Hilary Naylor

A low dose of subcutaneous nicotine improves information processing in non-smokers

Many studies have found that cigarette smoking or nicotine improves mental functioning in abstinent smokers. An unresolved issue is whether this improvement is due primarily to a direct facilitation of performance or to relief of the impairment caused by nicotine withdrawal. We evaluated the performance of 12 non-smokers before and twice (15 and 45 min) after a subcutaneous injection of 0.8 mg nicotine, 0.8 ml saline, and a control no treatment, on a choice reaction time (RT) task. Each treatment was given on a separate day; the control day was given on the first session. The order of nicotine and saline was balanced between subjects, and injections were given double-blind. The RT task manipulated stimulus and response processing. These manipulations consisted of two levels of stimulus complexity and two levels of response complexity, resulting in four task conditions. These manipulations along with latency measures of the event-related potential were used to identify the components of processing that mediated nicotines effects on performance. During each active drug session blood nicotine levels, cardiovascular, and subjective responses were measured before and after each of the three tests (pre-drug, 15 min and 45 min post-drug). For the information processing measures only the comparisons of the pre- and 15-min post-test showed significant drug effects. Nicotine compared to saline significantly increased the number of responses at the fast end of the RT distribution. However, there were no changes in accuracy. Nicotine also speeded mean RT compared with saline or the control day, but the effects were only significant for the control-nicotine comparison. There was an interaction between effects of nicotine and the task variables, such that nicotine speeded P3 latency in the hardest task condition, while slowing it in the other task conditions. Nicotine significantly increased heart rate, which lasted for the entire session. Blood nicotine levels were lower than expected from a preliminary study in smokers and may have been responsible for the smaller than expected mean RT effects. These findings suggest that even a low dose of nicotine directly affects attention or stimulus processing components of information processing. This study also illustrates the importance of assessing both multiple components of information processing and nicotine levels when examining the effects of nicotine on cognition.

Effects of oral scopolamine on human stimulus evaluation.

In a previous study of the effect of age on information processing, both age and stimulus complexity slowed reaction time (RT) and the latency of the P300 component of the brain event-related potential (ERP). The aim of the present study was to compare the effects of scopolamine (an anticholinergic) with the previously noted effects of age. The choice of scopolamine was prompted by current hypotheses concerning decline in cholinergic function with age.Twelve adult women were studied on a battery of tasks before and after scopolamine in oral doses of 0.0 (placebo), 0.6 and 1.2 mg. Reaction times (RT) and event-related potentials (ERP) were measured. The principal task was one that combined two levels of stimulus complexity and two levels of response difficulty to provide four subtasks. Scopolamine slowed RT and P300 as had age, but scopolamine slowed responses to simple stimuli more than responses to complex stimuli. Scopolamine effects on other tasks in the battery were small but consistent with an action of scopolamine on an early stimulus preprocessing stage that is independent of a stimulus evaluation stage that is also affected by age.

Cholinergic activity and constraints on information processing.

In humans, close relationships are found between cholinergic activity and constraints placed on information processing operations. This is true for all operations where the effects of cholinergic activity have been studied. Studies of vigilance, memory, problem solving, stimulus processing and response processing are cited as illustrations. These studies suggest the hypothesis that cholinergic activity controls constraints in all information processing operations. Alternative hypotheses are proposed and experimental tests are suggested.

A comparison of methods for quantitating fetal heart rate variability

Fetal heart rate (FHR) variability is thought to be an important index of fetal health. In the presence of normal variability, the fetus is vigorous, but lack of beat-to-beat variability may be associated with fetal compromise. A distinction between short-term variability (STV) (beat-to-beat changes between successive beats) and long-term variability (LTV) (rhythmic fluctuations in FHR) has not been made to date. We have utilized computer programs to compare three pairs of mathematical indices and one visual index of FHR variability. Among the three pairs of indices designed for detection of STV and LTV, de Haans short-term and long-term indices exhibited the least interdependence, and the long-term index was completely insensitive to artifically generated pure STV. Yehs short-term and long-term indices exhibited substantial positive interdependence. Hons visual index appears to detect LTV primarily rather than STV. When the effect of progression of labor on FHR variability was examined, no conclusions were possible because of inconsistencies between patients. Ultimately, the clinical value of any one of these indices awaits testing of their ability to define fetal well-being or fetal distress.

The effect of methylphenidate on information processing

Models of information processing currently popular in cognitive psychology divide the reaction process into a series of discrete separable stages. The distinction between one stage and another is verified by the additive factors method (AFM) as defined by Sternberg (1969). Task factors that do not interact with each other are inferred to affect different stages. The distinction between stimulus evaluation stages and response selection stages has been supported by brain event related potential (ERP) studies. The latency of the P300 component of the ERP is sensitive to changes in stimulus complexity but not to to changes in response complexity. The focus of this research is to determine the effects of stimulant drugs on stages of information processing using both reaction time (RT) and P300 latency within an AFM framework. four doses of methylphenidate (MP) were used in a within-subjects design to examine the effects of MP on stimulus and response processing. We found that MP speeds RT, and that this effect does not interact with the effect of stimulus complexity on RT. MP dose interacts with response complexity, the dose for optimal speeding varying with the level of complexity. The latency of P300 is increased by stimulus complexity, and not by response complexity, nor is it affected by MP. These results show that the stimulant drug acts on processes involved in response selection, rather than in stimulus evaluation. Individual differences in drug response are dose dependent, but also point to an effect on response processing.

Visual evoked potential changes induced by methylphenidate in hyperactive children: Dose/response effects

Visual event related potentials (ERP) were recorded from 21 hyperactive children aged 7-13 years under two attention conditions at 4 levels of methylphenidate dose (placebo, low, medium and high). ERP measures were very sensitive to age (under or over 10 years) and attention condition, but less sensitive to drug dose. There appeared to be two classes of drug dose effect on ERP amplitude, those that changed monotonically with dose and those from which dose interacted with attention non-monotonically. Drug effect on ERP amplitude may also depend on age so that opposite effects may occur in young and old children. No latency measures showed a dose effect. It appears that methylphenidate can speed reaction times without shortening ERP latency. This suggests the drug acts more on response-related processes than on stimulus evaluation.

Effects of cotinine on information processing in nonsmokers.

Abstract Cotinine, the major proximate metabolite of nicotine, is present in smokers in higher concentrations and for a longer time than nicotine, yet its effects on information processing have not previously been reported. We studied the cognitive effects of cotinine in non-smokers. Sixteen subjects were tested on three doses of cotinine (0.5, 1.0, and 1.5 mg cotinine base/kg), and placebo, on a choice reaction time (RT) task and on a verbal recall task with short and long lists. Cotinine significantly impaired recall on the long list and displayed non-significant but generally consistent dose-related slowing of RT and N100 latency. The acute effects of cotinine were small, and probably do not account for the cognitive deficits observed in tobacco withdrawal, although the cognitive effects of chronic cotinine administration need to be investigated.

Drugs and human information processing

Human performance on a choice–reaction time task (Eriksen task) has been simulated by a neural network. In simulations, the network captures many features of normal performance. In addition, changing gain in different layers produces changes that simulate different drug-induced changes. Data from a similar choice–reaction time task have been reanalyzed to test some of the predictions derived from changing gain in different layers. Clonidine antagonizes norepinephrine and acetylcholine activities and changes speed–accuracy tradeoff (i.e., increased frequency of errors at any specified reaction time). That is predicted when gain is reduced in lower layers (attention layer and input layer) of the network. By contrast, manipulating dopamine activity (with pimozide and amphetamine) changes reaction time without changing speed–accuracy tradeoff functions. That is predicted when gain is changed in the output layer of the network.

The effects of the human immunodeficiency virus on visual information processing

Only one study that we are aware of has examined subjects infected with human immunodeficiency virus (HIV) in the context of information processing, and that study was limited in that processing stages could only be inferred from reaction time (Perdices and Cooper 1989). By employing a visual reaction-time task while also measuring brain event-related potentials (ERPs), we obtained additional information that could be interpreted within the framework of an information processing model (Callaway 1984; Nayior et al 1987), and compared to non-information processing visual ERP studies of HIV-positive subjects. The purpose of our study was to determine whether we could identify information processing changes associated with HIVpositive status before onset of late-stage disease symptoms, i.e., before an acquired immune deficiency syndrome (AIDS) or AIDS dementia complex diagnosis. The ability to detect such changes could have important implications in the assessment of new drug therapies and the management of HIV-related cognitive dysfunction if such information reliably marks disease progression and/or predicts AIDS dementia complex development. Our secondary goal was to determine whether any information processing changes could be related to the known cognitive effects of a drug or class of drugs. If so, we might shed more light on the neurotransmitter system(s) most affected by the disease and possibly suggest a therapeutic substitution for its neurotransmitter deficiencies (Carlsson 1987).