Biomedical subjects
Publications and source records attributed to D B Newlin.
Regional distribution of cerebral blood flow was assessed in 10 normal social drinkers following consumption of .75 g/kg alcohol and in a control session without alcohol. Alcohol increased blood flow in the gray matter in all brain areas except the left anterior area. The results are discussed in terms of the effect of alcohol on regional cerebral activation.
Research has suggested the presence of brain damage as a cause or concomitant of chronic schizophrenia. The most recent research in this area has been the identification of abnormalities in schizophrenia by computed tomographic (CT) scans. A study was done to investigate localized changes in CT scan density numbers in the brains of schizophrenic patients, as opposed to the brains in normal control subjects. Twenty-four normal subjects and 23 schizophrenic patients were tested with CT scans. Density measurements in each area of the brain (left, right, anterior and posterior) were compared to three separate CT scan levels. Of six measurements of anterior left-hemisphere density, it was found that five showed lower density in schizophrenic brains, as compared with normal brains. Of the remaining 18 measurements that evaluated other areas of the brain, only three differentiated between schizophrenic patients and normal subjects. The results support the hypothesis that there are primary structural deficits in some schizophrenic patients, and these deficits are centered in and around the anterior area of the left (dominant) hemisphere. The results also demonstrated further implications.
An exploratory study was performed concerning autonomic-central nervous system relationships in humans. Four groups of subjects were selected on the basis of two variables reflecting styles of central activity, hemisphericity (as measured by lateral eye movements) and facial expressivity. These groups were exposed to two stressor tasks. A marginally significant relationship was found between right hemisphericity and facial expressivity. Right hemisphericity subjects had higher heart rates. Highly expressive subjects and left hemisphericity subjects each tended to show larger autonomic responses to stress, and subjects in whom both characteristics were combined showed particularly heightened responsiveness. It was concluded that individual differences in central nervous system activation are related to autonomic arousal.
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The growing literature on hemispheric asymmetries in schizophrenic populations is critically reviewed. Studies of lateral asymmetries in schizophrenics are discussed which have employed a wide range of methodologies, including assessment of motor, sensory, electrophysiological, neuropsychological, and structural abnormalities. This literature is discussed in relation to two theoretical viewpoints, one emphasizing impaired functioning of the corpus callosum, and the other positing left hemisphere overactivation and dysfunction in schizophrenic populations. It is concluded that the hypothesis of impaired callosal function has not been adequately tested because of methodological problems, the most serious of which is the failure to show differential deficit. The hypothesis of left hemisphere abnormality has gained consistent support, although methodological problems were noted. This research suggests a structural locus for schizophrenic pathology which is consistent with the symptomatology of the disorder, and provides avenues for further research.
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The present study assessed the efficacy of pattern feedback for producing integrative and dissociative patterns of heart rate (HR) and respiration rate (RR). 60 uninformed subjects were assigned to six groups in which beat-by-beat feedback was contingent upon production of a specific pattern of increased ( ), decreased ( ), or unchanged (=) HR and RR during 11 feedback trials. Concomitant changes in respiratory volume and general activity (GA) were also recorded. Groups given feedback for HR and RR changes in the same directions (HR RR and HR RR ) ANd for changes in opposite directions (HR RR and HR RR ) were generally unable to produce the respective patterns, indicating that pattern feedback does not enable subjects to produce a wide range of HR-RR patterns. However, evidence of dissociation of HR and RR was obtained in the HR RR= and HR RR= groups in which HR changed significantly in the appropriate directions without significant changes in RR. These results are not consistent with the view that RR changes are necessary for HR control, although significant concomitant changes in respiratory volume and GA indicated that HR control was non-specific relative to these variables.
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Attention and learning problems among children exposed to opiates in utero have been previously reported but are difficult to interpret due to imprecise measurement and inadequate control of postnatal factors. In this study, we used a behavior-based measure of attention (continuous-performance tasks) and a physiological index of sustained attention (cardiac vagal tone) to measure more precisely the process of sustained attention. Boys, aged 7 to 12, exposed to opiates in utero, were compared to boys whose mothers began using illicit substances after the child's birth (environmental controls), and boys whose mothers were non-drug users. This three-group design was intended to isolate in utero effects from postnatal environmental influences. Vagal tone, a measure of heart-rate variability sensitive to vagal influences on the heart, was measured pre- and postbaseline and during the three tasks of the Gordon Diagnostic System (Delay, Vigilance, and Distractibility). Vagal tone has been found to be sensitive to changes in environmental demand for sustained attention in infants, school-age children, and adults. Results indicated that when distractors were added to the vigilance task (Distractibility task), opiate-exposed boys failed to suppress vagal tone compared to both control groups. However, both the opiate-exposed boys and the environmental controls made fewer correct responses than non-drug-exposed controls on this task. These results indicate that normal physiological responses to increased attentional demand may be impaired in boys exposed in utero to opiates in this age range. However, the poor Distractibility scores of both the opiate-exposed and environmental controls suggests an important role of environmental influences on attentional performance.
Alcohol cues elicited a conditioned autonomic response that was opposite in direction to the effect of alcohol. Normal male social drinkers given placebo following four alcohol conditioning sessions showed a compensatory response consisting of decreased pulse transit time, vasomotor activity, and finger temperature. This pilot research, supports the application of a classical conditioning model to human alcohol problems.
The classical conditioning model of drug tolerance makes a strong prediction of an antagonistic placebo response, or a placebo response that is opposite in direction to the effect of alcohol. In an initial experiment, 85 normal social drinkers consumed near beer (0% alcohol) while autonomic measures were recorded continuously. Subjects who reported mild intoxication (n = 11) showed a significant decrease in heart rate from predrinking baseline compared to subjects who did not report intoxication (n = 57). In a replication study with a suitable control group, subjects who received near beer and reported mild intoxication (n = 8) showed a significant heart rate and electrodermal response opposite in direction to the autonomic effects of alcohol compared to a control group that received a soft drink (n = 10). The antagonist placebo response challenges current conceptualizations of placebo responding, and has implications for classical conditioning theories of alcoholism.
Newlin's [Newlin D.B. Evolutionary game theory of tolerance and sensitization in substance abuse. Paper presented to the Research Society on Alcoholism, Hilton Head, SC, 1998] evolutionary game theory of addictive behavior specifies how evolutionarily stable strategies for survival and reproduction may lead to addiction. The game theory of multiple chemical sensitivity (MCS) assumes that: (1) the MCS patient responds to low-level toxicants as stressors or as direct threats to their survival and reproductive fitness, (2) this activates the cortico-mesolimbic dopamine system, (3) this system is a survival motivation center--not a 'reward center', (4) the subject emits a counter-response that is in the same direction as the naive response to the chemicals, (5) previously neutral stimuli associated with chemicals also trigger conditioned responses that mimic those to the chemicals, (6) these counter-responses further activate the dopaminergic survival motivation system, and (7) this produces a positive feedback loop that leads to strong neural sensitization in these structures and in behavior controlled by this system, despite a small initial response. Psychologically, the MCS patient with a sensitized cortico-mesolimbic dopamine system is behaving as though his/her survival is directly threatened by these chemicals. Non-MCS subjects have counter-responses opposite in direction to those of the chemicals and show tolerance. An autoshaping/sign-tracking model of this game is discussed. This evolutionary game makes several specific, testable predictions about differences between MCS subjects, non-MCS controls, and substance abusers in laboratory experiments, and between sensitized and nonsensitized animals.
Substance abuse, involving drugs such as cocaine, heroin, alcohol, marijuana, nicotine, barbiturates, etc., is by far by the most prevalent psychiatric disorder. Much has been learned about the abuse of these substances that may be useful to consider in designing and analyzing research concerning multiple chemical sensitivities (MCS). We review the central role of sensitization in this literature, including its definition, measurement, and expression in animals and human volunteers. Common factors among abused drugs, including sensitization, are discussed. Finally, empirical studies are delineated or proposed to test some of the notions presented in this paper.