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Biomedical subjects

R I Herning

Publications and source records attributed to R I Herning.

At least 19 recordsLinked to original sources

Cocaine dependence. A clinical syndrome requiring neuroprotection.

Cocaine use has increased the frequency of medical complications among younger individuals. Neurological and neurovascular complications include strokes, seizures, transient ischemic attacks, and headaches. Subclinical deficits in cerebral perfusion and EEG have been noted in this population. Although these subclinical deficits may be an indication of increased risk of medical complications, the prophalactic treatment of cocaine abusers with neuroprotective agents has not yet been advocated. Blood flow of the anterior and medial cerebral arteries was measured by transcranial Doppler sonography in cocaine abusers (n = 70) and control subjects (n = 20) to determine whether cocaine abusers might have reduced cerebral blood flow in large cerebral arteries. Blood flow was measured within three days of and again about 28 days after admission of subjects to an inpatient research ward to determine whether blood flow improved with monitored abstinence. The mean, systolic, and diastolic velocities as well as the Pulsatility Index (PI) in both arteries differed between the control and cocaine abusers (p < 0.05). After about a month of abstinence, blood flow for the cocaine-dependent subjects increased. These preliminary findings suggest that blood flow is reduced in cocaine abusers and that there is a slight improvement with abstinence. Further research is needed to determine whether blood flow in abstinent cocaine abusers can be increased by pharmacological manipulations.

Adult

Subclinical neurological and neurovascular deficits in cocaine dependence. Gender and psychosocial considerations.

Neurological and neurovascular deficits were reported in cocaine abusers. In order to examine the contribution of cocaine use severity as well as other psychosocial factors to these deficits, we examined the following measures in a sample of cocaine abusers (n = 70): blood flow (transcranial Doppler sonography), and psychosocial measures (the Norbeck Social Support Questionnaire, the Symptom Check List 90R, the Beck Hopelessness Scale, and the Ellison Wellness Scale). Blood flow in the anterior and medial cerebral arteries was lower in the cocaine abusers than in the control subjects. Both cocaine use and psychosocial measures significantly predicted decreases in blood flow.

Adult

Neurophysiological signs of cocaine dependence: increased electroencephalogram beta during withdrawal.

To determine whether a central nervous system marker of cocaine dependence might exist, the resting electroencephalogram (EEG) of 33 drug-free, cocaine-dependent men (DSM-III-R criteria) was compared with two control groups [nondrug group (n = 10) and drug group who abused drugs, but were not cocaine dependent (n = 20)]. The EEG was recorded from eight sites after about 10 days of monitored abstinence (range 4-15 days) on a closed research ward for the drug-using individuals. The EEG was recorded for the nondrug control group as outpatients. The drug history was determined by the drug history questionnaire and a medical screening interview. The percent of EEG beta activity for the cocaine-dependent subjects was greater than that of both control groups (p < .05) as well as a normative database (HZI: Tarrytown, NY). The percent of EEG beta in frontal and central areas of the cocaine-dependent individuals was correlated with the frequency of cocaine use during the last 30 days. High levels of EEG beta may be a neurophysiological withdrawal sign in cocaine-dependent men.

Adult

The effects of nimodipine on the EEG of substance abusers.

Cocaine abusers have increased EEG beta and areas of reduced cortical blood flow. Since, nimodipine has neuroprotective effects and increases blood flow, we investigated the efficacy of single and multiple doses of the nimodipine in normalizing the EEG of substance abusers. Fourteen subjects received single (0, 30, 60 mg) and eleven received multiple daily (up to 150 mg in 12 hours) doses of nimodipine to determine whether this drug would increase EEG alpha and decrease beta in substance abusers. The EEG was recorded from eight scalp locations (F3, C3, P3, O1, F4, C4, P4 and O2) for three minutes during eyes closed, and eyes open conditions. Single and multiple doses of nimodipine produced significant increases in EEG alpha and decreases in EEG beta in the eyes open condition. Thus, nimodipine may have potential therapeutic implications in the treatment of cocaine dependence. Chronic nimodipine dosing in cocaine-dependent individuals is now needed to confirm its efficacy in the treatment of cocaine dependence.

Adult

Nimodipine improves information processing in substance abusers.

We examined whether nimodipine can improve information processing in healthy drug abusers using cognitive event-related potential (ERP) methodology. Placebo and 30- and 60-mg doses of nimodipine were administered on separate days in a random double-blind design to twelve male subjects, who used cocaine and/or opiates as well as alcohol and marijuana. The subjects performed the auditory rare event monitoring (AREM) task and the paired letter version of the visual continuous performance task (CPT) before oral drug administration as well as one and two hours after drug ingestion. The EEG was recorded from 7 scalp locations. The P3 component of the ERPs to the target stimulus was reduced with repeated testing on the placebo day. The 30-mg dose of nimodipine blocked the decrease in P3, which reflects stimulus evaluation in both tasks. Chronic administration of nimodipine may alleviate the cognitive deficits observed in substance abusers during abstinence and prevent treatment relapse.

Adult

Event-related potentials and alpha synchronization in preadolescent boys at risk for psychoactive substance use.

Numerous studies have evaluated event-related potentials (ERPs) as biological indicators of the liability for alcoholism. This study extends that approach by investigating ERPs in boys at risk for other substance use disorders. Prepubertal (10-12 years) sons of fathers diagnosed with psychoactive substance dependence (n = 28) were compared to matched sons of nonaffected fathers (n = 26) on an auditory ERP oddball task. Multivariate analyses of variance applied to peak amplitude and latency measures indicated small to moderate between-groups differences at midline or parietal sites: N2 and P3 amplitude; P2, N2, P3, and Nc latency. This replicated P3 amplitude findings in alcoholism-risk studies, though the effect size was moderate. Analysis of event-related alpha power indicated significantly longer latency of alpha synchronization and oscillations of desynchronization in boys at risk. The alpha power findings were statistically the more robust of the measures applied. The role of neurocognitive factors in determining liability for substance use disorders is discussed.

Alpha Rhythm

Lack of evidence for context-dependent cocaine-induced sensitization in humans: preliminary studies.

Cocaine-induced behavioral sensitization is the well-documented phenomenon where repeated doses of cocaine elicit increasingly greater effects on motoric activity in rats. Some observations suggest that behavioral sensitization may provide a model for understanding the mechanisms of drug-craving elicited by environmental triggers or cues. The process of fully validating such an animal model for its ability to detect effective anticraving medicines is a difficult and long-term undertaking. As a first step in that direction, we decided to determine if cocaine can produce conditioned behavioral sensitization in humans using a paradigm fairly similar to that used for rodents. Because humans do not react to cocaine with the pronounced motor activation observed in rodents, we measured a variety of end points, including blood pressure (BP), heart rate (HR), respiratory rate, pupil diameter, hormones (prolactin and cortisol), and subjective responses using the questionnaire for drug-related feelings (QDRF) and the EEG. To mimic the home and test cages used in rodent studies, two rooms were used: a small test chamber and a regular room with a window and furnishings. On day 1 each subject received a drug infusion (either saline or 40 mg cocaine IV) in both locations. On day 2, all subjects received an infusion (saline or 25 mg cocaine IV) in the test chamber. All drug infusions were conducted double blind. The paired group received cocaine on both days in the test chamber. The unpaired group received cocaine in regular room on day 1, and cocaine in the test chamber on day 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Cocaine-induced increases in EEG alpha and beta activity: evidence for reduced cortical processing.

To understand the effects of cocaine on the cerebral cortex, 14 male polydrug abusers were enrolled in a study on the effects of cocaine on the electroencephalogram (EEG). The experimental treatments were placebo, 20 mg cocaine or 40 mg cocaine i.v. administered in a double-blind, pseudorandom design. The EEG was recorded from 13 electrode positions over the left hemisphere during a 3-minute baseline recording and for 30 minutes after initiation of the i.v. injection. The spectral power for delta, theta, alpha and beta EEG bands was calculated from data collected in each 3-minute interval. Cocaine significantly increased beta in frontal and central areas and enhanced alpha in frontal and temporal regions. Cocaine-induced increases in EEG beta power had a cortical distribution similar to those produced by barbiturates and benzodiazepines. As all of these drugs reduce cortical glucose metabolism, the increases in beta power may reflect a reduction in cortical neural activity.

Adult

Effects of cocaine on P3B in cocaine abusers.

Little is known about the effects of cocaine on cognitive tasks. Event-related potentials (ERP) were recorded in 7 cocaine abusers during the performance of the auditory oddball task before and after the intravenous injections of saline and cocaine (60-80 mg). The P3B and slow wave components of the ERP were significantly larger 60-210 min after the cocaine than after the placebo injection. The results suggest that cocaine abusers have difficulty in maintaining optimal stimulus processing during extended testing. Cocaine blocks this decrement in stimulus processing.

Adult

Changes in mood, craving, and sleep during short-term abstinence reported by male cocaine addicts. A controlled, residential study.

We examined changes over 28 days in mood states, craving for cocaine, and sleep during short-term abstinence reported by 12 male, predominantly intravenous-using, cocaine-addicted subjects residing in a research facility. For comparison, we examined 10 nonaddicted control subjects. There were no significant differences between cocaine addicts and controls regarding demographics and selected DSM-III-R diagnoses other than psychoactive substance use disorder and antisocial personality disorder. There were significantly higher scores of psychiatric symptoms reported by cocaine addicts 1 week before admission. Mood-distress and depression scores recorded at admission and during short-term abstinence were significantly greater than those reported by controls. Addicts' mood-distress scores and craving for cocaine were greatest at admission and decreased gradually and steadily during the 28-day study. There were no significant differences between groups regarding reports of sleep other than difficulty falling asleep and clearheadedness on arising. Although there were significant differences in resting heart rate at admission and over time, there were no significant differences in weight gain or blood pressure. Given the absence of a classic "withdrawal" pattern, "short-term abstinence" may be a more appropriate classification of psychological and physical phenomena experienced by cocaine addicts who initiate abstinence in a controlled environment.

Adult

Dose-dependent atropine-induced changes in spontaneous electroencephalogram in human volunteers.

Atropine is an anticholinergic drug used in military medicine as an antidote following exposure to cholinesterase-inhibiting nerve agents. However, atropine causes neuropsychologic effects that impair performance. In the present study, we examined electrophysiologic indices that may accompany performance deficits. Quantitative electroencephalographic (EEG) analyses of changes induced by atropine (1.5, 3.0, and 6.0 mg/70 kg, intramuscularly) were assessed in seven male volunteers in a placebo-controlled, double-blind, cross-over experiment. Spontaneous EEG recordings were obtained from relaxed subjects before, 2 hours after, and 8 hours after atropine. Atropine significantly increased delta power, decreased alpha power, and tended to increase theta power and reduce beta and theta frequency. EEG indices of vigilance were reduced by the drug. Dose-related increases in sedation and dysphoria were obtained; some subjects liked these effects. Together, these findings confirmed that atropine causes dose- and time-related electrophysiologic and subjective effects that predict impaired performance.

Adult

Auditory event-related potentials in adolescents at risk for drug abuse.

We evaluated sensory and cognitive information processing in noninstitutionalized delinquent male adolescents and in age-matched low delinquency controls. Detailed psychometric testing documented the nature of the aggressive behavior of these young men. Deficits in information processing, as assessed by event-related potential (ERP) techniques, were observed at several levels of the auditory system in the delinquent group. The delinquent group showed delays in wave V of the brainstem auditory evoked potential, shorter N100 latency, and decreased slow wave amplitude of cognitive event-related potentials when subjects were asked to perform a mental task in a noisy environment. It remains to be determined whether or not such information-processing deficiencies are common among delinquent populations and how they might influence the development of delinquent behavior and drug abuse.

Adolescent

EEG and brainstem auditory evoked response potentials in adult male drug abusers with self-reported histories of aggressive behavior.

Auditory brainstem evoked response (BAER) and spontaneous electroencephalogram (EEG) were measured in 124 adult male drug abusers. We examined the relationships among psychiatric diagnoses, paper and pencil measures of aggression and hostility, and electrophysiological features. Subjects meeting criteria for antisocial personality disorder (ASP), as defined by DSM-III, were not significantly different from non-ASP subjects for either BAER or spontaneous EEG measures. The more overtly aggressive subjects had significant delays in BAER latency. Aggressive subjects also had more delta activity and less alpha activity in the spontaneous EEG, as have been observed in "psychopaths" and "criminals." Although ASP and aggression are related, these data indicate that aggressiveness may be a separate, albeit overlapping, trait. As both early aggression and a diagnosis of ASP are predictors of later drug use, the findings that only aggression was associated with EEG slowing and brainstem delays may indicate that ASP and aggression make independent contributions to vulnerability to the development of drug abuse.

Adult