Brain wave components of the contingent negative variation in humans.

In a contingent negative variation paradigm with two stimuli paired at an interstimulus interval of 4 seconds, two distinct waveforms having functional and topographic differences are observed. An early wave is maximal over the frontal cortex and is elicited by the warning stimulus. A later wave, maximal over the motor cortex, precedes the imperative stimulus and is identified with preparation for motor response.

Synthesis of the contingent negative variation brain potential from noncontingent stimulus and motor elements.

Slow shifts in brain potential (commonly called the contingent negative variation), obtained during a warned reaction-time task with a foreperiod of 1 second, were compared with waveforms synthesized by the addition of separately obtained potentials associated with individual (nonpaired) sensory stimuli and self-initiated motor movements. The synthesized waveforms match closely the actual contingent negative variation, suggesting that it is constituted largely of separate, noncontingent elements related to sensory and motor processes.

Endogenous potentials generated in the human hippocampal formation and amygdala by infrequent events.

Infrequent, attended, auditory and visual stimuli evoke large potentials in the human limbic system in tasks that usually evoke endogenous potentials at the scalp. The limbic potentials reverse polarity over small distances and correlate with unit discharges recorded by the same electrodes, indicating that they are locally generated.

Features of the non-contact carotid pressure waveform: Cardiac and vascular dynamics during rebreathing.

This report amplifies and extends prior descriptions of the use of laser Doppler vibrometry (LDV) as a method for assessing cardiovascular activity, on a non-contact basis. A rebreathing task (n = 35 healthy individuals) was used to elicit multiple effects associated with changes in autonomic drive as well as blood gases including hypercapnia. The LDV pulse was obtained from two sites overlying the carotid artery, separated by 40 mm. A robust pulse signal was obtained from both sites, in accord with the well-described changes in carotid diameter over the blood pressure cycle. Emphasis was placed on extracting timing measures from the LDV pulse, which could serve as surrogate measures of pulse wave velocity (PWV) and the associated arterial stiffness. For validation purposes, a standard measure of pulse transit time (PTT) to the radial artery was obtained using a tonometric sensor. Two key measures of timing were extracted from the LDV pulse. One involved the transit time along the 40 mm distance separating the two LDV measurement sites. A second measure involved the timing of a late feature of the LDV pulse contour, which was interpreted as reflection wave latency and thus a measure of round-trip travel time. Both LDV measures agreed with the conventional PTT measure, in disclosing increased PWV during periods of active rebreathing. These results thus provide additional evidence that measures based on the non-contact LDV technique might provide surrogate measures for those obtained using conventional, more obtrusive assessment methods that require attached sensors.

Frontal P300 decrements, alcohol dependence, and antisocial personality disorder.

BACKGROUND: The purpose of this study was to examine the independent and interactive effects of alcohol dependence, antisocial personality disorder (ASPD), and age on brain function. METHODS: P300 event-related potentials (ERPs) were recorded from 393 alcohol-dependent and 170 non-alcohol-dependent adults while they performed a visual oddball task. The two subject groups were further subdivided based upon age and the presence/absence of ASPD. RESULTS: Alcohol dependence was associated with a significant P300 amplitude decrement at anterior electrode sites only. Antisocial personality disorder was also associated with reduced P300 amplitudes at anterior electrode sites; however, the effects were only significant among subjects 30 years of age or younger. To validate this association between ASPD and P300 amplitude a correlational analysis was performed; the correlation between anterior P300 amplitude and the total number of childhood conduct disorder and adult ASPD symptoms was significant. CONCLUSIONS: The P300 amplitude decrement found at anterior electrode sites among subjects with ASPD is consistent with the results of numerous ERP, neuroimaging, or neuropsychologic studies of anterior brain function. Our study is unique in suggesting that the effects of ASPD on anterior brain function are best detected during early adulthood. The study also suggests that the detrimental neurophysiologic effects of alcohol dependence predominantly involve the anterior brain.

Altered brain development in Turner's syndrome: an event-related potential study.

We compared event-related brain potentials (ERPs) and reaction time (RT) measures from untreated young (prepubertal and peripubertal; ages 9 to 14) and old (postpubertal; ages 15 to 20) Turner's syndrome (TS) subjects with those from normal age-matched controls. Comparisons among groups permitted the assessment of the relative roles of congenital and maturational brain alterations as possible bases of the cognitive deficits in TS. All subjects were presented with series of auditory stimuli, and they either counted one of the two stimuli or made rapid discriminative button presses to both. The results indicated that, whereas the ERPs in young TS females were essentially the same as those in their age-matched controls, the ERPs in old TS females more closely resembled those in both young groups than those in their age-matched controls. Specifically, a late (400 to 900 msec) frontal negative slow wave (Nc) in the old TS subjects failed to show the normal maturational course in which the amplitude and duration of this component steadily decreases with age. Except for slightly greater amounts of N1 amplitude in the young TS group, the latencies, amplitudes, and scalp distributions of the other ERP components (N1, P2, N2, P300) were all the same at all ages in the TS subjects and their controls. Behaviorally, both TS groups had longer RTs than their controls but, consistent with the ERP results, they did not make more errors.(ABSTRACT TRUNCATED AT 250 WORDS)

Case of direct insertion within a chromosome 3 leading to a chromosome 3p duplication in an offspring.

An infant with developmental delay and multiple minor congenital anomalies had a duplication of bands p11.1----p14.2 in 3p. Maternal chromosome studies demonstrated a direct intrachromosomal insertion within chromosome 3p.

Heritability of event-related brain potentials in families with a history of alcoholism.

Event-related brain potentials (ERPs) are altered in patients with a variety of psychiatric disorders and may represent quantitative correlates of disease liability that are more amenable to genetic analysis than disease status itself. Estimates of heritability are presented for amplitude and latency of the N1 and P3 components of the ERP measured at 19 scalp locations in response to visual and auditory stimuli for 604 individuals in 100 pedigrees ascertained as part of the Collaborative Study on the Genetics of Alcoholism. Significant heritabilities were found for visual P3 amplitude in response to all stimuli and for visual P3 latency in response to target and novel, but not non-target, stimuli. Heritability of visual N1 latencies was uniformly low, whereas heritability of visual N1 amplitude was significant for all electrodes in response to the non-target stimuli but only for posterior electrodes in the other two stimulus conditions. Heritabilities for auditory target P3 were similar to those of the visual stimuli, with auditory target P3 amplitudes and latencies both demonstrating significant heritability. For auditory P2 in response to non-target stimuli, peak amplitude was heritable, but latency was not. Auditory N1 amplitude and latency were significantly heritable for both target and non-target conditions and did not demonstrate the anterior/posterior patterning obtained for visual N1 amplitude. This study represents the first systematic assessment of heritability of these potential neurophysiological markers in families with a history of alcoholism and suggests that many of these ERP phenotypes have heritabilities strong enough to justify genomic screening for loci jointly influencing ERP abnormalities and liability to alcoholism.

Relationship of genetically transmitted alpha EEG traits to anxiety disorders and alcoholism.

We tested the hypothesis that a heritable EEG trait, the low voltage alpha (LV), is associated with psychiatric disorders. Modest to moderate evidence for genetic linkage of both panic disorder and the low voltage alpha trait to the same region of chromosome 20q has recently been reported, raising the issue of whether there is a phenotypic correlation between these traits. A total of 124 subjects including 50 unrelated index subjects and 74 relatives were studied. Alpha EEG power was measured and EEG phenotypes were impressionistically classified. Subjects were psychiatrically interviewed using the SADS-L and blind-rated by RDC criteria. Alcoholics were four times more likely to be LV (including so-called borderline low voltage alpha) than were nonalcoholic, nonanxious subjects. Alcoholics with anxiety disorder are 10 times more likely to be LV. However, alcoholics without anxiety disorder were similar to nonalcoholics in alpha power. An anxiety disorder (panic disorder, phobia, or generalized anxiety) was found in 14/17 LV subjects as compared to 34/101 of the rest of the sample (P < 0.01). Support for these observations was found in the unrelated index subjects in whom no traits would be shared by familial clustering. Lower alpha power in anxiety disorders was not state-dependent, as indicated by the Spielberger Anxiety Scale. Familial covariance of alpha power was 0.25 (P < 0.01). These findings indicate there may be a shared factor underlying the transmissible low voltage alpha EEG variant and vulnerability to anxiety disorders with associated alcoholism. This factor is apparently not rare, because LV was found in approximately 10% of unrelated index subjects and 5% of subjects free of alcoholism and anxiety disorders.

Alcohol intoxication reduces visual sustained attention.

Effects of alcohol intoxication on visual sustained attention were studied using a vigilance task entailing detection of degraded target stimuli. Data were obtained in separate sessions under four ethanol doses, ranging from 0 (placebo) to 1.05 g/kg lean body weight, with periodic maintenance dosing of 0.12 g/kg. Intoxication lowered the overall level of detection performance, and in addition produced dose-related increases in the rate of performance decrement over time. Analysis of performance data using techniques derived from Signal Detection Theory indicated that the decrements were due specifically to alterations in perceptual sensitivity. Examination of eye movements and blinks indicated that the effects of ethanol were not mediated peripherally. Rather, alcohol appears to have deleterious effects on central processing capacity and the availability of capacity over time. The alcohol-related failure of sustained attention may contribute to increased accident risk in tasks requiring continuous performance.

The P300 brain potential is reduced in smokers.

RATIONALE: Tobacco smoking is the most prevalent type of substance abuse, yet its biobehavioral etiology is little understood. Identification of differences between smokers and non-smokers on basic characteristics of neurocognitive functioning may help to elucidate the mechanisms of tobacco dependence. OBJECTIVES: This study assessed the relationship between smoking status and the P300 component of event-related potential (ERP) while controlling for potential confounders such as alcoholism, drug abuse, and psychopathology. METHODS: The ERP responses elicited by a visual oddball task were measured at the mid-parietal site in 905 current smokers, 463 ex-smokers, and 979 never smokers. RESULTS: P300 amplitude was significantly lower in current cigarette smokers compared to never-smokers. Ex-smokers did not differ significantly from never-smokers. P300 reduction was also associated with alcoholism, drug dependence, and family density of alcoholism. However, after controlling for smoking, only family density of alcoholism remained a significant predictor of P300 amplitude. CONCLUSIONS: The results indicate a significant effect of smoking status on P300 amplitude which is additive to family history of alcoholism and suggest that either (1) long-term tobacco smoking may produce a reversible change in brain function, or (2) reduced P300 may be a marker of risk for nicotine dependence.

Event-related perturbations in an electrophysiological measure of auditory function: a measure of sensitivity during orienting?

The effects of salient foreground stimuli in evoked potentials to weak background probe stimuli were examined in situations requiring passive observation or discriminative judgments of foreground tone stimuli. The background probe stimuli consisted of a continual train of weak acoustic stimuli presented at a rate of about 40 stimuli per second. Under such conditions, a 40-Hz steady-state rhythm (SSR) is established, which has been proposed to consist of the algebraic summation of individual middle-latency components evoked by stimuli in the train. The 40-Hz SSR was averaged over trials and extracted from the composite event-related potential signal using narrow-band digital filtering, for continuous examination of latency and amplitude during the course of the period immediately preceding and following the foreground stimulus. The foreground stimulus was followed by a brief period (peaking at about 200 ms) during which the latency of response to the background probe stimuli was reduced. The extent of this latency reduction was in proportion to the magnitude of the simultaneous slow-wave ERP responses and, to a lesser extent, heart rate responses. It is proposed that the results may reflect a transient period of sensitization during orienting, at a presumably early level in the auditory system, and that the method thus offers a means for determining the extent and temporal course of such effects.

Visual P300 and the self-directedness scale of the Temperament and Character Inventory.

Reduced amplitude of the P300 event-related brain potential has been associated with several psychopathological conditions and is thought to represent brain dysfunction in such conditions. Predisposition to personality disorders and psychopathology in general is also associated with low scores on the self-directedness (SD) scale of the Temperament and Character Inventory. The present preliminary study investigated the relationship between amplitudes of P300 elicited by rare target stimuli in a visual oddball task and SD scores in 58 healthy participants. P300 was found to be significantly reduced in subjects with low SD, as supported by correlational analysis and by comparison of groups formed on the basis of SD scores. This finding may be relevant to prior findings indicating reduced P300 amplitudes in a variety of psychopathological conditions and suggests that a common vulnerability factor, reflected in the low SD personality scores, may contribute to the P300 reduction in psychiatric populations.

Decreased cingulate and precuneate glucose utilization in alcoholic Korsakoff's syndrome.

Localized cerebral glucose utilization was determined for nine abstinent alcoholic men with Korsakoff's syndrome and 10 age-matched normal men who underwent positron emission tomography with [18F]2-fluoro-2-deoxyglucose (FDG). Patients with Korsakoff's syndrome showed relatively decreased glucose utilization in cingulate and precuneate areas. These decreases persisted even after correction for group differences in ventricular and sulcal cerebrospinal fluid measured on computed tomography. Electroencephalographic recordings at the time of FDG uptake showed no group differences, a finding that demonstrates that the metabolic differences could not be explained by differences in physiological arousal at the time of scanning. It is concluded that the decreased glucose utilization in the patients reflects a disruption of memory circuitry, the Papez circuit, caused by diencephalic lesions induced by thiamine deficiency.

Event-related perturbations in an electrophysiological measure of auditory sensitivity: effects of probability, intensity and repeated sessions.

It is often held that novel or salient stimuli are followed by a brief period of orienting or alerting during which sensory processes are facilitated. Evidence for such a period of facilitation was sought in a paradigm in which evoked responses to weak auditory probe stimuli were examined when given in the presence of salient foreground stimuli, which were varied in probability and intensity, and which were given in two replicate sessions. The background probe stimuli consisted of a continuous train of auditory pip stimuli delivered at a rate of 40 pips per second. Under such conditions of repetitive stimulation a steady-state rhythm (SSR), which is believed to reflect summated early and middle latency evoked responses, is established in the EEG at a corresponding frequency of 40 Hz. The 40 Hz SSR was extracted using a digital averaging and filtering technique and examined continuously for changes in amplitude and latency. The rhythm showed a brief episode during which the latencies of response were decreased. The reduction in latency was greatest at 186 ms after the foreground stimulus, at which time the latencies of individual peaks in the rhythm were reduced by about 3.5 ms. The magnitude of the latency reduction response was larger for intense and for rare stimuli, and showed long-term decrement during the second session. Event-related potential and heart rate responses to the foreground stimulus were also affected by probability, intensity and session, but not in the same pattern. It was hypothesized that the latency shift in the 40 Hz SSR reflects a brief period of sensitization during alerting or orienting responses.

Slow brain potentials in a visual-spatial memory task: topographic distribution and inter-laboratory consistency.

Slow brain electrical potentials (SPs) were investigated in a visual-spatialmemory task. Two issues were addressed: (1) the nature and topographic distribution of the potentials obtained under such conditions; and (2) the consistency of the SPs when recorded in six identically configured laboratories. Fifteen young male subjects were studied at each laboratory (total n = 90). The paradigm entailed presentations of paired-visual patterns (S1 and S2), to which subjects responded with a choice reaction time response indicating whether or not the two patterns matched. A biphasic contingent negative variation (CNV) was produced which consisted of an early symmetric component with bilateral foci at posterior temporal sites and a subsequent mid-parietal dominant wave later in the retention interval. Although the CNVs from all laboratories were similar in waveform and in topographic distribution, there were significant inter-laboratory differences in amplitude of the slow potential components. The topographic distributions of the components and the possible role of sampling effects are discussed.

P300 from an auditory oddball task: inter-laboratory consistency.

Event-related potentials (ERPs) were recorded from normal subjects for the purpose of evaluating measurement consistency among six laboratories located in different cities within the United States. At each laboratory location 15 male subjects were tested using a simple auditory stimulus discrimination task and identical electrophysiological equipment and recording methods. Assessment of the N1, P2, N2, and P3(00) potentials from both the target and standard stimuli resulted in no reliable differences among laboratories for component amplitudes, latencies, and scalp distributions. Quantitative evaluation of overall waveform and specific component morphology yielded good to excellent agreement across laboratories. The findings suggest that large-scale inter-laboratory human electrophysiological studies are feasible and may prove of value when using ERPs to evaluate cognitive function in humans.

Hemispheric differences for P300 amplitude from an auditory oddball task.

The P3(00) event-related potential (ERP) was elicited in 80 normal, right-handed male subjects using a simple auditory stimulus discrimination task, with electroencephalographic (EEG) activity recorded at 19 electrodes. P300 amplitude was larger over the right compared to left hemisphere electrode sites primarily at anterior-medial locations (F3/4, C3/4) for both target and standard stimuli. The N100, P200, and N200 components also demonstrated several similar, albeit less robust, hemispheric asymmetries. No hemispheric effects for P300 latency were observed, with few consistent latency findings for any of the other components obtained. The results suggest that the discrimination process underlying P300 generation may originate with right frontal activation.

Visual P300: an interlaboratory consistency study.

The P300 component of the event-related potential is reduced in both abstinent alcoholics and in males at high risk for developing alcoholism. Here, 96 males (mean = 22.1 years) who were part of an interlaboratory (n = 6) consistency study in the national COGA (Collaborative Study on the Genetics of Alcoholism) Project were subjects in a visual target selection paradigm. Each of the participating laboratories used the same experimental design, hardware and software. Each subject received a randomized series of target, nontarget and novel visual stimuli, and upon detecting the target stimulus, was required to make a button press as quickly as possible. Statistical analyses indicated that there were no significant differences in P300 amplitude and latency at the Pz electrode under any of the aforementioned conditions across laboratories. Thus, the interlaboratory consistency of the visual P300 indicates that it may be of utility in a national collaborative study on the genetics of alcoholism.

Dose-related effects of ethanol on visual sustained attention and event-related potentials.

The effects of acute ethanol intoxication on visual sustained attention were investigated in male social drinkers. Four doses ranging from 0 (placebo) to 1.05 g/kg lean body weight, with periodic maintenance dosing of 0.12 g/kg, were given in separate sessions. The task required subjects to monitor a series of blurred digits presented singly at a rate of one per sec and to respond to occasional (p = 0.25) target digits with a speeded button press. Detection performance deteriorated as a function of both dose and time on task. In addition, the factors of dose and time on task interacted to produce a more rapid performance decrement under the higher doses. Early event-related potential (ERP) components (N1 and P2) were not greatly affected, suggesting that the performance decrement reflects central rather than peripheral factors. Later components related to cognitive appraisal processes (N2, P3), in contrast, varied in both amplitude and latency. Ethanol yielded dose-related delays in N2 and P3 latencies, which paralleled reaction time increases. The amplitude of N2 also decreased over time on task, and P3 amplitude decreased both as a function of dose and time on task. ERP and performance data were interpreted as demonstrating an adverse effect of ethanol on central processing capacity.