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.

Alcohol use disorders and anxiety disorders: relation to the P300 event-related potential.

BACKGROUND: The robust association of alcoholism with reduced P300 event-related potential amplitude has been largely established in severely affected alcoholics and their offspring. Few studies have examined the relationship of increased arousal, anxiety, and P300. In this study, we sought to determine whether P300 group differences could be discerned in well functioning individuals with less severe forms of alcohol use disorders and anxiety disorders. We were particularly interested in looking at the subgroup of alcohol use disorders accompanied by anxiety disorders. This subgroup has previously been found to have diminished alpha amplitude in the resting EEG. METHODS: Male and female community volunteers (99 unrelated index participants and 78 relatives) and 21 unrelated volunteers from an anxiety disorder clinic were interviewed by using the Schedule for Affective Disorders and Schizophrenia, Lifetime version. Blind-rated lifetime psychiatric diagnoses were assigned according to DSM-III-R criteria. Auditory and visual P300 event-related potentials were elicited with an oddball paradigm and were recorded at the midparietal (Pz) site. RESULTS: As expected, auditory P300 amplitudes were significantly reduced in participants with alcohol use disorders and significantly increased in participants with lifetime anxiety disorders. However, more detailed analysis revealed that, in an apparent paradox, auditory P300 amplitudes were lowest in individuals with comorbid alcohol use and anxiety disorders and highest in individuals with anxiety disorders alone. Visual P300 amplitudes followed the same trends but were generally not significant. CONCLUSIONS: Even in a sample of largely community-ascertained individuals, auditory P300 amplitude is reduced in alcoholics, particularly those with anxiety disorders, and is highest in nonalcoholics with anxiety disorders.

An integrative approach for studying the etiology of alcoholism and other addictions.

Studies of alcoholism etiology often focus on genetic or psychosocial approaches, but not both. Greater understanding of the etiology of alcohol, tobacco and other addictions will come from integration of these research traditions. A research approach is outlined to test three models for the etiology of addictions--behavioral undercontrol, pharmacologic vulnerability, negative affect regulation--addressing key questions including (i) mediators of genetic effects, (ii) genotype-environment correlation effects, (iii) genotype x environment interaction effects, (iv) the developmental unfolding of genetic and environmental effects, (v) subtyping including identification of distinct trajectories of substance involvement, (vi) identification of individual genes that contribute to risk, and (vii) the consequences of excessive use. By using coordinated research designs, including prospective assessment of adolescent twins and their siblings and parents; of adult substance dependent and control twins and their MZ and DZ cotwins, the spouses of these pairs, and their adolescent offspring; and of regular families; by selecting for gene-mapping approaches sibships screened for extreme concordance or discordance on quantitative indices of substance use; and by using experimental (drug challenge) as well as survey approaches, a number of key questions concerning addiction etiology can be addressed. We discuss complementary strengths and weaknesses of different sampling strategies, as well as methods to implement such an integrated approach illustrated for the study of alcoholism etiology. A coordinated program of twin and family studies will allow a comprehensive dissection of the interplay of genetic and environmental risk-factors in the etiology of alcoholism and other addictions.

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.

Genetics of event-related brain potentials in response to a semantic priming paradigm 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. Results of a genomewide linkage screen are presented for amplitude of the N4 and P3 components of the ERP, measured at 19 scalp locations in response to a semantic priming task for 604 individuals in 100 pedigrees ascertained as part of the Collaborative Study on the Genetics of Alcoholism. N4 and P3 amplitudes in response to three stimuli (nonwords, primed words [i.e., antonyms], and unprimed words) all showed significant heritabilities, the highest being.54. Both N4 and P3 showed significant genetic correlations across stimulus type at a given lead and across leads within a stimulus, indicating shared genetic influences among the traits. There were also substantial genetic correlations between the N4 and P3 amplitudes for a given lead, even across stimulus type. N4 amplitudes showed suggestive evidence of linkage in several chromosomal regions, and P3 amplitudes showed significant evidence of linkage to chromosome 5 and suggestive evidence of linkage to chromosome 4.

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.

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.

Factors associated with falling asleep at the wheel among long-distance truck drivers.

Data on the prevalence and hypothesized predictors of falling asleep while driving were gathered through face-to-face interviews with 593 long-distance truck drivers randomly selected at public and private rest areas and routine roadside truck safety inspections. Hypothesized predictor variables related to drivers' typical work and rest patterns, extent of daytime and night-time drowsiness, symptoms of sleep disorder, measures of driving exposure, and demographic characteristics. A sizeable proportion of long-distance truck drivers reported falling asleep at the wheel of the truck: 47.1% of the survey respondents had ever fallen asleep at the wheel of a truck, and 25.4% had fallen asleep at the wheel in the past year. Factor analysis reduced the large set of predictors to six underlying, independent factors: greater daytime sleepiness; more arduous schedules, with more hours of work and fewer hours off-duty; older, more experienced drivers; shorter, poorer sleep on road; symptoms of sleep disorder; and greater tendency to night-time drowsy driving. Based on multivariate logistic regression, all six factors were predictive of self-reported falling asleep at the wheel. Falling asleep was also associated with not having been alerted by driving over shoulder rumble strips. The results suggest that countermeasures that limit drivers' work hours and enable drivers to get adequate rest and that identify drivers with sleep disorders are appropriate methods to reduce sleepiness-related driving by truck drivers.

Genetic differences in alcohol sensitivity and the inheritance of alcoholism risk.

BACKGROUND: Substantial evidence exists for an important genetic contribution to alcohol dependence risk in women and men. It has been suggested that genetically determined differences in alcohol sensitivity may represent one pathway by which an increase in alcohol dependence risk occurs. METHODS: Telephone interview follow-up data were obtained on twins from male, female and unlike-sex twin pairs who had participated in an alcohol challenge study in 1979-81, as well as other pairs from the same Australian twin panel surveyed by mail in 1980-82. RESULTS: At follow-up, alcohol challenge men did not differ from other male twins from the same age cohort on measures of lifetime psychopathology or drinking habits; but alcohol challenge omen were on average heavier drinkers than other women. A composite alcohol sensitivity measure, combining subjective intoxication and increase in body-sway after alcohol challenge in 1979-81, exhibited high heritability (60 %). Parental alcoholism history was weakly associated with decreased alcohol sensitivity in women, but not after adjustment for baseline drinking history, or in men. High alcohol sensitivity in men was associated with substantially reduced alcohol dependence risk (OR = 0.05, 95% CI 0.01-0.39). Furthermore, significantly decreased (i.e. low) alcohol sensitivity was observed in non-alcoholic males whose MZ co-twin had a history of alcohol dependence, compared to other non-alcoholics. These associations remained significant in conservative analyses that controlled for respondents' alcohol consumption levels and alcohol problems in 1979-81. CONCLUSIONS: Men (but not women) at increased genetic risk of alcohol dependence (assessed by MZ co-twin's history of alcohol dependence) exhibited reduced alcohol sensitivity. Associations with parental alcoholism were inconsistent.

Association of low-voltage alpha EEG with a subtype of alcohol use disorders.

BACKGROUND: Neurophysiological traits may identify more homogeneous subgroups of alcoholics. Such discoveries could yield information regarding pathophysiological development, leading to more specific preventive measures and treatments. In an earlier study of 127 individuals, 59 of whom were unrelated, we found that a heritable resting Electroencephalographic (EEG) phenotype, i.e., the low-voltage alpha (LVA) trait, was associated with alcohol use disorders and anxiety disorders. METHODS: We evaluated these findings using an independent, similarly established, dataset of 120 subjects. We also extended the study to a larger set of 149 unrelated individuals from a total sample of 247 subjects for whom psychiatric diagnoses and resting EEG phenotypes were available. Blind-rated psychiatric diagnoses were formulated according to DSM-III-R criteria. RESULTS: In the replication sample, the LVA trait was again more common among subjects with anxiety disorders than among those without. In the total group of unrelated individuals, alcoholics were significantly (3 times) more likely to show the LVA trait than were nonalcoholics. Again, individuals with anxiety disorders were significantly (3 times) more likely to exhibit the LVA trait than were those without anxiety disorders. Of 11 unrelated alcoholics with anxiety disorders, seven showed the LVA trait. It was specifically the LVA trait and not low-amplitude alpha activity that was associated with alcohol use disorders. CONCLUSIONS: The results of this replication study and the analysis of the total sample of unrelated individuals support an association between LVA EEG and the subtype of alcohol use disorders associated with anxiety disorders. The LVA phenotype may be a vulnerability factor for alcohol use disorders and anxiety disorders.

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.

Amplitude of visual P3 event-related potential as a phenotypic marker for a predisposition to alcoholism: preliminary results from the COGA Project. Collaborative Study on the Genetics of Alcoholism.

Recent data collected at six identical electrophysiological laboratories from the large national multisite Collaborative Study on the Genetics of Alcoholism provide evidence for considering the P3 amplitude of the event-related potential as a phenotypic marker for the risk of alcoholism. The distribution of P3 amplitude to target stimuli at the Pz electrode in individuals 16 years of age and over from 163 randomly ascertained control families (n = 687) was compared with those from 219 densely affected alcoholic families (n = 1276) in which three directly interviewed first-degree relatives met both DSM-III-R and Feighner criteria at the definite level for alcohol dependence (stage II). The control sample did not exclude individuals with psychiatric illness or alcoholism to obtain incidence rates of psychiatric disorders similar to those of the general population. P3 amplitude data from control families was converted to Z-scores, and a P3 amplitude beyond 2 SD's below the mean was considered an "abnormal trait." When age- and sex-matched distributions of P3 amplitude were compared, members of densely affected stage II families were more likely to manifest low P3 amplitudes (2 SD below the mean) than members of control families, comparing affected and unaffected offspring, and all individuals; all comparisons of these distributions between groups were significant (p < 0.00001). P3 amplitude means were also significantly lower in stage II family members, compared with control family members for all comparisons, namely probands, affected and unaffected individuals (p < 0.0001), and offspring (p < 0.01). Furthermore, affected individuals from stage II families, but not control families, had significantly lower P3 amplitudes than unaffected individuals (p < 0.001). Affected males from stage II families had significantly lower P3 amplitudes than affected females (p < 0.001). Recent linkage analyses indicate that visual P3 amplitude provides a biological phenotypic marker that has genetic underpinnings.

Quantitative trait loci analysis of human event-related brain potentials: P3 voltage.

The P3 event-related brain potential (ERP) is a positive-going voltage change of scalp-recorded electroencephalographic activity that occurs between 300-500 ms after stimulus onset. It is elicited when a stimulus is perceived, memory operations are engaged, and attentional resources are allocated toward its processing. Because this ERP component reflects fundamental cognitive processing, it has found wide utility as an assessment of human mental function in basic and clinical studies. In particular, P3 attributes are heritable and have demonstrated considerable promise as a means to identify individuals at genetic risk for alcoholism. We have conducted a quantitative linkage analysis on a large sample from families with a high density of affected individuals. The analyses suggest that several regions of the human genome contain genetic loci related to the generation of the P3 component of the ERP, which are possible candidate loci underlying the functional organization of human neuroelectric activity.

P300 topography of amplitude/latency correlations.

The correlational association from 19 electrode sites between peak amplitude and latency for the P3(00) event-related brain potential (ERP) for n = 80 homogeneous subjects was assessed using a simple auditory discrimination task. The correlation strength varied systematically across scalp topography in different ways for the various ERP components. For the target stimuli, P3 amplitude and latency were negatively correlated and most tightly coupled over the frontal-central and right medial/lateral recording sites. In contrast, the N1 produced negative correlations that were strongest over the left and right central/lateral locations; P2 demonstrated a positive correlation that was strongest frontally and centrally; N2 demonstrated a positive correlations that was strongest over the central and parietal sites. ERPs from the standard stimuli produced generally similar patterns for the P3 and P2 components, with only weak or no reliable effects observed for the N1 and N2 potentials. Taken together, the findings suggest that analysis of amplitude/latency correlational relationships can provide information about ERP component generation. Theoretical implications are discussed.

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.

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.

Nonketotic hyperglycinemia: atypical clinical and biochemical manifestations.

A 16-year-old boy had intermittent chorea, delirium, and vertical gaze palsy precipitated by febrile illness. Nonketotic hyperglycinemia was confirmed by measurement of liver and lymphoblast glycine cleavage enzyme activity. Deficient but residual enzyme activity was demonstrated in both tissues, possibly accounting for the mild phenotype. Confirmation of an atypical variant of nonketotic hyperglycinemia with residual glycine cleavage enzyme activity has important implications for diagnosis and treatment.

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.

P300 hemispheric amplitude asymmetries from a visual oddball task.

The P3(00) event-related potential (ERP) was elicited in 80 normal, right-handed male subjects using a simple visual discrimination task, with electroencephalographic (EEG) activity recorded at 19 electrodes. P3 amplitude was larger over the right than over the left hemisphere electrode sites primarily at anteromedial locations (F3/4, C3/4) for target, novel, and standard stimuli. The N1, P2, and N2 components also demonstrated hemispheric asymmetries. The strongest P3 hemispheric asymmetries for all stimuli were observed at anterior locations, suggesting a frontal right hemisphere localization for initial stimulus processing, although target stimuli produced larger P3 amplitudes at parietal locations that did novel stimuli. The relationships of hemispheric asymmetries to anatomical variables, background EEG activity, and neurocognitive factors are discussed.