Biomedical subjects

S D Forman

Publications and source records attributed to S D Forman.

12 recordsLinked to original sources

PubMed2001

Sensitivity of prefrontal cortex to changes in target probability: a functional MRI study.

Electrophysiological studies suggest sensitivity of the prefrontal cortex to changes in the probability of an event. The purpose of this study was to determine if subregions of the prefrontal cortex respond differentially to changes in target probabilities using functional magnetic resonance imaging (fMRI). Ten right-handed adults were scanned using a gradient-echo, echo planar imaging sequence during performance of an oddball paradigm. Subjects were instructed to respond to any letter but "X". The frequency of targets (i.e., any letter but X) varied across trials. The results showed that dorsal prefrontal regions were active during infrequent events and ventral prefrontal regions were active during frequent events. Further, we observed an inverse relation between the dorsal and ventral prefrontal regions such that when activity in dorsal prefrontal regions increased, activity in ventral prefrontal regions decreased, and vice versa. This finding may index competing cognitive processes or capacity limitations. Most importantly, these findings taken as a whole suggest that any simple theory of prefrontal cortex function must take into account the sensitivity of this region to changes in target probability.

Adolescent↗

PubMed2000

Factor structure of neurologic examination abnormalities in unmedicated schizophrenia.

The heterogeneity and uncertain significance of neurologic exam abnormalities in schizophrenia prompted us to evaluate their factor structure. We administered a modified version of the Neurological Evaluation Scale (NES) to 103 unmedicated patients with schizophrenia. Data were distilled by combining right- and left-side scores, and by eliminating superfluous, rarely abnormal and unreliable items from the analysis. Exploratory principal components analysis yielded four factors: repetitive motor tasks (fist-ring, fist-edge-palm, alternating fist-palm, dysdiadochokinesis); cognitive-perceptual tasks (memory, audiovisual integration, right-left orientation, face-hand test, rhythm tapping reproduction); balancing tasks (Romberg, tandem gait); and the palmomental reflex. Evaluation of the relationship between these factors and clinical and demographic variables revealed a robust correlation between the cognitive-perceptual factor and full-scale IQ score. This analysis is a step toward developing empirical subscales of a modified NES, which may provide insights into the nature of neurologic impairment in schizophrenia and may prove clinically useful.

Adult↗

PubMed2000

Neurologic examination abnormalities in schizophrenia with and without a history of alcoholism.

OBJECTIVE: The current investigation examines the impact of a past history of alcoholism on neurologic examination abnormalities in schizophrenia (SZ). BACKGROUND: Individuals with SZ have a high rate of comorbid alcohol use disorders (AUDs), but relatively little is known about the potential adverse consequences of alcoholism for neuropsychological and neurologic functioning in SZ. Recent evidence suggests consistent but subtle neurocognitive differences between groups, with more prominent differences in neurologic examination abnormalities. METHOD: Thirty-three male patients with SZ or SZ/AUDs were evaluated using a modified Neurologic Evaluation Scale (NES) and ratings for positive and negative symptoms. RESULTS: The SZ/AUD group exhibited a greater impairment in the Cognitive-Perceptual factor of the Neurologic Evaluation Scale. Greater impairment in the tandem-Romberg factor or in motor items was not found, nor were groups different based on positive or negative symptoms. CONCLUSIONS: A history of alcoholism in SZ is associated with greater overall neurologic impairment, particularly in the area of cognitive-perceptual dysfunction, an area often found to be impaired in patients with schizophrenia without alcoholism.

Adult↗

PubMed1998

Inter-rater reliability of the neurological examination in schizophrenia.

Neurological Examination Abnormalities (NEA) are prevalent in schizophrenia, but the significance of this is obscured by methodological problems. The Neurological Evaluation Scale (NES), the most widely used structured neurological examination in schizophrenia research, has had limited study of its inter-rater reliability (IRR). An augmented version of the NES was jointly administered (one examiner-rater and one observer-rater) by three pairs of psychiatrists to two populations of patients with idiopathic psychotic disorders. In addition to the ordinal and categorical data yielded by the original NES, continuous data were recorded in one of the series. Reliability analyses of our populations and a previously published study, reveal consistently adequate IRR in 12 of the 26 items assessed, and inconsistently adequate IRR in an additional 11. Consistent with studies using other NEA schedules, IRR was unacceptably low for some items that rely on subjective severity ratings. Certain rare abnormalities, which posed difficulties for the estimation of IRR, are probably not generally useful in the study of schizophrenia. Reliability estimates of continuous, ordinal and dichotomous data were comparable in most cases. We recommend that certain items from the NES be deleted, and that other studies of NEA in psychiatry follow similar procedures before undertaking further analyses.

Adolescent↗

PubMed1998

Simultaneous glutamate and perfusion fMRI responses to regional brain stimulation.

Functional magnetic resonance imaging (fMRI) rests on the assumption that regional brain activity is closely coupled to regional cerebral blood flow (rCBF) in vivo. To test the degree of coupling, cortical brain activity was locally stimulated in rats by reversed microdialysis infusion of picrotoxinin, alphagamma-aminobutyric acid-A antagonist. Before and during the first 30 minutes of infusion, simultaneous fMRI (rCBF) and neurochemical (interstitial glutamate concentration) measures of brain activity were highly correlated (r = 0.83). After 30 minutes of picrotoxinin-induced stimulation, glutamate levels decreased but rCBF remained elevated, suggesting that additional factors modulate the relationship between neuronal neurotransmitters and hemodynamics at these later stages.

Animals↗

PubMed1997

Estimating test-retest reliability in functional MR imaging. II: Application to motor and cognitive activation studies.

Functional magnetic resonance imaging (fMRI) using blood oxygenation contrast has rapidly spread into many application areas. In this paper, a new statistical model is used to evaluate the reliability of fMRI activation in a finger opposition motor paradigm for both within-session and between-session data and in a working memory paradigm for between-session data. A slice prescription procedure for between-session reproducibility is introduced. Estimates are made for the probabilities of correctly and falsely classifying voxels as active or inactive and receiver operator characteristic curves are generated. In the motor paradigm, estimated between-session reliability was found to be somewhat reduced relative to within-session reliability; however, this includes additional sources of variation and may not reflect intrinsically lower reliability. After matching false-positive classification probabilities, between-session reliability was found to be nearly identical for both motor and cognitive activation paradigms.

Brain↗

PubMed1997

Dissociating working memory from task difficulty in human prefrontal cortex.

A functional magnetic resonance imaging (fMRI) study was conducted to determine whether prefrontal cortex (PFC) increases activity in working memory (WM) tasks as a specific result of the demands placed on WM, or to other processes affected by the greater difficulty of such tasks. Increased activity in dorsolateral PFC (DLPFC) was observed during task conditions that placed demands on active maintenance (long retention interval) relative to control conditions matched for difficulty. Furthermore, the activity was sustained over the entire retention interval and did not increase when task difficulty was manipulated independently of WM requirements. This contrasted with the transient increases in activity observed in the anterior cingulate, and other regions of frontal cortex, in response to increased task difficulty but not WM demands. Thus, this study established a double-dissociation between regions responsive to WM versus task difficulty, indicating a specific involvement of DLPFC and related structures in WM function.

Adult↗

PubMed1997

Minimum criteria for reporting child abuse from health care settings.

We evaluated how consistently clinicians of two hospitals reported child abuse and neglect, and the utility of specific, operational criteria for assessing hospital clinicians' compliance with the child abuse reporting laws. To evaluate clinicians' compliance, we audited the medical records of 85 children who had been reported to a child protective service (CPS) agency by clinicians at either of two hospitals and who had been seen at that hospital at least once before the index report of abuse. The time elapsed from first hospital visit to index abuse report among the 85 children averaged 4.3 years. In the children's records, we identified 28 earlier reports to the CPS agency and four episodes that met criteria we developed but that had not been reported. Thus, application of specific criteria resulted in the finding that 28 (88 percent) of 32 suspected abuse episodes were actually reported to the CPS agency (95 percent confidence interval: 76 to 99 percent). In a second phase of the study, we compared the content of 45 reported episodes of child abuse (4) index reports and four earlier reports) to the criteria in order to evaluate their utility. Thirty-five episodes (78 percent) met one of the criteria. Review of the remaining 10 episodes led to the development of one new criterion. We conclude that, although it has been estimated that hospital personnel nationwide report to CPS agencies only 69 percent of the child abuse cases they identify, clinicians at the hospitals we studied reported 88 percent of documented episodes of suspected abuse. We also conclude that specific, operational criteria can help in the assessment of hospital clinicians' compliance with their obligation to report child abuse and neglect.

Child↗

PubMed1995

Improved assessment of significant activation in functional magnetic resonance imaging (fMRI): use of a cluster-size threshold.

The typical functional magnetic resonance (fMRI) study presents a formidable problem of multiple statistical comparisons (i.e., > 10,000 in a 128 x 128 image). To protect against false positives, investigators have typically relied on decreasing the per pixel false positive probability. This approach incurs an inevitable loss of power to detect statistically significant activity. An alternative approach, which relies on the assumption that areas of true neural activity will tend to stimulate signal changes over contiguous pixels, is presented. If one knows the probability distribution of such cluster sizes as a function of per pixel false positive probability, one can use cluster-size thresholds independently to reject false positives. Both Monte Carlo simulations and fMRI studies of human subjects have been used to verify that this approach can improve statistical power by as much as fivefold over techniques that rely solely on adjusting per pixel false positive probabilities.

Brain↗

PubMed1994

Cerebrospinal fluid corticotropin-releasing factor increases following haloperidol withdrawal in chronic schizophrenia.

Corticotropin-releasing factor (CRF), an endogenous neuropeptide, has been shown to coordinate endocrine, behavioral and autonomic responses to stress. However, while previous studies of cerebrospinal fluid (CSF) CRF in schizophrenia have not demonstrated significant differences compared to control groups, these studies have not examined the effects of symptom severity or antipsychotic medication. CSF CRF concentrations increased in 18 of 21 male schizophrenic (DSM-III-R) patients after maintenance haloperidol was replaced by placebo (P < 0.0001); there was also a trend for relatively greater increases in relapsers. CRF concentrations were not significantly related to severity of psychosis, depression, anxiety or negative symptoms. During haloperidol treatment, but not after medication withdrawal, worse childhood premorbid adjustment was associated with higher CSF CRF levels. Finally, in contrast to the positive correlation between CSF CRF and norepinephrine concentrations reported in depression, a negative trend was seen in this schizophrenic sample.

Adult↗

PubMed1993

Characteristics of repeat users of a psychiatric emergency service.

OBJECTIVE: Patients who visited a psychiatric emergency service were studied to determine whether repeat visitors, who consume a disproportionate share of services, could be identified by demographic and diagnostic characteristics. METHODS: Data were obtained from a semistructured diagnostic interview given to all 16,257 persons who made 29,214 visits to an urban psychiatric emergency service in Pittsburgh, Pennsylvania, from 1985 to 1989. Patients were categorized into four groups based on the number of visits in the five-year period. Patients in group 1 made a single visit, while those in group 2 averaged less than one visit per year; those in group 3 made one or two visits per year, and those in group 4, more than two visits per year. RESULTS: Groups 3 and 4 constituted 5.1 percent of the sample but made 27.1 percent of the total visits. Repeat users were significantly more likely to be male, younger, unmarried, unemployed, and nonwhite and to have diagnoses of schizophrenia, other psychotic disorders, and personality disorders. CONCLUSIONS: Repeat users of psychiatric emergency services appear to have demographic and diagnostic characteristics that may permit their early identification. For such patients, implementation of alternative management strategies, such as intensive case management, may reduce their use of services.

Adolescent↗

PubMed1986

Membrane-dependent coagulation reaction is independent of the concentration of phospholipid-bound substrate: fluid phase factor X regulates the extrinsic system.

Negatively charged phospholipids accelerate blood coagulation; one suggestion is that the binding of the gamma-carboxyglutamic acid-containing zymogens to these lipid surfaces increases their effective concentration as substrates. Alternatively, the charged phospholipids could enhance the direct interaction of substrate with the catalytic complex, which is localized at the membrane surface. We distinguished the alternatives by using prothrombin fragment 1 to compete with the substrate for membrane binding sites without interfering with the direct enzyme-substrate interaction. In a tissue factor-factor VIIa system containing neutral phospholipids (to which the substrate does not bind), prothrombin fragment 1 had no significant effect on factor X activation (Km, 877 +/- 111 nM and 791 +/- 103 nM, with and without prothrombin fragment 1, respectively). In contrast, in a system containing 30% phosphatidylserine, prothrombin fragment 1 displaced phospholipid-bound factor X, increasing the free factor X concentration and the reaction velocity in all 22 determinations. As the velocity increases correlated only with the free factor X concentration, we conclude that the free factor X concentration controls this reaction velocity. The Km in the 30% phosphatidylserine system, calculated using free factor X concentration, was 41 +/- 5 nM and 63 +/- 9 nM, with and without prothrombin fragment 1, respectively. Thus, the negatively charged lipids decreased the intrinsic Km by over 90%. The methodology employed should be applicable to ligand-receptor systems in which ligand binds nonspecifically to the membrane surface.

Animals↗