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Biomedical subjects

A F Mirsky

Publications and source records attributed to A F Mirsky.

At least 55 records · Page 3Linked to original sources
PubMed1987

Effects of gamma-hydroxybutyrate on the performance of monkeys in a Go/No-go visual discrimination task.

It has been suggested that monkeys, administered gamma-hydroxybutyrate (GHB), manifest a state resembling petit mal status. This implies that an animal would produce erroneous responses immediately prior to, and discontinue behaviors requiring any cognitive effort concurrently with, an episode of GHB-induced generalized 3 cps wave-spike bursts in the EEG. This prediction was not confirmed in the present study. Rhesus macaques (Macaca mulatta) were trained to perform in a visual discrimination Go/No-go test. Thereafter bipolar transcortical electrodes were implanted in the hemisphere contralateral to the preferred hand. All monkeys discontinued to lever-press for water reward when administered GHB (125 or 250 mg/kg, esophageal intubation) and exhibited signs of reduced postural control and somnolence punctuated by episodes of hypermotility about 40-50 min after GHB. However, the monkey's difficulties in completing the program were not associated with the development of generalized hypersynchronous EEG activity. While occasional wave-spike bursts did occur, they were poorly regulated, often 'focal' (i.e. developed only in isolated areas), and had a frequency of 1.5-2 cps. In this state, animals could be easily roused by sensory stimuli. All of them reacted with a characteristic aversive-aggressive display when confronted by a direct gaze. These effects are interpreted to be more consistent with characterization of GHB activity as that of a potent hypnotic rather than a convulsant agent.

Animals↗
PubMed1987

Review of the NIMH Israeli Kibbutz-City Study and the Jerusalem Infant Development Study.

The National Institute of Mental Health (NIMH) Israeli Kibbutz-City Study has followed the development of offspring of schizophrenic parents from middle childhood through early adulthood. During childhood, a subgroup of offspring of schizophrenic patients showed clear neurobehavioral deficits often accompanied by poor social competence. Early followup data suggest that this subgroup of high-risk children is at greatest risk for adult schizophrenia spectrum illness. The Jerusalem Infant Development Study has followed a similar population of children at risk for schizophrenia from before birth through middle childhood. A subgroup of dysfunctioning in the high-risk children showed sensorimotor dysfunctioning in the first year of life, which was followed by perceptual, motor, and attentional dysfunctioning in childhood--identical to that found in the NIMH cohort. Results from both studies support the hypothesis that schizophrenic illness involves constitutional factors whose expression can be observed as early as infancy. Results also illustrate the importance of using data-analytic approaches that (1) look for subgroups within high-risk groups rather than only group differences between high- and low-risk groups, and (2) examine profiles of behavior rather than only single variables.

Adolescent↗
PubMed1987

Behavioral and psychophysiological markers of disordered attention.

Behavioral and psychophysiological assays provide the most sensitive indication of whether a presumed neurotoxin has a deleterious effect on the nervous system. The effects of lead on the nervous system are strongly suggestive that this agent can produce disturbances in attention; moreover, there are clinical reports of such effects. The action of lead is also manifest in behaviors described as "hyperactive," or reflecting "minimal brain damage." The core symptom in both disorders is probably impairment in attention. The recent Diagnostic and Statistical Manual (DSM-III) of the American Psychiatric Association uses the term Attention Deficit Disorder to replace such terms as hyperactivity and minimal brain damage. Prior studies of the behavioral toxicity of lead may have used inadequate or incomplete assays of attention; this could in part account for the variability in outcomes. Recent research on attention suggests that it is a complex behavior consisting of a number of elements or components, each of which may be in part dependent upon a different region of the central nervous system. Behavioral assays should examine the components of attentive behavior using tests which are sensitive to the different elements. It is recommended that psychophysiological assays (using cognitive event-related potentials), although more difficult and costly to implement, be used as well. These assays may provide a more dynamic view of altered information processing in the brain and help to localize and characterize the behavioral impairment.

Animals↗
PubMed1986

The Israeli High-Risk Study: reply to Kaffman.

Kaffman's critique (1986) of the Israeli High-Risk Study centers on a number of issues: research design, information reported, appropriateness of sample, and Kaffman's own direct experience with psychiatric populations in kibbutzim and elsewhere in Israel. I contend that Kaffman has not fully understood the goals, methods, design, or results of the investigation. The information reported was as complete as possible if it is borne in mind that many of the issues and problems he has raised were not considered in research done on psychiatric disorders 25 years ago. Nevertheless, I contend that the Israeli study meets currently accepted standards of psychiatric research, that the results are valid, and that they raise questions about possible pathogenic influences on vulnerable persons raised on kibbutzim.

Adolescent↗
PubMed1986

Petit mal epilepsy: a review and integration of recent information.

Petit mal (absence) epilepsy remains one of the most enigmatic of neurological disorders, and there is no widely accepted theory of its etiology. This review covers some of the current issues concerned with the disorder, including treatment and prognosis, neurochemical research, behavioral and psychophysiological effects of wave-spiked discharges, and EEG studies of seizure control. With respect to treatment, although effective drug therapy (valproic acid, ethosuximide) exists for the "pure" form of absence epilepsy, other forms, in which there is an admixture of grand mal seizures, are less amenable to pharmacotherapy. Moreover, the frequency of fatal hepatic toxicity following valproic acid therapy has been estimated at 1 in 20,000. With respect to prognosis, follow-up studies indicate that many patients do not outgrow the disorder but continue to suffer absence seizures well into adulthood. In recent years, there has been considerable research on the neurochemical basis of absence epilepsy. Current theories, including those that implicate gamma-aminobutyric acid, catecholamines, and "endogenous" epileptogens, are summarized; and requirements for an experimentally induced animal model of absence epilepsy are discussed. The majority of behavioral studies of the disorder have concerned the effects of petit mal-type discharges on sensory and cognitive processes. Some of these studies are reviewed; and recent work bearing on these issues, involving event-related brain potentials, is presented. Our review concludes with a discussion of research aimed at the development of electrophysiologically based approaches to the reduction of seizure frequency in patients with absence epilepsy.

Adolescent↗
PubMed1985

The NIMH-Israeli schizophrenia project: the history of a high-risk study.

We have reviewed some of the difficulties encountered in bringing this study to completion. Among our special problems were the necessity of collecting large numbers of measures on a relatively small study population, the need to recruit and maintain a staff over long periods of time, the wide geographical separation between staff members responsible for design and those responsible for execution of the study, and the difficulties of conducting longitudinal research in a politically unstable part of the world. Centralization of data and data analysis proved a crucial step in bringing the study to its present level of completion.

Child↗
PubMed1985

Adult outcomes of high-risk children: differential effects of town and kibbutz rearing.

We conducted a followup study 15 years after the initial examination of 46 of the Israeli children at risk for schizophrenia (index cases) and 44 of the control children. Thus, we were able to contact and examine 90 of the surviving 99 subjects of the investigation. Half of the subjects had grown up in the communal child-rearing setting of a kibbutz, and half had been raised by their own parents in cities in Israel. The kibbutz-index cases, at average age 25, show the highest incidence of psychiatric disorder. Environmental factors that may have led to this outcome are discussed.

Adult↗
PubMed1985

Introduction: the Israeli high-risk study.

The literature on theories of the etiology of schizophrenia (the "nature-nurture dilemma") is reviewed, and the rationale is explicated for a study comparing the development and outcome of kibbutz- and town-reared children of schizophrenic parents. Various possible outcomes of the kibbutz-rearing experience in vulnerable children are discussed. The research team and the time table are described.

Adaptation, Psychological↗
PubMed1984

The Genain Quadruplets 25 years later: a diagnostic and biochemical followup.

A biological and clinical followup of the Genain Quadruplets was initiated as a multilaboratory collaborative effort at the National Institute of Mental Health (NIMH). The quadruplets are 51-year-old monozygotic women previously studied with a battery of psychological and physiological tests 25 years ago at the NIMH. The present article (the first of a series of three) details the clinical history and course of the schizophrenic illness in each of the quadruplets and describes the biochemical measures determined. The findings of elevated urinary phenylethylamine excretion, decreased plasma dopamine-beta-hydroxylase activity, and increased alpha-adrenergic receptor concentrations in all quadruplets warrant further genetic studies.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1984

The Genain Quadruplets: psychological studies.

A series of behavioral studies is reported on the Genain Quadruplets. These monozygous women, all of whom have suffered or are suffering from schizophrenia, were studied previously at the National Institute of Mental Health (1955-1958) and were the subject of an extensive report by Rosenthal (1963). Although the Genains are genetically identical, the expression of the schizophrenic disorder is unequal among the quads, and this circumstance has led to speculation about the relative contributions of nature and nurture (or diathesis and stress in Rosenthal's terminology) in the development of this disease. Two goals were pursued in this investigation: one concerned a comparison of the status of the Genains in 1981 as compared with 1958; the other concerned whether data from the armamentarium of newer behavioral and neurobiological techniques invented and employed since 1958 might shed some light on the unequal expression of schizophrenia among the quadruplets. We conclude that the Genains are functioning about as well as they ever have in their adult lives, and scores on attentional tests show improvement as compared to 1958 measures. This is probably attributable to the medication (primarily neuroleptics) and other supportive treatments they have received over the years. With respect to the varying degrees of illness seen in the Genains, scrutiny of the biochemical, physiological, neuroradiological, immunogenetic, and behavioral test data leads to speculation that certain unique biochemical findings interacting with differing types and amounts of cerebral pathology constitute a major cause of the variable expression of the schizophrenic diathesis.

Antipsychotic Agents↗
PubMed1984

The Genain Quadruplets: electrophysiological, positron emission, and X-ray tomographic studies.

Four 51-year-old monozygotic quadruplets concordant for schizophrenia, originally studied at the National Institute of Mental Health 25 years ago, were restudied with topographic electroencephalography (EEG), evoked potentials (EPs), computed tomography (CT scans), polysomnographic sleep recordings, and positron emission tomography (PET) with 18F-2-deoxyglucose. EEG and EP findings were consistent with those from other groups of patients with schizophrenia and showed great similarity within the quadruplets. CT scans revealed uniformly small lateral ventricles. PET scans replicated earlier findings of relatively low glucose use in the frontal lobes but did not show strong familial concordance.

Brain↗
PubMed1983

The inheritance of schizophrenia spectrum disorders: a reanalysis of the Danish adoptee study data.

Rosenthal and colleagues earlier compared the frequency of schizophrenia spectrum disorders in two groups of persons adopted in infancy or early childhood: those with a psychotic parent (index group) and those whose biological parents had never had a psychiatric diagnosis or treatment (control group). They found significantly more disorder in the index group. Reanalysis of the original material using DSM-III and stricter exclusionary criteria applied to the parents yielded three times as many schizophrenia spectrum disorders in the index as in the control group. This difference remained statistically significant, supporting the operation of genetic factors in the transmission of the traits comprising the schizophrenic spectrum of disorders.

Adoption↗
PubMed1982

Prediction of spike-wave bursts in absence epilepsy by EEG power-spectrum signals.

The EEGs of subjects with absence seizures were examined to determine if changes occurred prior to spike-wave bursts that could be used to predict bursts. A number of 20-s epochs of EEG prior to spike-wave bursts (preburst epochs) and during periods remote from bursts (control epochs) were examined in 5 subjects. Power-spectrum analysis was carried out on each epoch and frequency bands from 0 to 50 c/s were combined into 2-c/s bandwidths. Logarithmically transformed power values in each frequency band were entered into a discriminant analysis algorithm for each subject separately. Results were expressed in terms of a test for significant differences between preburst and control epochs (F statistic) and a "success ratio" of discriminant analysis classification, defined as the proportion of correct classifications in both groups, as obtained using a cross-validation procedure. A significant preburst EEG pattern was found in 4 of the 5 subjects, and success ratios ranged from 0.64. to 0.83. Each subject's preburst EEG seemed to be characterized by a unique pattern of changes, and thus no common prodromal signal was found. The EEG changes did not appear to be caused by overt behaviors, such as eye closure or drowsiness. The findings suggest that the preburst EEG pattern represents a functional alteration in brain activity which could arise from the burst-producing mechanism directly.

Adolescent↗
PubMed1981

Clinical correlates of brainstem dysfunction in autistic children.

Children with the diagnosis of autism were tested for brainstem auditory evoked potentials (BAEP), and information was gathered on their medical and developmental histories and current developmental levels of symptomatology. On comparing the nine autistic children having abnormal BAEPs and the seven autistic children with normal BAEPs, the former were found to have exhibited greater pathology in the areas of attention and social accessibility. No differences were found between the groups on measures of language, motor, or perceptual functioning, or on previous diagnoses or medical history. It is suggested that social attentional pathology may be more specifically associated with the brainstem pathology that may characterize autism than are symptoms in other developmental areas.

Adolescent↗
PubMed1980

Prolonged brainstem transmission time in autism.

Brainstem auditory evoked potentials (BAEPs) to clicks presented monaurally were gathered for 16 institutionalized children with a prior diagnosis of autism and with no hearing loss as tested by standard audiometry. Twenty age-matched normal children served as controls. Brainstem transmission time, defined as BAEP interpeak I-V latency, was prolonged significantly on the average in the autistic sample on both left and right sides. Individually, BAEPs for 9 of the 16 autistic children (or 56%) on whom some electrophysiological data were gathered were classified as abnormal when compared to the norms established in the control group. The most common BAEP abnormality was a prolonged interpeak III-V latency on the left side.

Adolescent↗