Developmental changes in the human sleep EEG during early adolescence.

STUDY OBJECTIVES: To use time-frequency analysis to characterize developmental changes in the human sleep electroencephalogram (EEG) across early adolescence. DESIGN: Sleep EEG was recorded when children were 9/10 years old and 1 to 3 years later after sleeping at home on a fixed schedule for at least one week. SETTING: A 4-bed sleep laboratory. PARTICIPANTS: Fourteen (5 girls) healthy children ages 9/10 (mean = 10.13, SD = +/- 0.51) years at initial and 11 to 13 (mean = 12.28, SD = +/- 0.62) years at follow-up. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: All-night polysomnography was performed at each assessment and sleep stages were scored with Rechtschaffen and Kales criteria. Slow wave sleep minutes decreased from the initial to the follow-up session by 29%, while minutes of stage 2 increased by 17%. NREM and REM sleep EEG spectra from two central and two occipital leads were examined for developmental changes. All-night analyses showed a significant decrease of EEG power from the initial to follow-up session across a range of frequencies during NREM and REM sleep. This decline occurred across leads and states in the delta/theta bands (3.8 - 7 Hz). Time-frequency analyses indicated that this effect was consistent across the night. The decline in power with age was most pronounced in the left central and right occipital leads. The frequency of greatest power in the sigma band (11 - 16 Hz) was significantly higher at follow-up. CONCLUSIONS: This longitudinal analysis highlights asymmetrical frequency-specific declines in sleep EEG spectral power with early adolescent maturation, which may reflect early signs of the cortical synaptic pruning in the healthy adolescent.

Intracortical electroencephalography in acute brain injury.

OBJECTIVE: Continuous electroencephalography (EEG) is used in patients with neurological injury to detect electrographic seizures and clinically important changes in brain function. Scalp EEG has poor spatial resolution, is often contaminated by artifact, and frequently demonstrates activity that is suspicious for but not diagnostic of ictal activity. We hypothesized that bedside placement of an intracortical multicontact electrode would allow for improved monitoring of cortical potentials in critically ill neurological patients. METHODS: Sixteen individuals with brain injury, requiring invasive neuromonitoring, underwent implantation of an eight-contact minidepth electrode. RESULTS: Intracortical EEG (ICE) was successfully performed and compared with scalp EEG in 14 of these 16 individuals. ICE provided considerable improvement in signal-to-noise ratio compared with surface EEG, demonstrating clinically important findings in 12 of 14 patients (86%) including electrographic seizures (n = 10) and acute changes related to secondary neurological injury (n = 2, 1 ischemia, 1 hemorrhage). In patients with electrographic seizures detected by ICE, scalp EEG demonstrated no concurrent ictal activity in six, nonictal-appearing rhythmic delta in two, and intermittently correlated ictal activity in two. In two patients with secondary neurological complications, ICE demonstrated prominent attenuation 2 to 6 hours before changes in other neuromonitoring modalities and more than 8 hours before the onset of clinical deterioration. INTERPRETATION: ICE can provide high-fidelity intracranial EEG in an intensive care unit setting, can detect ictal discharges not readily apparent on scalp EEG, and can identify early changes in brain activity caused by secondary neurological complications. We predict that ICE will facilitate the development of EEG-based alarm systems and lead to prevention of secondary neuronal injury.

Brain electrical source differences between depressed subjects and healthy controls.

Many brain regions show metabolic and perfusion abnormalities in major depressive disorder (MDD), including anterior cingulate and prefrontal cortices. Some of these same areas also show abnormal function with low resolution electromagnetic tomography (LORETA). However, LORETA results are not always consistent across studies, nor with findings from other imaging modalities. These discrepancies may be due, among other factors, to the sensitivity of EEG source localization to different electrode montages. Thirty-six channel EEG was collected from healthy controls and age- and gender-matched unmedicated subjects with MDD (n = 74). EEGs were analyzed with LORETA to assess resting state current density at each of 2,394 cortical voxels. For comparison to previous studies, LORETA was performed using all electrodes or with specific prefrontal electrodes removed. Voxel-by-voxel differences between the depressed and healthy groups were calculated using non-parametric statistics. MDD subjects showed significantly elevated current density in delta, theta, alpha, beta1, and beta2 frequency bands relative to controls in anterior cingulate and prefrontal cortices. Removal of certain prefrontal electrodes from input to LORETA decreased or eliminated significant differences between groups. LORETA detects differences in brain activity between MDD subjects and healthy controls that are consistent with previous findings using other imaging modalities. Inconsistent findings among LORETA studies, and between LORETA studies and those using other functional imaging techniques, may result from differences in electrode montages.

Sleep in conduct-disordered adolescents--a polysomnographic and spectral power analysis study.

The aim of the present study was to characterize sleep in conduct-disordered adolescents using polysomnography and spectral power analysis. The two hypotheses were that conduct disorder would be associated with objective sleep problems, and that conduct disorder--as a precursor of adult antisocial personality disorder--would be associated with the same kind of abnormal sleep architecture, with both increased deep sleep and delta power, as previously reported in antisocial personality disorder. The patients consisted of 15 adolescents (age range 13-17 years, mean age 14.7 years) with histories of antisocial behavior so functionally impairing that they were ordered by child welfare to undergo a psychosocial evaluation in a closed social services ward. The healthy age-matched controls comprised 20 volunteers recruited with a newspaper advertisement. Opposite to earlier subjective sleep studies among conduct-disordered children, no significant differences in sleep parameters were observed between the two groups. The adolescents with conduct disorder slept a little bit longer, but the percentage amount of different sleep stages did not differ significantly between the two groups. Relative spectral power of sleep, delta power in particular, was similar in both groups, assessed in total sleep time as well as in first half of it. Different alternative explanations for these findings are discussed.

Acute cortisol administration increases sleep depth and growth hormone release in patients with major depression.

Acute administration of cortisol increases non-rapid-eye movement (non-REM) sleep, suppresses rapid-eye movement (REM) sleep and stimulates growth hormone (GH) release in healthy subjects. This study investigates whether cortisol has similar endocrine and electrophysiological effects in patients with depression who typically show a pathological overactivity of the hypothalamus-pituitary-adrenal (HPA) system. Fifteen depressed inpatients underwent the combined dexamethasone/corticotropin-releasing hormone test followed by three consecutive sleep EEG recordings in which the patients received placebo (saline) and hourly injections of cortisol (1mg/KG BW). Cortisol increased duration and intensity of non-REM sleep in particular in male patients and stimulated GH release. The activity of the HPA axis appeared to influence the cortisol-induced effects on non-REM sleep and GH levels. Stimulation of delta sleep was less pronounced in patients with dexamethasone nonsuppression. In contrast, REM sleep parameters were not affected by the treatment. These data demonstrate that the non-REM sleep-promoting effects of acute cortisol injections observed in healthy controls could be replicated in patients with depression. Our results suggest that non-REM and REM sleep abnormalities during the acute state of the disease are differentially linked to the activity of the HPA axis.

Different neuronal networks are associated with spikes and slow activity in hypsarrhythmia.

PURPOSE: West syndrome is a severe epileptic encephalopathy of infancy characterized by a poor developmental outcome and hypsarrhythmia. The pathogenesis of hypsarrhythmia is insufficiently understood. METHODS: We investigated eight patients with infantile spasms and hypsarrhythmia (group I) and 8 children with complex partial seizures (group II) using simultaneous recordings of electroencephalogram (EEG) and functional MRI. Hemodynamic responses to epileptiform discharges and slow wave activity (EEG delta power) were analyzed separately. RESULTS: In group I (mean age, 7.82 +/- 2.87 months), interictal spikes within the hypsarrhythmia were associated with positive blood oxygenation level-dependent (BOLD) changes in the cerebral cortex (especially occipital areas). This was comparable with cortical positive BOLD responses in group II (mean age, 20.75 +/- 12.52 months). Slow wave activity in group I correlated significantly with BOLD signal in voxels, which were localized in brainstem, thalamus, as well as different cortical areas. There was no association between BOLD effect and EEG delta power in group II. Moreover, as revealed by group analysis, group I differed from group II according to correlations between BOLD signal and slow wave activity in putamen and brainstem. CONCLUSIONS: This study demonstrates that multifocal interictal spikes and high-amplitude slow wave activity within the hypsarrhythmia are associated with the activation of different neuronal networks. Although spikes caused a cortical activation pattern similar to that in focal epilepsies, slow wave activity produced a hypsarrhythmia-specific activation in cortex and subcortical structures such as brainstem, thalamus, and putamen.

Cognitive deficits during status epilepticus and time course of recovery: a case report.

We describe a young woman with progressive cognitive and neurological deficits during a parietal lobe status epilepticus (SE). Ictal FDG-PET showed left parietal lobe hypermetabolism and frontal lobe hypometabolism with concomitant EEG slowing. Cognitive and neurological deficits fully reversed more than 1 year after seizure remission, and were associated with normalization of FDG-PET and EEG. Our findings suggest that ictal hypometabolism and EEG delta activity at a distance from the epileptic focus were seizure-related phenomena, possibly representing inhibition in seizure propagation pathways, which could be responsible for the epileptic encephalopathy.

Characteristic distribution of interictal brain electrical activity in idiopathic generalized epilepsy.

PURPOSE: To demonstrate the anatomic localization of the cortical sources of the interictal EEG activity in human idiopathic generalized epilepsy (IGE). METHODS: Multiple cortical and hippocampal sources of the interictal spontaneous EEG activity were investigated by low-resolution electromagnetic tomography in 15 untreated IGE patients and in 15 healthy controls. EEG activity (current density) in four frequency bands (delta: 1.5-3.5 Hz, theta: 3.5-7.5 Hz, alpha: 7.5-12.5 Hz, beta: 12.5-25.0 Hz) was computed for 2,397 voxels. Voxel-by-voxel group comparison was done between the patient and the control group. Voxels with p < 0.01 differences (between the two groups) were correlated with cortical anatomy. RESULTS: Areas of significantly increased or decreased activity were characterized by their anatomical extension and the frequency bands involved. Five areas of bilaterally increased activity were found: rostral part of the prefrontal cortex (delta, theta); posterior part of the insula (delta); hippocampus and mediobasal temporal cortex (all frequency bands); medial parietooccipital cortex (theta, alpha, beta); dorsal and polar parts of the occipital cortex (alpha). Bilaterally decreased delta, theta, alpha activity was found in the majority of the frontal and anterior parietal cortex on the lateral surface, and in parts of the medial surface of the hemispheres. The area of decreased beta activity was less extensive. The right lateral and laterobasal temporal cortex showed decreased delta, theta, alpha, and beta activity, while its left counterpart only showed decreased delta and alpha activity in a limited part of this area. CONCLUSIONS: (1) Pathological interictal EEG activity is not evenly distributed across the cortex in IGE. The prefrontal area of increased activity corresponds to the area that is essential in the buildup of the ictal spike-wave paroxysms (absence seizures). The existence of the posterior "center of gravity" of increased EEG activity in IGE was confirmed. The frontal area of decreased activity might be related to the cognitive deficit described in IGE patients. (2) Increased activity in a lot of ontogenetically older areas (including the hippocampi) and decreased activity in the majority of the isocortex is a peculiar pattern that argues for a developmental hypothesis for IGE.

Clinical correlates of occipital intermittent rhythmic delta activity (OIRDA) in children.

PURPOSE: The clinical significance of occipital intermittent rhythmic delta activity (OIRDA) on the electroencephalogram has not been fully established. Recent studies suggest that this pattern occurs almost exclusively in children and is probably of epileptic origin in most cases. We sought to characterize the electrographic features and clinical correlates of occipital intermittent rhythmic delta activity. METHODS: A review of 697 consecutive pediatric electroencephalograms detected occipital intermittent rhythmic delta activity in 24 studies. Mean patient age was 7.96 years. RESULTS: Recent convulsions and absence seizures constituted the main indications for the study. Concomitant, independent epileptiform activity was noted in half of the cases. This activity was focal in all but one case. Conversely, in most cases of absence seizures, epileptiform activity intermixed with occipital intermittent rhythmic delta activity. Furthermore, the frequency of the occipital rhythmic discharges in studies of children with absences was generally faster (3-4 Hz) than in localization-related epilepsy (2-3 Hz). Most patients were awake when occipital intermittent rhythmic delta activity occurred. Chronic encephalopathy was seen in one child only. Analysis of neuroimaging studies in eight cases revealed no structural pathology associated with occipital intermittent rhythmic delta activity. CONCLUSIONS: Occipital intermittent rhythmic delta activity is probably an epileptiform pattern, although it is noted occasionally in encephalopathic children. Its electrographic characteristics appear to differ between localization-related epilepsy and primary generalized epilepsy, particularly absence seizures.

Occurrence of a prolonged nonepileptic motor status after a febrile seizure.

PURPOSE: Febrile seizures are very common events in the pediatric population, and this disorder could be inherited. A previous article on nonepileptic status after a febrile seizure was published by Japanese authors. They described convulsive manifestations after a febrile seizure with an EEG counterpart characterized by delta activity and rhythmic theta discharges. We report two cases of nonepileptic prolonged motor status occurring after a simple febrile seizure, erroneously diagnosed as an epileptic status. METHODS: An EEG was obtained during the episode in both of the children; for one of them, we performed a video-EEG recording. RESULTS: In both children, this state was characterized by tonic, vibratory posture, and fluctuation of consciousness. The face was not involved, eyes were closed, and the children were not cyanotic. Ictal EEG showed alternating and mixed theta-delta activity. This activity appeared to be rhythmic in some periods. Clinical and EEG features did not change after administration of benzodiazepine. CONCLUSIONS: We believe this uncommon condition to be a nonepileptic phenomenon, occurring after a simple febrile seizure, with favorable prognosis.

Beta and gamma range EEG power-spectrum correlation with spiking discharges in DBA/2J mice absence model: role of GABA receptors.

PURPOSE: To describe the correlations between spiking pattern and EEG power spectrum frequency in DBA/2J mice, a model for murine absence seizures, after gamma-aminobutyric acid (GABA)(B) modulation. METHODS: The animals were first tested with the GABA(B) agonist l-baclofen followed by the GABA(B) antagonist SCH 50911. Moreover, digital EEGs recorded under experimental conditions were processed at baseline and 10 and 20 min after l-baclofen injection. This procedure was followed by injection of the GABA(B) antagonist SCH50911 and by an additional EEG evaluation at 10 and 20 min from drug administration. The power spectra analysis of signals was obtained for delta (0.5-3 Hz), theta (3.5-7.5 Hz), alpha (8-12 Hz), beta (13-20 Hz), and gamma (21-50 Hz) frequencies. RESULTS: The spiking pattern and power spectrum of beta activity was increased by 80%), whereas gamma power increased (correlation, 0.92; p < 0.001). The remaining frequency bands were unaffected. CONCLUSIONS: This study confirms the potential of GABA(B) antagonists in contrasting seizure absence in rodent models and suggests the application of drugs with a similar mechanism in humans. In addition, because GABA(B) antagonists not only contrast seizure in rodent models of absence but also improve "cognitive" performance, it could be hypothesized that gamma increase, correlated with optimized cortical binding during coherent percepts, may produce potential cognition-enhancing effects.

Lithium-induced confusional states: nonconvulsive status epilepticus or triphasic encephalopathy?

Lithium therapy can cause a confusional state by direct toxicity, precipitation of nonconvulsive status epilepticus, or by interplay with other neuroleptic medications to produce neuroleptic malignant syndrome or serotonin syndrome. These conditions resemble each other clinically, but EEG may help differentiate among them. We reviewed the EEG patterns with triphasic waves or rhythmic delta activity in lithium toxic patients and discuss clinical and EEG differentiation among syndromes. Lithium toxicity poses significant diagnostic challenges from EEG and clinical perspectives.

Correlation of severity of FDG-PET hypometabolism and interictal regional delta slowing in temporal lobe epilepsy.

PURPOSE: We investigated the association of severity of hypometabolism detected by positron emission tomography (PET) with [(18)F]fluorodeoxyglucose (FDG) and persistence of interictal EEG focal slowing in patients with refractory temporal lobe epilepsy. METHODS: Eighty temporal lobes of 40 consecutive patients with intractable temporal lobe epilepsy (mean age, 43.5 years) were studied. All patients underwent video-EEG monitoring, magnetic resonance imaging (MRI), and FDG-PET. Patients with either normal MRI or with unilateral mesial temporal sclerosis, but no other structural abnormality, were included. Interictal EEG delta slowing was graded as none, infrequent (one episode or less/hour), intermediate (more than one episode/hour), or continuous. PET hypometabolism was graded as none, mild, moderate, or severe. RESULTS: The severity of temporal lobe hypometabolism with PET was significantly correlated with the amount of delta activity in the interictal EEG, independent of MRI findings (Spearman r = 0.46; p < 0.0005). CONCLUSIONS: This observation suggests related underlying pathophysiologic mechanisms for metabolic and electrical dysfunction in temporal lobe epilepsy.

Homeostatic sleep response to naps is similar in normal elderly and young adults.

Delta homeostatic regulation can be challenged by reducing delta need with daytime naps and measuring delta in post-nap sleep. We previously demonstrated that, after a late afternoon nap, young adults reduce the amount of delta in post-nap sleep by the amount in the nap. We compared homeostatic responses of 19 young adults (mean age 22.4 years) and 19 normal elderly subjects (mean age 71.4 years). Each participated in four separate 2-day sessions that consisted of a baseline night, a nap, and post-nap sleep. Nap times were 0900, 1200, 1500 and 1800 h. The 1800 h nap contained the largest amount of delta and produced the largest reduction in post-nap delta. The young and elderly groups respectively produced 28 and 24% of baseline delta in the 1800 h nap. Both groups showed equivalent delta regulation, reducing post-nap delta by 28 and 25%, respectively. In both age groups, the decrease in post-nap delta resulted from a reduced rate of delta production (power/min) and reduced non-rapid eye movement (NREM) sleep duration. Period-amplitude analysis showed that the reduction in power/min resulted from decreases in delta wave amplitude and incidence. None of the responses to nap challenges differed significantly across age groups nor were there gender differences or age by gender interactions. These results show that delta homeostatic responses to naps in the elderly parallel those of young subjects. REM sleep showed no homeostatic reductions following naps in either group. We believe that the striking differences in the delta and REM responses point to different biological roles of the two kinds of sleep.

Interictal temporal delta activity in temporal lobe epilepsy: correlations with pathology and outcome.

PURPOSE: To determine the characteristics and the clinical significance of focal slow activity and its association with focal epileptogenesis in patients with temporal lobe epilepsy (TLE). METHODS: We analyzed the interictal EEGs of 141 patients who had temporal lobe resections for intractable focal seizures and correlated the findings with pathologic changes and outcome. The pathologic changes were categorized into medial temporal sclerosis, tumors, and nonspecific changes. RESULTS: Lateralized slow activity was found in 66% of the patients, and it was mainly temporal, of delta frequency and irregular morphology. None of its characteristics, including quantity and reactivity to eye opening, was substrate specific. It was highly concordant with temporal spiking (60%), without any difference across the three groups, but provided additional information in 19 (15%) patients who had no lateralizing spikes. The effect of sleep also was similar in all three groups and included transition of slow waves into spikes. Lateralized slow activity to the side of the operation was significantly associated with favorable outcome only in the group with nonspecific pathology (p = 0.008), regardless of the presence, laterality, or topography of spikes. CONCLUSIONS: Our findings suggest that in patients with TLE whose brain magnetic resonance imaging (MRI) is either normal or suggestive of medial temporal sclerosis, interictal temporal slow activity has a lateralizing value similar to that of temporal spiking. Its association with a favorable outcome in patients with nonspecific pathology also suggests that candidates with lateralizing temporal delta and normal MRI should not be barred from further preoperative assessment.

Rapid eye movement density shows trends across REM periods but is uncorrelated with NREM delta in young and elderly human subjects.

Saccade-like eye movements are the most prominent phasic component of rapid eye movement (REM) sleep. Eye movement density (EMD) appears to be negatively related to sleep depth. Thus, EMD is depressed by sleep deprivation. We sought to determine in 19 young normal (YN) and 19 elderly normal (EN) subjects: (a) whether EMD is correlated with delta EEG in baseline sleep; (b) whether EMD is increased by daytime naps; and (c) whether EMD patterns across sleep cycles differ in the two age groups. Subjects participated in four separate 2-day recording sessions, each consisting of a baseline night, a daytime nap, and post nap night. EMD was measured as 0.3-2 Hz integrated amplitude (IA)/20 s stage REM. EMD was not correlated with rate of non rapid eye movement (NREM) delta production (power/min) in the baseline sleep of either group. Changes in EMD and delta power/min on post nap nights also were uncorrelated. These data indicate that very strong changes in sleep depth (state) are required to overcome the individual stability (traits) of NREM delta and eye movement density. ANOVA for EMD across REM periods 1-4 showed a significant cycle effect and a significant age x cycle interaction. These effects were mainly due to YNs having depressed EMD in the first REM period, likely due to the low arousal level early in sleep in these subjects. Compared with waking saccades the saccade eye movements of REM sleep have received little investigation. Further study of these movements could shed new light on neurophysiology of REM sleep. Such studies might also be clinically useful because the density of these movements appears to be related to depression and (independently) to cognitive function in individuals with brain impairment.

Clinical correlation of occipital intermittent rhythmic delta activity.

Frontal intermittent rhythmic delta activity is associated with encephalopathy, and temporal intermittent delta activity is associated with epilepsy, but the importance of OIRDA (OIRDA) is less well defined. The authors reviewed retrospectively EEGs and medical records of 77 patients with OIRDA to determine whether they had epilepsy, acute encephalopathy, or another diagnosis. They compared the incidence of epilepsy in this population with a control group of 77 patients referred for EEG, matched for age, gender, and year of EEG. OIRDA was most commonly generalized, high amplitude, saw toothed, and reactive to eye opening, and with mean frequency of 2.89 +/- 0.50 Hz. Mean age was 8.1 +/- 4.5 years. Seventy-six of 77 patients were

Clinical and radiologic correlates of frontal intermittent rhythmic delta activity.

To assess the clinical and radiologic correlates of frontal intermittent rhythmic delta activity (FIRDA), the authors reviewed the hospital charts of patients whose EEGs depicted this EEG finding, and recorded their past medical and neurologic history, the reason for hospital admission, and their neurologic status both on admission and during EEG recordings. Laboratory results on admission and concomitant to the EEG recording, computed tomography, or MRI findings during hospital admission were also reviewed. Sixty-eight patients were assessed. The gender ratio was 1:1; mean age was 56 years. Chronic disease occurred in 78% of patients, including hypertension (34%), diabetes (32%), and renal failure (18%). On admission, renal failure (n = 34) and hyperglycemia (n = 22) were most prominent. The majority of patients had at least one abnormal laboratory result. Thirty-eight of 51 patients in whom the level of consciousness was stated during EEG were described as awake. More than half of 58 patients whose EEG background activity was stipulated demonstrated diffuse slowing, mostly in the theta range. MRI was abnormal in 15 of 17 patients. Intrahemispheric lesions, particularly ischemic and hemorrhagic, were most common (n = 10), followed by basal ganglia lacunae (n = 4). Computed tomography was abnormal in 29 of 44 patients. Hemispheric pathology, diffuse or localized, occurred in 22 patients. Frontal intermittent rhythmic delta activity is associated with mild to moderate encephalopathy and is detected principally in awake patients. Most patients in this series had chronic systemic illness. Old ischemic structural brain lesions may predispose some patients to develop FIRDA during acute metabolic derangement, such as uremia and hyperglycemia. Frontal intermittent rhythmic delta activity was not associated with EEG epileptiform activity. Deep midline lesions, posterior fossa tumors, and hydrocephalus were not detected in this series of patients with FIRDA.

Topographic quantitative EEG response to acute caffeine withdrawal: a comprehensive analysis of multiple quantitative variables.

Most previous studies of the neurophysiological effects of caffeine have focused on the effects of caffeine ingestion, and few studies have examined the effects of caffeine withdrawal. This open study evaluated the quantitative EEG (QEEG) changes occurring during a 4-day period of abstinence in subjects who habitually consume 300 mg or more of caffeine daily. Thirteen subjects underwent QEEG studies during their usual caffeine consumption (baseline) and on days 1, 2, and 4 of a 4-day period of caffeine abstinence. Ten of the subjects underwent a second QEEG on day 4 that consisted of a period of recording after reinstitution of caffeine. A comprehensive analysis of multiple quantitative variables was performed for each study during the abstinence period and compared to the variables obtained at baseline for each subject. Changes occurring during caffeine abstinence included: 1) increases in theta absolute power over all cortical areas, 2) increases in delta absolute power over the frontal cortex, 3) decreases in the mean frequency of both the alpha and beta rhythm, 4) increase in theta relative power and decrease in beta relative power, and 5) significant changes in interhemispheric coherence. Most of these changes tended to return to pre-abstinence baseline levels rapidly after resumption of caffeine consumption. The caffeine withdrawal state affects a number of neurophysiological variables. Further investigation of the neurophysiological aspects of caffeine withdrawal using placebo controlled double blind assessment methods is warranted.

Relationship between electroencephalogram slow-wave magnitude and heart rate variability during sleep in humans.

To explore whether depth of sleep is related to changes in autonomic control, continuous power-spectral analysis of the electroencephalogram (EEG) and heart rate variability (HRV) was performed in ten normal subjects during nocturnal sleep. Quiet sleep (QS) was associated with an increase in high-frequency power (HF) of HRV (0.15-0.4 Hz) but a decrease in low-frequency power (LF) (0.04-0.15 Hz) to HF ratio (LF/HF) compared with awakening. During QS, LF/HF was significantly and negatively correlated with delta power of EEG (0.5-4.0 Hz), whereas mean R-R interval and HF were not. We conclude that during QS, cardiac sympathetic regulation is negatively related to the depth of sleep, although vagal regulation is not. Our methodology offers a quantitative analysis to study the interaction between cerebral cortical and autonomic functions.