather than peripheral in origin, the authors compared visual backward masking to psychometrically matched visual forward masking performance in 35 normal comparison subjects and then 35 schizophrenic patients. In visual forward masking, the mask precedes the target, and visual forward masking mechanisms are felt to be more peripheral (retinal) than are visual backward masking mechanisms. RESULTS: For psychometrically matched forward and backward masking tasks, the schizophrenic patients had a selective and differential deficit in the backward masking condition. CONCLUSIONS: These results support the interpretation that the observed visual backward masking deficits of schizophrenic patients are centrally mediated.

Adult↗
PubMed1996

Use of methods from chaos theory to quantify a fundamental dysfunction in the behavioral organization of schizophrenic patients.

OBJECTIVE: This study aimed to quantify the complexity of behavioral sequences of patients with schizophrenia and comparison subjects by using methods from nonlinear dynamical systems theory. METHOD: A simple choice task consisting of predicting 500 random right or left appearances of a stimulus was used to obtain binary response sequences in 22 patients with schizophrenia and 16 comparison subjects. Dynamical entropy was measured and the fluctuation spectrum of local subsequence entropies calculated to quantify the degree of interdependency between consecutive responses of patients and comparison subjects. RESULTS: The response sequences generated by the schizophrenic patients exhibited a higher degree of interdependency than those of comparison subjects. Moreover, schizophrenic patients exhibited significantly less consistency in their response selection and ordering, characterized by a greater contribution of both highly perseverative and highly unpredictable subsequences of responses within a test session. CONCLUSIONS: The result of the biological abnormality underlying schizophrenia may not be a simple increase or decrease of neuropsychological or neurobiological functions. Instead, the observed abnormalities in behavioral patterns reflect a quantifiable dysregulation and disorganization of these functions.

Adult↗
PubMed1995

"Normal" personality correlates of sensorimotor, cognitive, and visuospatial gating.

Specific psychiatric disorders are characterized by impaired selective inhibition or "gating" of responses to sensory or cognitive information. Less is known about gating differences among normal individuals. We tested carefully screened controls in measures of central inhibition: prepulse inhibition (PPI) of startle, the Stroop test, and negative priming (NP). Subjects were defined as "normal" or "psychosis prone," based on theoretically and empirically derived MMPI criteria. Performance on all measures by "psychosis-prone" individuals suggested reduced sensorimotor gating and/or increased cognitive or visual interference. Performance was most impaired in individuals scoring highest on the MMPI Goldberg Index, which was originally designed to distinguish "psychotic" from "neurotic" inpatients. Inhibition in Stroop and NP was correlated across all subjects, but PPI was not correlated with other measures. Gender differences were noted in PPI (male > female), but not Stroop or NP. Performance deteriorated with age in Stroop and NP, but not PPI. The results are discussed as they relate to psychophysical and neural correlates of normal personality dimensions.

Adolescent↗
PubMed1995

Increased sensitivity to the sensorimotor gating-disruptive effects of apomorphine after lesions of medial prefrontal cortex or ventral hippocampus in adult rats.

Sensorimotor gating of the startle reflex is impaired in humans with schizophrenia and in rats after mesolimbic D2 dopamine receptor activation. The loss of startle gating after D2 activation in rats has been used as an animal model of impaired sensorimotor gating in schizophrenia, because the ability of antipsychotics to restore startle gating in D2-activated rats correlates significantly with antipsychotic clinical potency. Substantial evidence indicates that the pathophysiology of schizophrenia includes structural and functional deficits in prefrontal and temporal regions, particularly the dorsolateral prefrontal cortex and the hippocampus and parahippocampal gyrus. The present study assessed startle gating in adult rats after ibotenic acid lesions of the medial prefrontal cortex or ventral hippocampus. Medial prefrontal cortex lesioned rats exhibited normal startle amplitude and normal sensorimotor gating, as reflected by prepulse inhibition (PPI) of the startle reflex. Hippocampus lesioned rats exhibited elevated startle amplitude, and similar to rats with medial prefrontal cortex lesions, did not show significant changes in basal PPI. Low doses of the mixed dopamine agonist apomorphine did not significantly reduce PPI in sham lesioned rats, but significantly disrupted PPI in both medial prefrontal cortex- and ventral hippo-campus lesioned rats. These data are consistent with the hypothesis that cell damage in frontal and temporal cortex increases the sensitivity to the sensorimotor gating-disruptive effects of dopamine receptor activation.

Animals↗
PubMed1995

Neonatal excitotoxic hippocampal damage in rats causes post-pubertal changes in prepulse inhibition of startle and its disruption by apomorphine.

Neonatal excitotoxic hippocampal damage in the rat results in postpubertal onset of a variety of abnormal behaviors related to excessive dopaminergic transmission in the mesolimbic/nigrostriatal system, and thus may be considered an animal model of some aspects of schizophrenia. Because sensorimotor gating is impaired in adult patients with schizophrenia and in rats with experimentally induced mesolimbic dopamine hyperactivity, the present experiments investigated the effects of neonatal (postnatal day 7, PD7) ibotenic acid (3 micrograms) lesions of the ventral hippocampus (VH) on the amplitude and prepulse inhibition (PPI) of acoustic startle in prepubertal (PD35) and postpubertal (PD56) rats. Startle was elicited using 105 and 118-dB pulses alone or preceded by 4, 8, or 16 dB above-background prepulses in rats treated with vehicle or apomorphine (APO; 0.025 or 0.1 mg/kg SC). At PD35, PPI in VH-lesioned rats did not differ significantly from these measures in sham operated rats. Apomorphine significantly increased startle amplitude and reduced PPI in both sham operated and VH-lesioned rats at PD35. At PD56, startle amplitude in VH-lesioned rats was not significantly different from controls, but PPI was reduced significantly compared to controls. Ventral hippocampus lesioned rats also exhibited an exaggerated reduction in PPI after treatment with APO. These findings provide further evidence of postpubertal impairments that may be related to increased mesolimbic dopamine transmission and receptor sensitivity in rats with neonatal hippocampal damage, and provide further support for the fidelity of this animal model of schizophrenia.

Animals↗
PubMed1995

Gender differences in schizophrenia.

In an assessment of gender differences in schizophrenia, 85 outpatients (53 men and 32 women) with schizophrenia were evaluated for illness history, symptom severity, IQ, neurocognitive status, cerebral volume loss, and cortical asymmetry. Social functioning was assessed using marital status, independent living skills, and employment status. Significant gender differences were found, as women were on lower doses of neuroleptic medications and more frequently met criteria for paranoid and disorganized subtypes of schizophrenia than men. Women also were better educated and more often married, living independently, and employed. No gender differences were found in present age, symptom severity, neurocognitive functioning, or clinical magnetic resonance imaging scan readings. Our findings suggest that women may experience less of the adverse interpersonal psychosocial consequences of schizophrenia than men, even when symptom and neurocognitive status is equivalent between groups. However, more extensive investigations are warranted to better understand the role of pathophysiological or social mechanisms in gender differences.

Activities of Daily Living↗
PubMed1995

Impaired prepulse inhibition of acoustic and tactile startle response in patients with Huntington's disease.

The corpus striatum serves a critical function in inhibiting involuntary, intrusive movements. Striatal degeneration in Huntington's disease results in a loss of motor inhibition, manifested by abnormal involuntary choreiform movements. Sensorimotor inhibition, or "gating", can be measured in humans using the startle reflex: the startle reflex is normally inhibited when the startling stimulus is preceded 30-500 ms earlier by a weak prepulse. In the present study, prepulse inhibition (PPI) was measured in patients with Huntington's disease to quantify and characterise sensorimotor gating. Compared with age matched controls, patients with Huntington's disease exhibit less PPI. Startle gating deficits are evident in patients with Huntington's disease when startle is elicited by either acoustic or tactile stimuli. Even with stimuli that elicit maximal PPI in normal subjects, patients with Huntington's disease exhibit little or no PPI, and their pattern of startle gating does not show the normal modulatory effects usually elicited by changing the prepulse interval or intensity. Startle amplitude and habituation and latency facilitation are largely intact in these patients, although reflex latency is significantly slowed. In patients with Huntington's disease, startle reflex slowing correlates with cognitive impairment measured by the dementia rating scale, and with the performance disruptive effects of interference measured by the Stroop test. These findings document a profound disruption of sensorimotor gating in patients with Huntington's disease and are consistent with preclinical findings that identify the striatum and striatopallidal GABAergic efferent circuitry as critical substrates for sensorimotor gating of the startle reflex.

Acoustic Stimulation↗
PubMed1995

Gating and habituation deficits in the schizophrenia disorders.

Gating and habituation deficits have been identified as major features of the schizophrenias. When gating and habituation functions are impaired, the schizophrenia patient can neither efficiently screen out trivial, distracting stimuli nor effectively attend to and process salient stimuli in the environment. Along with the clinical significance and symptom correlates of gating and habituation deficits in schizophrenia, studies of these functions have produced much important data. Specifically, such studies have demonstrated the involvement of structures in the cortico-striato-pallido-pontine (CSPP) neural circuitry in both schizophrenia and the normal processing of information. Thus, neurobiological manipulations along various axes of the CSPP can allow investigators to understand the neural basis of impaired gating and habituation in the schizophrenias.

Acoustic Stimulation↗