Event-related potential evidence for frontal cortex effects of chronic cocaine dependence.

We examined the effects of cocaine dependence and cocaine and alcohol codependence on the P3A event-related potential component. Ten chronic cocaine-dependent subjects, 10 chronic cocaine and alcohol codependent subjects, and 20 controls were studied in an auditory paradigm that included target, nontarget, and novel rare nontarget conditions. Substance-dependent subjects were abstinent from cocaine and/or alcohol for 2-6 weeks. Eighteen of these subjects (4 chronic cocaine-dependent subjects, 4 chronic cocaine/alcohol codependent subjects, and 10 normal controls) were also studied in an analogous visual paradigm. In the auditory modality, the latency of the P3A response in the novel rare nontarget condition was delayed and its amplitude was reduced in both substance-dependent samples compared to controls. Comparable results were found for the smaller samples studied in the visual modality. These results suggest that chronic cocaine dependence produces deficits in frontal cortex functions.

Delayed latency of the event-related brain potential P3A component in HIV disease. Progressive effects with increasing cognitive impairment.

OBJECTIVE: To examine the degree to which P3A latency was sensitive to the early and progressive effects of human immunodeficiency virus (HIV) disease on frontal cortex function by studying HIV-positive subjects who varied in degree of cognitive impairment. DESIGN: Event-related brain potential studies of four groups of subjects: cognitively nonimpaired high-risk HIV-negative subjects, cognitively nonimpaired HIV-positive subjects, cognitively mildly to moderately impaired HIV-positive subjects, and cognitively severely impaired HIV-positive subjects. SETTING: Voluntarily participating subjects on an outpatient basis at a medical center facility. PARTICIPANTS: Seventy-one community-residing gay or bisexual HIV-positive male volunteers were compared with 17 HIV-negative male gay or bisexual subjects used as a control sample. The HIV-positive subjects were stratified with regard to severity of cognitive impairment into the following three subsamples: subjects who were cognitively normal (n = 35), subjects with mild to moderate cognitive impairment (n = 20), and subjects with severe cognitive impairment (n = 16), with the samples closely matched in age. The HIV-positive subsamples were closely matched on percentage of CD4 lymphocytes. Subjects were excluded if they reported a history of drug or alcohol abuse, a major mental disorder, a head injury with loss of consciousness, or brain disease other than HIV related. MAIN OUTCOME MEASURE: P3A latency. RESULTS: P3A latency was significantly delayed in HIV-positive subjects compared with HIV-negative control subjects, with a delay of 12 milliseconds in the cognitively normal group (P < .02) and the magnitude of delay increasing with increasing severity of HIV-associated cognitive impairments (P < .001). Delayed P3A was primarily associated with the progression of HIV-associated cognitive impairment, with a secondary and additive association with severity of HIV-associated medical illness. CONCLUSION: This finding suggests that delayed P3A latency is sensitive to the relatively early central nervous system effects of HIV and progresses with worsening of the central nervous system effects of HIV.

Delayed P3A in abstinent elderly male chronic alcoholics.

Significant central nervous system toxicity in frontal brain regions has been demonstrated with chronic alcohol consumption both on autopsy and using neuropsychological testing. This study examined the latency of an objective and reproducible brain event-related potential measure of frontal cortex function in chronic elderly male alcoholics who were abstinent 3 months-2 years, a patient group in whom the central nervous system effects of chronic alcohol abuse are thought to be largest and most persistent. We examined the latency of the P3A event-related potential component, which reflects a frontal maximum orienting response to novel stimuli. Twelve elderly abstinent chronic alcoholic males and 11 elderly male controls were studied in an auditory and a visual paradigm, each of which included target, nontarget, and novel rare nontarget conditions. In both modalities, the P3A response to the novel rare nontarget stimuli was significantly delayed in the chronic alcoholics. P3B delays to the target stimuli were also present in the alcoholics, with the P3A and P3B effects being independent of each other. For both P3A and P3B, the effects were larger and more consistent in the visual compared with the auditory modality. Our conclusions are as follows: (1) both P3A and P3B latency delays are evident in elderly abstinent chronic alcoholics; (2) separate mechanisms are responsible for these effects; (3) these effects are more sensitively detected in the visual versus the auditory modality; and (4) delayed P3A latency may be an objective and reproducible index of the frontal cortex effects of chronic alcohol abuse.

Alcohol abuse and HIV infection have additive effects on frontal cortex function as measured by auditory evoked potential P3A latency.

Both alcohol and human immunodeficiency virus (HIV) infection have been shown to produce central nervous system (CNS) morbidity in frontal brain regions. The degree to which the CNS morbidity in HIV infection, as it affects frontal cortex function, may be preferentially increased by alcohol abuse was examined using the auditory P3A evoked potential. The P3A indexes an orienting response, maximal over frontal cortex that occurs when novel nontarget stimuli are presented in the midst of a target detection paradigm. Four groups of subjects were compared: HIV+ alcohol abusers, HIV+ light/nondrinkers, HIV- alcohol abusers, and HIV- light/nondrinkers. The alcohol abuser and light/nondrinker HIV+ groups were matched on percent CD4 lymphocytes, insuring that the results reflected specific CNS effects and were not a result of differences between the groups in the degree of systemic immune suppression. Alcohol abuse and HIV infection had at least additive effects on P3A latency, consistent with alcohol abuse worsening the effect of HIV disease on frontal cortex function. Post-hoc analyses suggested that concomitant alcohol abuse results in the effects of HIV infection on P3A latency becoming manifest earlier in the HIV disease process.

Frequency domain dipole localization: extensions of the method and applications to auditory and visual evoked potentials.

We describe a statistical frequency domain approach to localizing equivalent dipole generators of human brain evoked potentials. The frequency domain representation allows considerable data reduction, constrains the magnitude function of the dipoles to be smooth, and accounts for the statistical properties of the background EEG. A previous paper described a restrictive model in which the dipole orientations were assumed to be fixed over time, and only one dipole was allowed. In this paper, we consider the more general model in which the orientation can vary over time, and which includes multiple dipole generators. The varying orientation model has the practical advantage of being more nearly linear and more flexible than the fixed orientation model, which facilitates convergence of the iterative fitting algorithm. We suggest a measure of goodness-of-fit that compares the likelihood of the dipole model with the likelihoods of saturated and null models. We report the results of fitting the model to recorded auditory and visual evoked potentials. A single dipole with fixed orientation seems to be an adequate model of the auditory midlatency response, while two dipoles with varying orientation are needed to fit the later P200 component. Analysis of the visual P100 response to unilateral stimulation localized a generator in the contralateral occipital cortex, as expected from anatomical considerations. A two-dipole model fit the visual P100 response of bilateral stimulations, and the locations of the two dipoles were similar to the locations obtained by single-dipole fits to the responses to left and right unilateral stimuli.

A controlled, longitudinal study of dementia in Parkinson's disease.

Serial assessments of cognition, mood, and disability were carried out at nine month intervals over a 54 month period on a cohort of 87 patients with Parkinson's disease (PD) and a matched cohort of 50 control subjects. Dementia was diagnosed from data by rigorously applying DSM-III-R criteria. Initially, 6% (5/87) PD patients were demented, compared with none of the 50 control subjects. A further 10 PD patients met the dementia criteria during the follow up period; this was equivalent, with survival analysis, to a cumulative incidence of 19%. With the number of person years of observation as the denominator, the incidence was 47.6/1000 person years of observation. None of the control subjects fulfilled dementia criteria during the follow up period. The patients with PD who became demented during follow up were older at onset of Parkinson's disease than patients who did not become demented, had a longer duration of Parkinson's disease, and were older at inclusion to the study.

Artifactually high coherences result from using spherical spline computation of scalp current density.

Coherence computed from common reference montages inextricably confounds true coherence with power and phase at the recording and reference electrodes. Direct measurement of coherence requires reference-free EEG data, such as data from EEG scalp current densities (SCDs), which estimate the potential gradient perpendicular to the scalp. Perrin et al. (1989) presented a method for computing SCDs by taking the Laplacian of the scalp potential surface generated by spherical spline interpolation. When this method of computing SCDs was applied to EEG data gathered from young adults, very high values were observed for inter-electrode coherences computed from the spherical spline derived SCD data but not from coherences computed from the common reference data. These high coherences prompted further examination of the properties of the spherical spline function and of spherical spline derived SCDs. Simulated data were constructed, and coherence was computed on the simulated data and on the SCDs derived from the spherical spline procedure and from the Hjorth (1980) procedure. The results of those simulations are presented, which demonstrate that a major artifact is introduced by using the spherical spline procedure. This artifact results from the spline weighting matrix used to derive the SCDs and strongly inflates the inter-electrode coherences of the SCD transformed data.

Motor, volitional and behavioural disorders in schizophrenia. 2: The 'conflict of paradigms' hypothesis.

An alternative to the conventional separation of extrapyramidal and catatonic symptoms exists in the 'conflict of paradigms' hypothesis, which proposes that there is a relative rather than absolute distinction between the two. The hypothesis predicts that a clinical association should exist between extrapyramidal and catatonic symptoms in schizophrenia. After rating 75 schizophrenic patients, a highly significant correlation between scores on the two classes of disorder was indeed found. This was composed of separate correlations between tardive dyskinesia and 'positive' catatonic phenomena, and Parkinsonism and 'negative' catatonic phenomena. The associations were not easily attributable to confounding factors and they were supported by factor analysis.

The cerebral laterality of mental image generation in normal subjects.

This research was an attempt to replicate and extend a published study that reported a left hemispheric locus for the generation of mental images. Several methodological problems were addressed, the stability of effects was assessed by repeating the experiment, and P300 latency was measured. A lateralized visual choice reaction time task was performed twice, once without the use of imagery and once with imagery. In each visual field, the use of imagery produced a speeding of reaction times when the target stimuli matched the image generated by the subject. A similar effect was present for P300 latency, and was still present in the reaction time data after partialling out the P300 latency effect. These results indicate that mental imagery can speed both stimulus evaluation and response processing. There was no difference in the amount of speeding for images in the two hemifields, providing no evidence for a preferential locus of mental image generation in either cerebral hemisphere.