Caffeine effects on resting-state arousal in children

From previous work in our laboratory, increases in skin conductance level (SCL), together with global (across-scalp) decreases in electroencephalogram (EEG) alpha power and increases in alpha frequency, are useful indices of arousal increase, and here we sought to identify changes in these indices with caffeine ingestion in children. We explored the effects of a single oral dose of caffeine (80 mg) in a randomised double-blind placebo-controlled repeated-measures cross-over study. Thirty healthy children aged between 8 and 13 years (mean age 10.5 years; 11 females) participated in two sessions, 1 week apart. EEG and SCL from a 3 min eyes-closed epoch, commencing approximately 30 min after ingestion of caffeine or placebo, were examined. Caffeine was associated with increased SCL, and a global reduction in EEG power in the theta and alpha bands, as well as topographically-focused reductions in delta and beta power, and a focal increase in alpha frequency. Only global alpha level demonstrated the expected inverse relationship with SCL in both placebo and caffeine conditions. These results are generally consistent with recent electrodermal and EEG studies of arousal. Together with our previous adult data, they indicate that caffeine can be used to increase arousal in both adults and children, without the potential confounds associated with varying task demands. Caffeine appears useful as a simple tool for manipulating arousal in studies exploring its role in physiological and behavioural functioning. This may be helpful in determining the role of hypothetical arousal anomalies in syndromes such as attention-deficit/hyperactivity disorder.     

Caffeine effects on resting-state electrodermal levels in AD/HD suggest an anomalous arousal mechanism

The effect of a single oral dose of caffeine was examined in a randomised double-blind placebo-controlled repeated-measures cross-over study. Eighteen children with AD/HD, aged between 8 and 13 years, were individually age- and gender-matched with a control group. All children participated in two sessions, one week apart. Skin conductance level (SCL) from a 3 min eyes-closed epoch, commencing 30 min after ingestion of caffeine or placebo, was examined. Across conditions, mean SCL was lower in the AD/HD group than controls, confirming hypoarousal in AD/HD. Caffeine produced an increase in SCL, and this increase did not differ between the groups. However, arousal increases were dose-dependent in controls, but not in AD/HD. Rather, caffeine-induced arousal increases in the AD/HD group were positively related to their hyperactivity/impulsivity levels. This suggests an anomalous arousal mechanism in AD/HD functionally related to impairment in one symptom dimension.     

Psychophysiological effects of habitual caffeine consumption

Caffeine is the most widely consumed pharmacologically active substance in the world, and a key issue concerning its possible implications for human health is whether it has persistent (i.e., chronic) physiological effects on habitual consumers. This study examined blood pressure, heart rate (HR), electromyogram (EMG), and skin conductance level (SCL) in 36 healthy men and women exposed to a pattern of moderate intake. A double-blind placebo-controlled crossover design with counterbalancing was used in which all subjects participated in four experimental conditions involving the ingestion of placebo or caffeine three times daily for 6 days followed by a seventh (“challenge”) day of placebo or caffeine ingestion. Results confirmed that caffeine has significant pressor effects, and these were found to be additive to the pressor action of a laboratory stressor. Following habitual consumption of the drug, pressor effects were diminished (indicative of tolerance) but not eliminated. Effects of caffeine on other parameters were either modest (HR and EMG) or negligible (SCL). Considering the near-universal use of caffeine, the persistent pressor effects observed in this study have important implications for clinical practice and public health. This article was supported in part by Australian Research Council Grant No. A79131683 and Australian National Health and Medical Research Council Grant No. 910794     

Extraversion and Multiple Levels of Caffeine-Induced Arousal: Effects on Overhabituation and Dishabituation

Psychophysiological tests of the Eysenck hypothesis that introverts are more arousal prone than extraverts have yielded somewhat mixed results. In an attempt to clarify and extend previous findings, the present study manipulated arousal level, using caffeine. Extreme groups of 48 extraverts and 48 introverts were used, and each subject was randomly assigned to a low, medium, or high dosage of caffeine or a placebo. Each subject heard a series of tones until criterion electrodermal habituation occurred. This was followed by dishabituation, overhabituation, and a further dishabituation procedure. Increasing caffeine dosages produced a linear increment in tonic levels in extraverts, but had little effect on SCL in introverts. Higher caffeine dosages also increased phasic response amplitudes in extraverts but decreased amplitudes in introverts. Although somewhat complex, results were partially supportive of the Eysenck hypothesis.     

Effects of habitual caffeine use and acute ingestion: testing a biobehavioral model.

A recently proposed model of the biobehavioral effects of caffeine suggests that acute ingestion impacts physiology and behavior differentially depending on the level of habitual usage of the drug. Acute ingestion and habitual usage are particularly expected to affect arousal and attentional processes. Subjects in the present study were preselected for high and low habitual caffeine use, given caffeine or a placebo, exposed to white noise or no white noise, and asked to perform on several tasks. Included were an arousal/habituation task (pure tones), reaction time, paired associates, anagrams, and vigilance. Electrodermal activity and performance were recorded. As predicted, virtually all effects were on the arousal/habituation and attentional (vigilance) tasks. Both acute ingestion and habitual use increased tonic EDA, and chronic use also reduced phasic responding, especially in the presence of a strong habituating stimulus. Both acute and habitual use also liberalized the vigilance response criterion, in that subjects risked more false alarms in order to attain more hits. In addition, habitual use increased sensitivity and reduced accuracy, and acute ingestion increased vigilance response time in the presence of white noise. Overall, the model was partially supported by these early results, though considerable further research is needed.     

Sex differences in adult ADHD: a double dissociation in brain activity and autonomic arousal

It is now estimated that up to one-half of attention deficit hyperactivity disorder (ADHD) children continue to manifest symptoms in adulthood. A striking discrepancy between juvenile and adult populations is the increasing proportion of females with an ADHD diagnosis. To shed light on the psychophysiological mechanisms underlying adult ADHD, electroencephalography (EEG) and electrodermal index of arousal (skin conductance level or SCL) measures were employed under conditions of eyes-closed resting activity. Quantitative EEG (QEEG) and SCL were measured simultaneously and continuously (2 min) in 35 ADHD adults (21 males, 14 females) and their age- and sex-matched controls. As a group ADHD adults were found to have EEG and SCL deviations consistent with previous adolescent and juvenile studies. However, adult males (but not females) with ADHD showed increased EEG theta activity. By contrast, adult females (but not males) with ADHD were autonomically hypo-aroused (decreased SCL). These results suggest that distinct mechanisms may underpin adult ADHD in males and females.     

Caffeine use as a model of acute and chronic insomnia.

It was hypothesized that the metabolic effects of caffeine, which can be objectively measured (i.e. physiological, "arousal"), could be used to develop a physiological arousal model of chronic insomnia in a group of normal young adults. Twelve normal young adult males participated for 11 nights after laboratory adaptation. Subjects received 400 mg of caffeine three times a day for 7 nights and days. As predicted, the use of caffeine resulted in increased metabolic rate. Sleep efficiency was significantly reduced by caffeine and multiple sleep latency tests (MSLTs) were significantly increased. Some adaptation to the metabolic, sleep efficiency, and MSLT effects of caffeine was seen over the week of administration. Withdrawal effects (i.e. rebound sleep or sleepiness) were not seen for metabolic, MSLT or sleep variables. The data indicated that caffeine was effective in producing significant metabolic and sleep effects and that those effects were related. The results were consistent with the interpretation that a chronic decrease in sleep efficiency associated with increased physiological arousal, although producing subjective dysphoria, does not produce a physiological sleep debt.     

Effects of caffeine on plasma renin activity, catecholamines and blood pressure.

Using a double-blind, randomized, cross-over protocol, we studied the effect of a single dose of oral caffeine on plasma renin activity, catecholamines and cardiovascular control in nine healthy, young, non-coffee drinkers maintained in sodium balance throughout the study period. Caffeine (250 mg) or placebo was administered in a methylxanthine-free beverage to overnight-fasted supine subjects who had had no coffee, tea or cola in the previous three weeks. Caffeine increased plasma renin activity by 57 per cent, plasma norepinephrine by 75 per cent and plasma epinephrine by 207 per cent. Urinary normetanephrine and metanephrine were increased 52 per cent and 100 per cent respectively. Mean blood pressure rose 14/10 mm Hg one hour after caffeine ingestion. There was a slight fall and then a rise in heart rate. Plasma caffeine levels were usually maximal one hour after ingestion but there was considerable individual variation. A 20 per cent increase in respiratory rate correlated well with plasma caffeine levels. Under the conditions of study caffeine was a potent stimulator of plasma renin activity and adrenomedullary secretion. Whether habitual ingestion has similar effects remains to be determined.     

The effect of caffeine ingestion on the perceived instability of visual patterns.

The unique cytoarchitecture of the visual cortex, with cells of particular orientation-specificity arranged in vertical columns adjacent to other columns with somewhat different orientation-specificity causes subjective visual instabilities when viewing some repetitive grid patterns for normal subjects. Since caffeine increases cortical arousal by serving as an antagonist to the inhibitory neurotransmitter adenosine, caffeine intake might be expected to increase these subjective disturbances. Twenty subjects were administered a placebo, 100 or 200 mg of caffeine orally. After 40 min subjects rated the level of visual instability on nine subjective dimensions, while viewing grating patterns. Each subject was tested on all levels of caffeine intake, with at least 48 h between tests. With increasing caffeine dosage the level of reported visual disturbances increased. These data suggest that the increased cortical arousal associated with caffeine intake may interact with the structural properties of the visual cortex to increase the perceptual instability associated with viewing grid patterns.     

Effect of caffeine on RPE and perceptions of pain, arousal, and pleasure/displeasure during a cycling time trial in endurance trained and active men

Caffeine has been reported to alter perceptions of exertion, muscle pain, and mood, yet the majority of existing data were obtained in resting volunteers or during steady-state exercise. The primary aim of this study was to examine the effects of caffeine on rating of perceived exertion (RPE) and perceptions of leg pain, arousal, and pleasure/displeasure during a simulated cycling time trial. Endurance-trained (n=8, VO(2)max=57.5±3.9 mL/kg/min) and active (n=8, VO(2)max=46.5±6.3 mL/kg/min) men initially completed two familiarization trials separated by at least 48 h. Over the next three trials, they completed a 10 km time trial preceded by ingestion of drinks containing caffeine (5 mg/kg ingested on 2 separate days) or placebo. Treatments were ingested using a single-blind, crossover design, and participants were deceived as to the content of all drinks. During exercise, RPE (6-20 scale), leg pain (0-10 scale), arousal (Felt Arousal Scale), and pleasure/displeasure (Feeling Scale) were recorded using various categorical scales. Repeated measures analysis of variance was used to assess differences in all variables across time and treatments, with fitness level used as a between-subjects variable. Pleasure/displeasure was altered (p<0.05, partial eta-squared (η(2))=0.23) with caffeine compared to placebo, although leg pain, RPE, and arousal were similar (p>0.05) across treatments. Caffeine increased (p<0.05, η(2)=0.27) cycling performance by 0.3-2.0% versus placebo, with no effect (p>0.05) of fitness level. Only in trained men; however, was there a significant caffeine-mediated improvement in cycling performance, which was consequent with diminished mood in trained and improved mood in active individuals.     

Psychophysiological investigations in depersonalization disorder and effects of electrodermal biofeedback

Previous studies investigating depersonalization disorder (DPD) report a lower baseline skin conductance level (SCL) and attenuated skin conductance response (SCR) to emotive stimuli. We hypothesized that increasing physiological arousal levels via electrodermal biofeedback may ameliorate disembodiment and emotional numbing symptomatology. Real-time versus sham biofeedback yielded a significant SCL increase after just 3 real-time biofeedback sessions in healthy volunteers. Subsequently, a randomized controlled biofeedback trial was administered with DPD patients. Findings were not replicated as SCL tended to fall, curiously more substantially in the real-time condition, concomitant with increased low- and high-frequency heart rate variability. To further investigate abnormal autonomic regulation in DPD, we compared basal autonomic activity between patients and healthy volunteers and found the former to be significantly more labile, indexed by greater nonspecific SCRs and higher resting SCLs. Rather than low sympathetic arousal, DPD might be better characterized by abnormal autonomic regulation affecting emotional and physiological responsivity.     

Caffeine and novelty: effects on electrodermal activity and performance

Caffeine has been shown to affect both physiological functioning and certain aspects of performance. These effects are typically attributed to a simple increase in general arousal. The present study was based on the theory that the effects of caffeine are actually multidimensional. Specifically, we hypothesized that the drug raises arousal, acts to maintain elevated arousal under conditions otherwise conductive to habituation, and enhances the impact of situational and psychological sources of arousal. Subjects were given caffeine (300 mg) or placebo and white noise or no noise and exposed to a series of pure tones and two Backwards Recall Tasks, one novel, the other repetitive. Electrodermal activity (EDA) and task performance were recorded. Caffeine increased arousal as measured by EDA. It also acted to slow habituation during repetitive stimulation, thus maintaining heightened arousal. Finally, it enhanced the effects of novel stimulation, which also independently raised arousal. These results support a multidimensional theory of caffeine effects and provide some understanding of the popularity of caffeine as a psychotropic agent.     

Effects of nicotine and caffeine, separately and in combination, on EEG topography, mood, heart rate, cortisol, and vigilance

Effects of nicotine and caffeine, separately and in combination, were assessed in 12 male habitual smokers in a repeated-measures design. Caffeine (0-mg vs. two 150-mg doses administered in a decaffeinated/sugar-free cola drink post-baseline and 90 min later) was crossed with nicotine (ad libitum own dosing vs. 1.0-mg machine-delivered dose vs. 0.05-mg machine-delivered dose). Participants smoked a total of five cigarettes at 30-min intervals over a 2-hr period. Caffeine and nicotine had large effect sizes on electroencephalogram (EEG) power; however, these effects were modulated by the eyes open versus closed condition, the other drug, and electrode site. EEG effects of open versus closed eyes tended to be of the same size and direction as those of nicotine and caffeine. However, whereas nicotine increased EEG power in some higher frequency bands in some conditions, caffeine decreased EEG power across almost all conditions. Serum cortisol concentration, vigor, and pleasantness were increased by nicotine, but not by caffeine. Level of depressive mood depended on an interaction of caffeine and nicotine. Vigilance performance was enhanced significantly by caffeine and was increased almost significantly by nicotine. The findings were interpreted in terms of common and differential mechanisms of the two drugs.     

Effect of acute administration of an herbal preparation on blood pressure and heart rate in humans

Confusion and controversy exist regarding the cardiovascular effects of dietary supplements containing caffeine and Citrus aurantium (bitter orange) extract. The primary protoalkaloidal ingredient in bitter orange extract is p-synephrine which has some structural similarities to ephedrine and nor-epinephrine, but exhibits markedly different pharmacokinetic and receptor binding properties. The goal of this study was to investigate the cardiovascular effects of a product containing caffeine, bitter orange extract (p-synephrine) and green tea extract in mildly overweight individuals. Fourteen female and nine male subjects (age 24.7 ±7.4 yrs, BMI: 26.6 ±3.8) volunteered in this randomized, placebo-controlled, crossover, double-blind designed study. On day one, subjects entered the laboratory following an overnight fast. Heart rate and blood pressure were recorded at 60 min. Expired air was analyzed for the next 10 min of the session. At each of three meals, subjects ingested one capsule that was either a non-caloric placebo or a dietary supplement that contained 13 mg p-synephrine and 176 mg caffeine. On the following day, the subjects returned and repeated the protocol for data collection beginning 60 min after consuming one capsule of the placebo or the dietary supplement. No effects of the dietary supplement on heart rate, systolic and diastolic blood pressure or mean arterial pressure were observed. No between or within group differences were observed when data were analyzed for gender and caffeine usage. A small but significant decrease in resting respiratory exchange ratio was observed for the low caffeine user group in response to the product containing caffeine and p-synephrine. The results of this study indicate that ingestion of a product containing bitter orange extract, caffeine and green tea extract does not lead to increased cardiovascular stress and that fat oxidation may increase in certain populations.     

Characterizing the psychophysiological signature of boredom

Research on the experience and expression of boredom is underdeveloped. The purpose of the present study was to explore the psychophysiological signature of the subjective experience of boredom. Healthy undergraduates (n = 72) viewed previously validated and standardized video clips to induce boredom, sadness, and a neutral affective state, while their heart rate (HR), skin conductance levels (SCL), and cortisol levels were measured. Boredom yielded dynamic psychophysiological responses that differed from the other emotional states. Of particular interest, the physiological signature of boredom relative to sadness was characterized by rising HR, decreased SCL, and increased cortisol levels. This pattern of results suggests that boredom may be associated with both increased arousal and difficulties with sustained attention. These findings may help to resolve divergent conceptualizations of boredom in the extant literature and, ultimately, to enhance our understanding and treatment of clinical syndromes in which self-reported boredom is a prominent symptom.     

EEG AND AUTONOMIC RESPONSE PATTERN DURING WAKING AND SLEEP STAGES

The response hierarchy of EEG and autonomic variables to tones of increasing intensity was studied during waking and sleep stages 2, REM, and SW (3 & 4 combined). Tones of 1000 Hz (5 sec duration, 55 sec ISI) were presented to 35 young adult male subjects. During waking, the tones began below awake auditory threshold and increased by 5 db until a motor response (button press) was made. During sleep, tones began at awake threshold and went to arousal threshold, i.e., motor response and/or an EEG change indicative of arousal. Changes in EEG, finger pulse amplitude, heart rate, skin potential, skin resistance, and respiration period were measured for each stimulus and were compared to a pseudostimulus response scored 25 sec prior to the actual stimulus. In the awake state, statistically significant responses (p < .05) were found for EEG, finger pulse, heart rate early deceleration, skin potential, and skin resistance to the tone at awake threshold, but not to tones at lesser db levels. During sleep, significant EEG responses were present to tones 30–25 db below arousal threshold, finger pulse 20–15 db below, and heart rate acceleration 20–5 db below. Significant skin potential, skin resistance, and motor responses were seen only at arousal threshold. Thus, in sleep, in contrast to waking, there were clear responses to stimuli below the arousal threshold, and there was definite ordering of the appearance of the various responses: EEG preceded the cardiovascular, with electrodermal and motor occurring only at arousal. This order was constant over sleep stages. Arousal thresholds were very similar across sleep stages in day sleepers (approximately 35 db above awake threshold). The threshold during stage 2 for night sleepers was about 15 db lower than that for day sleepers.     

Early morning driver sleepiness: effectiveness of 200 mg caffeine

Sleep-related vehicle accidents are prevalent early morning, especially in younger drivers. In two independent studies following a night of either restricted or nil sleep, young experienced drivers drove for 2 hr (0600-0800 h) continuously in an immobile car on an interactive, computer-generated, dull, and monotonous roadway. This exercise followed ingestion (at 0530 h) of 200 mg caffeine (= 2-3 cups coffee) versus placebo, counterbalanced, double blind. Driving incidents (lane drifting), subjective sleepiness, and 4-11 Hz electroencephalogram (EEG) activity were logged. In Study 1 (sleeping 0000-0500 h), caffeine significantly reduced incidents and subjective sleepiness throughout the 2-hr drive, and EEG power for the second 30-min period. In Study 2 (no sleep), sleepiness affected all measures profoundly, and driving was terminated after 1 hr. Nevertheless, caffeine reduced incidents significantly for the first 30 min and subjective sleepiness for the hour. This caffeine dose, feasibly taken via coffee, effectively reduces early morning driver sleepiness for about 30 min following nil sleep, and for around 2 hr after sleep restriction.     

Challenging sleep in aging: the effects of 200 mg of caffeine during the evening in young and middle-aged moderate caffeine consumers

The aim of this study was to evaluate the effects of a 200-mg administration of caffeine on polysomnographic sleep variables and quantitative sleep electroencephalography (EEG) in 12 young (20-30 years) and 12 middle-aged (40-60 years) moderate caffeine consumers (one to three cups of coffee per day). All subjects were submitted to both a caffeine (200 mg) and placebo (lactose) condition in a double-blind cross-over design. The conditions were separated by 1 week. Compared with the placebo condition, the evening ingestion of caffeine lengthened sleep latency, reduced sleep efficiency, and decreased sleep duration and amount of stage 2 sleep in both age groups. Caffeine also reduced spectral power in delta frequencies in frontal, central and parietal brain areas, but not in prefrontal (PF) and occipital regions. Moreover, caffeine increased spectral power in beta frequencies in frontal and central brain areas in both age groups. A suppression of spectral power in the PF area in low delta frequencies (0.5-1.00 Hz) and a rise in spectral power in the parietal region in high alpha (10.00-12.00 Hz) and beta frequencies (17.00-21.00, 23.00-25.00, 27.00-29.00 Hz) occurred solely in middle-aged subjects. No such changes were noticeable in young subjects. Generally, caffeine produced similar effects in young and middle-aged subjects. Only a few frequency bins showed more effects of caffeine in middle-aged subjects compared with young subjects. Furthermore, sleep EEG results do not entirely support the hypothesis that caffeine fully mimics the effects of a reduction of homeostatic sleep propensity when following a normal sleep-wake cycle.     

The effects of substrate utilization,manipulated by caffeine,on post-exercise oxygen consumption in untrained female subjects

Summary The effect of substrate utilization manipulated by caffeine on post-exercise oxygen consumption was investigated in five untrained females (age=21±1.5 years), following 90 min of treadmill walking at 55% maximal oxygen consumption. Each subject participated in the two trials (control and experimental) within 2 weeks of each other. Immediately following the measurement of resting oxygen consumption, subjects consumed one of the two test beverages 60 min prior to exercise: 5 mg of caffeine per kg of bodyweight in 200 ml of orange juice (CA) or 200 ml of orange juice (C). Assignment of CA and C was made in a random, double blind fashion. Immediately prior to the exercise phase (0 min) resting oxygen consumption was again measured. Following exercise, subjects returned to the same pre-exercise sitting position where respiratory data was collected over 1 h. No significant differences were found in resting oxygen consumption and respiratory exchange ratio (R) prior to caffeine ingestion (−60 min). One hour after caffeine ingestion (0 min) oxygen consumption and free fatty acid (FFA) levels increased significantly compared to C. During and 1 h following exercise, oxygen consumption and FFA levels were significantly greater, with R values being significantly lower in CA compared to C. These findings provide further evidence that metabolic substrate is somehow implicated in elevating oxygen consumption following exercise cessation.     

Excess beta activity in the EEG of children with attention-deficit/hyperactivity disorder: A disorder of arousal?

Past research has reported that a small proportion of children with attention-deficit/hyperactivity disorder (AD/HD) have excess beta activity in their EEG, rather than the excess theta typical of the syndrome. This atypical group has been tentatively labeled as hyperaroused. The aim of this study was to determine whether these children have a hyperaroused central nervous system. Participants included 104 boys aged 8 to 13 years old, with a diagnosis of either the Combined or Inattentive type of AD/HD (67 combined type), and 67 age-matched male controls. Ten and a half minutes of EEG and skin conductance (SCL) were simultaneously recorded during an eyes-closed resting condition. The EEG was Fourier transformed and estimates of total power, and relative power in the delta, theta, alpha, and beta bands, and the theta/beta ratio, were calculated. AD/HD patients were divided into an excess beta group and a typical excess theta group. Relative to controls, the typical excess theta group had significantly increased frontal total power, theta and theta/beta ratio, with reduced alpha and beta across the scalp. The excess beta group had significantly reduced posterior total power, increased centro-posterior delta, globally reduced alpha, globally increased beta activity, and globally reduced theta/beta ratio. Both AD/HD groups had significantly reduced SCL compared to the control group, but the two groups did not differ from each other on SCL. These results indicate that AD/HD children with excess beta activity are not hyperaroused, and confirm that the theta/beta ratio is not associated with arousal. This is the first study of arousal measures in AD/HD children with excess beta activity, and has implications for existing models of AD/HD.