Oscar Albert Parsons - US grants

These cross-sectional and longitudinal studies examine CNS dysfunction and recovery in alcoholic men and women as manifested in a comprehensive battery of neuropsychological (NP) tests and 3 classes of evoked brain potentials (EP) at 3-weeks post-detoxification at 1-year posttreatment. Three major problem areas are addressed. 1) Patterns of NP and EP deficit at 3 weeks as functions of Gender and 2 background variables. a) Primary vs Secondary and b) Familial vs nonFamilial alcoholism. 2) Recovery of NP/EP functioning at 1 year in relation to Gender, the background variables and abstinence during the followup year. 3) Prediction of resumption of drinking during followup in relation to initial NP/EP deficits, Gender and the background variables. Data and relationships for reported childhood symptoms of hyperkinesis/minimal brain damage, alcohol consumption history, medical history and demographic variables will also be analyzed. Matched controls will participate both at initial testing and followup. The NP battery is composed of test clusters that assess 3 types of ability, Abstraction/Problem Solving, Learning/Memory and Perceptual-Motor Skills, each of which show impairment in alcoholic men and women. The EP battery employs 3 paradigms, auditory brainstem potentials, patterns reversal visual evoked potentials and event-related potentials (visual and auditory) elicited in information-processing contexts. Thus, we can assess the functional integrity of the primary auditory and visual input systems and of neural mechanisms that mediate aspects of selective attention and stimulus evaluation. All 3 paradigms have shown sensitivity to CNS dysfunctions in male alcoholics. These studies will extend previous research as follows: 1) Replicate our recent findings that the Primary-Secondary and Familial-nonFamilial background factors predict NP deficits in alcoholic men (Primary and Familial males show greatest deficit), extend these analyses to women and to the EP dependent variables, 2) define relationships between NP deficits and EP aberrations, in male and female alcoholics, 3) investigate in women the widespread EP aberrations found in male alcoholics, 4) determine reversibility of CNS dysfunctions with long term followup, 5) explicate the extent to which status on the background factors, gender and NP/EP deficits can predict resumption of drinking. This research will provide unique information on the roles of familial factors, etiology, and CNS dysfunctions in the course and recovery patterns in alcoholic men and women. The results should bear on the problems of interest to psychiatrists, psychologists, neurologists, rehabilitative workers and other disciplines in the field of alcoholism.

The existence of cognitive and preceptual-motor deficits have been repeatedly demonstrated in detoxified alcoholics. Three major issues require further consideration: 1) the neuropsychological model of deficit which best accounts for the data, 2) the extent to which recovery occurs with abstinence, and 3) the role of developmental factors in accounting for deficits in alcoholics. The neuropsychological model to be tested is that of generalized-diffuse dysfunction, which predicts that alcoholis will manifest at least mild impariment on the full range of cognitive and perceptual-motor functions. Male alcoholics will be given an extensive battery of neuropsychological tests, including tests of both verbal and nonverbal cognitive functioning and of perceptual motor abilities. Recovery from deficits will be evaluated by testing subjects 2 weeks, 6 weeks, 6 months and 1 year after initially stopping drinking. Interest drinking behavior will be assessed in order to examine the relationship between abstinence and recovery. The role of childhood hyperkinesis or minimal brain damage in accounting for deficits in alcoholics will be examined retrospectively by examining the frequency of reported symptoms of such disorders in alcoholics and controls. The effects of aging and alcohol abuse on cognitive functioning will be examined in separate groups of older (+60) alcoholics and social drinkers. The results of this project may have implications for all health professionals involved in the treatment of alcoholism. The investigation overlaps the fields of psychology, psychiatry and gerontology.

These cross-sectional and longitudinal studies examine CNS dysfunction and recovery in alcoholic men and women as manifested in a comprehensive battery of neuropsychological (NP) tests and 3 classes of evoked brain potentials (EP) at 3-weeks post-detoxification at 1-year posttreatment. Three major problem areas are addressed. 1) Patterns of NP and EP deficit at 3 weeks as functions of Gender and 2 background variables. a) Primary vs Secondary and b) Familial vs nonFamilial alcoholism. 2) Recovery of NP/EP functioning at 1 year in relation to Gender, the background variables and abstinence during the followup year. 3) Prediction of resumption of drinking during followup in relation to initial NP/EP deficits, Gender and the background variables. Data and relationships for reported childhood symptoms of hyperkinesis/minimal brain damage, alcohol consumption history, medical history and demographic variables will also be analyzed. Matched controls will participate both at initial testing and followup. The NP battery is composed of test clusters that assess 3 types of ability, Abstraction/Problem Solving, Learning/Memory and Perceptual-Motor Skills, each of which show impairment in alcoholic men and women. The EP battery employs 3 paradigms, auditory brainstem potentials, patterns reversal visual evoked potentials and event-related potentials (visual and auditory) elicited in information-processing contexts. Thus, we can assess the functional integrity of the primary auditory and visual input systems and of neural mechanisms that mediate aspects of selective attention and stimulus evaluation. All 3 paradigms have shown sensitivity to CNS dysfunctions in male alcoholics. These studies will extend previous research as follows: 1) Replicate our recent findings that the Primary-Secondary and Familial-nonFamilial background factors predict NP deficits in alcoholic men (Primary and Familial males show greatest deficit), extend these analyses to women and to the EP dependent variables, 2) define relationships between NP deficits and EP aberrations, in male and female alcoholics, 3) investigate in women the widespread EP aberrations found in male alcoholics, 4) determine reversibility of CNS dysfunctions with long term followup, 5) explicate the extent to which status on the background factors, gender and NP/EP deficits can predict resumption of drinking. This research will provide unique information on the roles of familial factors, etiology, and CNS dysfunctions in the course and recovery patterns in alcoholic men and women. The results should bear on the problems of interest to psychiatrists, psychologists, neurologists, rehabilitative workers and other disciplines in the field of alcoholism.

A good deal is known about the effects of both alcohol intoxication and sleep deprivation on human performance in specific tasks. However, little is known about the effects of these two treatment conditions of component cognitive processes, fundamental to a wide range of human activities. Further, little is known about the effects of these two conditions in combination, despite the fact that the two occur together commonly in a variety of social and industrial settings. Five factorial experiments have been designed to extend our knowledge of the independent and combined effects of alcohol and sleep deprivation on human cognitive processes and resources. The first three examine the effects of these treatments on component cognitive processes defined by categorically distinct task variables additive factors analysis of reaction times. The fourth examines the effects of the two treatments on response measures reflecting resource allocation. The fifth experiment will examine the mobilization of resources by incentive, which may ameliorate the effects of the two treatments. The first and last experiments also permit speed/accuracy analyses of performance, reflecting resource allocation and usage under the two treatment conditions. Integrated behavioral and event-related potential data will provide an account of alcohol and sleep deprivation effects on cognitive processes and resources required by a wide ranged of human activities. Such an account, based on component processes of human cognition, nay provide wider predictive generality than an account based on task-specific performance simulations alone.

Three studies are proposed which examine CNS dysfunction in family history positive and negative community alcoholic men and women, as manifested on neuropsychological (NP) tests and 3 classes of evoked brain potentials (EP) obtained 3 to 6 weeks post- detoxification. The NP tests measure verbal, abstracting/problem-solving, learning/memory and perceptual- motor functions. The EP paradigms, set within and information processing context, measure auditory and visual functional integrity and neural mechanisms that indicate aspects of selective attention and stimulus evaluation. Both NP & EP tasks have been shown previously to be sensitive to alcoholisms' effects. Seven major aims are addressed. The first two aims (Study A) are concerned with the 1) recovery of NP and EP functions at one- year post-treatment retest, 2) the prediction of recidivism from NP and EP variables, and changes in NP and EP performance as a function of background variables such as family history, severity of alcoholism, affective distress, childhood symptoms of attention deficit disorders and hyperactivity. Study B compares a male VA sample of alcoholics to our community males with the aims of 3) confirming the hypothesis that the VA sample will have more NP and EP deficits and 4) exploring a new dimension of family history analyses in which NP and EP performances will be compared in FH+ alcoholics with a father alcoholic vs. FH+ alcoholics where another primary relative is alcoholic vs. FH-alcoholics. Aim 5 investigates NP and EP differences in Cloningers' Type 1 and Type 2 alcoholics based on recent findings of our current study and the relationship of antisocial and depressive symptoms to Types 1 and 2 and to NP deficits. Aim 6) investigates the psychosocial correlates of FH+ and FH-alcoholics as a function of Type 1 and 2 membership. Study C has the major aim 7) of comparing a new sample of detoxified female alcoholics with our previous one and investigating the role of FH+, FH-, Type 1 and Type 2 in EP and NP performance as well as psychosocial correlates. The results of these proposed studies will be relevant to issues and questions surrounding NP and EP impairment in male and female alcoholics and the determinants of the individual differences with respect to the expression of these deficits. The results will be of interest to alcohol clinicians and researchers, psychologists, psychiatrists, rehabilitation specialists and other mental health workers.

The systematic assessment of drug effects in humans using combined measurement of cognitive functioning and brain electrophysiology is a powerful emergent technology. These methods have not been fully exploited in studies of the effects of diazepam or alcohol, two drugs which are commonly abused and often taken together. During this 5-year study of acute dose effects of diazepam and alcohol, jointly acquired behavioral and electrophysiological data will be used to: 1) determine the condition of afferent and efferent pathways, and the cognitive interface between them, 2) identify and localize impairments of specific information- processing operations within the cognitive reaction process, and 3) assess dose-related changes in performance strategies and in the management of cognitive resources. Speed loading and incentive variables will be used to test hypotheses about the mobilization and allocation of energetic resources. These experiments will result in a hierarchically integrated characterization of dose effects of diazepam and alcohol, independently and in combination, on cognition, sensory, motor and electrophysiological functioning in healthy young men. This will provide basic concepts, techniques and a comprehensive data base, with potential application to the systematic assessment of other benzodiazepines as well as other classes of drugs. The resulting account of the dose effects of diazepam and alcohol will fill major gaps in existing knowledge of the independent and combined effects of these drugs on information processing. The results will have predictive generality to the extent that stimulus input processing and response output processing are ubiquitous to most of the cognitive reaction processes invoked by the discrete performance demands encountered in daily human activities.

Two studies are proposed which examine CNS dysfunction in family history positive and negative community alcoholic men and women, as manifested on neuropsychological (NP) tests and in men, 3 classes of evoked brain potentials (EP) obtained 3 to 6 weeks postdetoxification. The NP tests measure verbal, abstracting/problem-solving, learning, memory and perceptual motor functions. The EP paradigms set within an information processing context, measure auditory and somatosensory functional integrity and neural mechanisms that index aspects of selective attention and stimulus evaluation. Study A compares a male VA sample of 126 alcoholics to our community alcoholic and nonalcoholic males with the aims of: 1) confirming the hypothesis that the VA sample will have more NP and EP deficits; and 2) exploring a new dimension of family history analyses in which NP and EP performances will be compared in FH+ alcoholics with a father alcoholic vs. FH+ alcoholics where another primary relative is alcoholic vs. FH alcoholics;3) investigation NP and EP differences in Cloninger's Type 1 an Type 2 alcoholics based on recent findings of our current study and the relationship of antisocial and depressive symptoms of Types 1 and 2 and NP deficits; 4) investigating the psychosocial correlates of FH+ and FH- alcoholics as a function of Type 1 and 2 membership; 5) investigating EP changes in alcoholics by using a somatosensory paradigm. Study B compares a new sample of 64 female alcoholics from community treatment programs to our current samples in order to: Aim 6) cross validate our current finding of NP performance deficits in Type 1 and "?Type 2" female alcoholics; Aim 8) investigate the medical and psychosocial differences in FH+ and FH alcoholics as a function of Type 1 and "?Type 2" alcoholics and Aim 9) determine whether there are deficits in female alcoholics interpersonal and "real life" impersonal problem solving and whether these deficits are predicted by our impersonal laboratory tests of problem-solving. New control samples of 24 community male and 20 females will also be tested to control for "Experimental Drift" and to increase the Ns of our present control groups. The results of these proposed studies will be relevant to issues and questions surrounding NP and EP impairment in male and female alcoholics and the determinants of the individual differences with respect to the expression of these deficits. The results will be of interest to alcohol clinicians and researchers, psychologists, psychiatrists, rehabilitation specialists and other mental health workers.

Memory deficits in alcoholics are a common clinical and research finding. The specific cognitive components of these deficits remain to be identified. A cognitive theoretical model, after Tariot and Weingarten, is proposed as a promising approach to the problem. This model postulates two memory stores. The first, episodic memory, is involved in the storage and use of contextually bound information. The second, knowledge memory, is involved in the storage and use of logic, meaning and structural relationships such as are involved in abstracting and problem-solving. Our model identifies three processes that characterize retrieval from the two stores: accessibility, availability and, what we term "efficiency." Thirteen studies are presented to address specific hypotheses and questions regarding possible alcoholics impairment within each of the processes for episodic memory (Exp. 1-6) and knowledge memory (Exp. 7-13). Measures of childhood and residual adult attention deficit disorders, family history of alcoholism, gender and stage of menstrual cycle in females are variables that will be examined for possible effects on differences in memory performance between alcoholics and controls. The project will be conducted in three phases. Phase 1-A, Episodic Memory, will use 48 alcoholics and 40 controls for Exps. 1, 2, and 6. Phase 1-B will use new samples of 48 alcoholics and 40 controls to perform Exps. 7- 13. All samples will be balanced for gender and family history of alcoholism. Alcoholics will be recruited from treatment programs in the community and will be diagnosed by DSM-III-R or NCAA criteria. Controls will be recruited from community sources. All subjects will be screened for any medical or psychiatric condition (other than alcoholism) that could affect memory. Subjects will be tested in our laboratories and paid upon completion of the testing. Dependent variables for the various studies, include measures of accuracy, number and type of errors, reaction times and, in two experiments, electrophysiological measures associated with cognitive processes. The results will contribute to the scientific literature by using a specific cognitive model to identify quantitative and qualitative differences in memory functions between alcoholics and controls and by the consideration of the possible effects of attention, gender and family history of alcoholism variables in the results.