Effects of ethanol, caffeine, and placebo on the auditory evoked response.

A previous paper (Wolpaw and Penry 1975) described separation of the 75-250 msec portion of the AER into N1P2, a product of large areas of cortex, and the T complex, probably a product of secondary auditory cortex. With monaural stimulation, the T complex is larger and earlier on the side contralateral to stimulation and on the right side. Thirty-one normal adults received 3 oz. of ethanol, 300 mg of caffeine, or placebo. Monaural AERs were recorded before intake in all cases, 1 and 4 h after ethanol and 80 min after caffeine or placebo. Blood levels of ethanol and caffeine were measured. Placebo produced mild (20%) decreases in N1P2 amplitude. Caffeine did not decrease N1P2 amplitude. It did produce a statistically significant 2% decrease in Ta peak latency. Ethanol reduced N1P2 amplitude markedly at 1 h and mildly at 4 h. Placebo did not affect hemispheric differences. Caffeine significantly increased the Ta peak ipsilateral vs. contralateral latency difference in 3 of 7 individuals. Ethanol significantly increased it in 3 of 6 subjects at 1 h and in 7 of 10 at 4 h, primarily by increasing ipsilateral latencies.     

Effects of a small dose of triazolam on P300

Ten healthy men (mean age, 33.9 years) participated in two experimental sessions cross-overed randomly in a double-blind manner: one with the placebo and another with 0.125 mg of triazolam (TRZ). Resting electroencephalography and event-related potential under oddball paradigm were recorded before the drug administration, and 1, 2, 4, 6 and 8 h after that. P300 waveforms were analyzed by peak amplitudes and 30-ms bin data. Triazolam may cause cognitive dysfunction without general sedation or apparent sleepiness, and this effect appeared 2 h, 4 h and 6 h, most prominently 6 h, after TRZ administration.     

Topographic mapping of cognitive event-related potentials in a double-blind, placebo-controlled study with the hemoderivative Actovegin in age-associated memory impairment

In a double-blind placebo-controlled study, the effects of Actovegin on cognitive event-related potentials were studied in 18 age-associated memory impairment (AAMI) patients. Actovegin is a protein-free metabolically active hemoderivative improving oxygen and glucose utilization. Each patient was treated, in randomized order, for 2 weeks with 250 ml 20% Actovegin and 250 ml placebo daily with an interval of 3 weeks in between. Psychophysiological tests were carried out by means of the Viennese Psychophysiological Test System (VPTS) before as well as 5 h after the administration of one single infusion on day 1 (acute effect), before (subacute effect) as well as after one additional superimposed infusion on day 15 (superimposed effect). There was no effect on earlier stages of information processing measured by N1 and P2 component of nontarget ERP nor on ERP latencies. However, P300 amplitude increased after acute, subacute as well as superimposed infusion of Actovegin as compared to placebo, confirming the hypothesis that nootropic drugs may influence the P300 amplitude in the sense of an improved availability of cognitive processing resources. This increase of P300 amplitude (up to 4.8 microV), seen specifically in central and parietal regions, proved to be significant in a confirmatory test.     

The effects of repetitive transcranial magnetic stimulation on depressive symptoms and the P(300) event-related potential

Changes in the Hamilton Depression Rating Scale and the P(300) auditory event-related potential were assessed in 10 patients with depression before and after a treatment course of five daily sessions of 10 Hz repetitive transcranial magnetic stimulation (rTMS) over the left prefrontal cortex. The patients were initially randomly allocated either to an active or a placebo rTMS treatment. All patients received both types of treatment separated by an interval of 4 weeks. The median Hamilton score decreased by 7 points following active rTMS and by 1 point after sham (p=0.075). Active rTMS was associated with a significant increase in the P(300) amplitude compared with sham (p=0.02). There was no correlation between changes in P(300) measurements and the Hamilton scores after active treatment. We conclude that five daily sessions of left prefrontal rTMS treatment is not of sufficient duration to make a significant improvement in depressive symptoms.     

Enhancement of heart rate variability by cholinergic stimulation with pyridostigmine in healthy subjects

The purpose of this study was to determine the effect of the oral administration of pyridostigmine bromide on indices of heart rate variability (HRV) in healthy young volunteers. Seventeen healthy participants (11 men, 6 women; aged 27 +/- 8 y) submitted to a randomized, crossover, double-blind protocol, in which they received 30 mg pyridostigmine bromide (PYR) or placebo orally at 8-hour intervals for 24 hours, on two separate days. Venous blood samples were collected 2 and 24 hours after the first dose for determination of serum cholinesterase activity. Holter tapes were recorded during the 24-hour period and analyzed using a semiautomatic technique to evaluate time- and frequency-domain indices of HRV and to build three-dimensional return maps for later quantification. Symptoms were mild and occurred similarly during administration of PYR and placebo (p = 0.140). Serum cholinesterase activity was reduced by 15% at 2 hours (p = 0.013) and by 14% at 24 hours (p = 0.010) after the first dose of PYR, but not after administration of placebo. Pyridostigmine administration caused a significant increase in the mean 24-hour R-R interval (placebo: 814 +/- 20 msec; PYR: 844 +/- 18 msec; p = 0.003) and in time-domain indices of HRV, such as the standard deviation of all R-R intervals (SDNN; placebo: 151 +/- 9 msec; PYR: 164 +/- 9 msec; p = 0.017), and the percentage of pairs of adjacent R-R intervals differing by more than 50 msec (pNN50; placebo: 12.8 +/- 1.8%; PYR: 13.9 +/- 1.5%; p = 0.029). Pyridostigmine had no significant effect on frequency-domain indices of HRV, but resulted in significant increase in P2, a parasympathetic index derived from the three-dimensional return map (placebo: 93 +/- 13 msec; PYR: 98 +/- 13 ms; p = 0.029). In conclusion, low-dose pyridostigmine reduced mean heart rate and increased HRV during a 24-hour period in healthy young subjects.     

Prestimulation-induced modulation of the P300 component of event related potentials accompanying startle in children

Positive EEG deflections with the latency and scalp distribution of the P300 accompany stratle in response to loud auditory stimuli in a non-task context. The purpose of this investigation is to determine of inhibitory and facilitatory prestimulation would have effects on the P300 similar to those on the startle blink. Prestimulation conditions were chosen to induce startle amplitude facilitation (4000 msec sustained tone), startle amplitude inhibition (120 msec prestimulation interval), and startle onset latency facilitation (60 msec prestimulation interval). Ninety-three boys (including normals and those with ADHD and/or enuresis) from a startle modulation study had EEG recordings of sufficient quality to provide data for the current study. Repeated measures analyses of variance demonstrated startle amplitude and P300 amplitude facilitation following the 4000 msec tone, startle amplitude and P300 amplitude inhibition following the 120 msec prestimulation interval, and startle onset latency and P300 peak latency facilitation (shorter latencies) following the 60 msec prestimulation interval. Hence, the vertex-recorded P300 elicited by startling stimuli was modulated by non-startling prestimulation in a manner that paralleled that of modulation of the brain-stem generated startle blink. Startle inhibition by prestimulation is mediated by an inhibitory pathway in the mesopontine lateral tegmentum. The brain-stem circuitry has a similar effect on the P300 even though the latter may be generated in more rostral strcutures. Alternatively, this automatically elicited P300 may represent a limbic or cortical reflection of the sensory processing taking place in the brain-stem. Either interpretation suggests a “bottom-up” as contrasted with a “top-down” mode of the sensory processing. This P300 obeys the rules of startle modulation by brain-stem mechanisms rather than indexing cortical evaluation of stimuli for task relevance, stimulus probability, and prior uncertainty.     

The effect of clonidine on auditory P300

Auditory evoked potential recordings were done on 14 normal subjects during baseline conditions as well as after oral administration of 0.2 mg of clonidine or placebo. P300 amplitude and latency measurements were obtained from 28 electrodes and analyzed. Clonidine resulted in a decrease in P300 amplitude, which was most marked in the occipital and left parieto-temporal regions. This effect was significant even after controlling for the sedative side effect of clonidine. P300 was unaffected by clonidine. These data suggest the possible use of clonidine-induced changes in P300 amplitude as an index of central noradrenergic responsiveness.     

Beneficial effects of thiamine on recognition memory and P300 in abstinent-cocaine dependent patients

The present study evaluated the effects of thiamine vs. placebo on memory task performance and event-related electroencephalographic potentials in eight abstinent cocaine-dependent patients. Patients orally ingested 5 g of thiamine and 5 g of a lactose placebo on two separate days scheduled approximately 1 week apart. The order of administration was randomized. Double-blind procedures were followed. Approximately 3 h after ingesting the capsules, patients completed Sternberg's (1975) memory scanning task during which performance and event-related potentials (P300) were recorded simultaneously. Thiamine was found to significantly improve recognition accuracy and P300 amplitude, at the midline parietal (Pz) electrode. The improvement was most reliable under conditions of increased memory load. These preliminary findings justify a further examination of the relation between thiamine's hypothesized effects on central nervous system cholinergic function, and the direct and indirect effects of cocaine abuse. ©1997 Elsevier Science Ireland Ltd.     

Long-term habituation of brain evoked potential responses and pituitary-adrenal secretion with repeated (placebo) testing

To study whether changes in late auditory evoked potentials (AF-Ps) and/or in stress-sensitive hormones of the hypothalamic—pituitary-adrenal (HPA) system take place between a first and a second placebo experiment and if so, whether these changes are possibly related to each other, we conducted two identical placebo sessions (2 ml 0.9% saline) and one cortisol session (50 mg) with 10 subjects on three different days. Plasma cortisol concentrations were significantly higher at the beginning of the first placebo experiment than the second, with a concordant decrease of plasma adrenocorticotropin hormone (ACTH) concentrations. In the AEP domain, a consistently lower P2 amplitude was observed in the first session. Since the change in late auditory processing could not be demonstrated after exogenous administration of cortisol, a direct mediation through an elevation of plasma cortisol concentrations or indirect mediation through a decrease of plasma ACTH concentrations seems unlikely. We rather propose that other stress-sensitive mechanisms, such as CCK, might account for the novelty-induced P2 amplitude lowering.     

Relation of a negative ERP component to response inhibition in a Go/No-go task.

Previous studies have suggested that a negative component (N2) of the event-related potential (ERP), whose peak latency is 200-300 msec after stimulus onset, may vary in amplitude depending on the neuronal activity required for response inhibition. To confirm this, ERPs were recorded in a Go/No-go paradigm in which subjects of one group (HI, n = 10) were asked to respond to Go stimuli with key pressing within a shorter period (less than 300 msec) than those of the other group (LI, n = 10) whose upper limit of the reaction time was relatively longer (less than 500 msec). All subjects had to withhold the Go response to the No-go stimuli without making overt muscle activities. The N2 component was recorded superposed on the initial descending limb of the P300 and other slow deflections, which were attenuated with a digital filter to measure the amplitude of N2. The N2 amplitude was significantly larger to the No-go stimulus than to the Go stimulus in both groups, but the N2 to the No-go stimulus was significantly larger in the HI group than in the LI group. These differences in N2 amplitude between conditions or groups were thought to be independent of other ERP components such as P300 and CNV. These results suggest that at least to some extent N2, which increased in amplitude when a greater effort was required to withhold the Go response, reflects the activity of a response inhibition system of the brain.     

Effects of the dopamine-related drug bromocriptine on event-related potentials and its relation to the law of initial value

Abstract Effects of the dopamine-related drug bromocriptine (BCT) on event-related potentials (ERP) were investigated in 18 healthy volunteers. Bromocriptine 2.5 mg or an inactive placebo was administered according to a completely randomized double-blind, cross-over design. The ERP were recorded 3 h after medication was given. Although BCT prolonged the P300 latency, it had no effect on the amplitudes of the ERP components as a whole. Bromocriptine increased the latencies of N100, P200 and P300 in the respective short-latency subject group, and decreased the latency of N200 in the long-latency subject group. It increased the amplitude of N200 in the low-amplitude subject group. It was concluded that the prolongation of P300 latency as a whole and the different responses that take place are dependent on the initial values and were recognized in the effect of a single administration of BCT 2.5 mg. The results of this study are discussed in relation to the law of initial value.     

Effects of the GABA Mimetic Drug, Sodium Valproate, on Event-Related Potentials and Its Relation to the Law of Initial Value

Abstract: The effects of γ-aminobutyric acid (GABA) mimetic drug sodium valproate (VPA) on event-related potentials (ERPs) were investigated in 18 healthy volunteers during an auditory odd ball task. VPA (200 or 400 mg) or an inactive placebo was administered according to a completely randomized double-blind, cross-over design. ERPs were recorded one hour after medication was given. VPA did not affect the latencies of N100, P200, N200 and P300. Although on the whole VPA had no effect on the amplitudes of the ERP components in the subjects, it increased the P300 amplitude in the low P300 amplitude subjects and decreased it in the high P300 amplitude subjects. This tendency toward a bidirectional response was also seen in the P200 and N200 amplitudes. It was concluded that the response which takes place being dependent on the difference in the initial values was recognized on the effect of a single administration of 200 or 400 mg VPA to ERPs. The results of this study are discussed, especially in relation to the law of initial value.     

Cat-P300 present after association cortex ablation

The cat-P300 is a positive endogenous potential, larger to a stimulus when rare than when frequent, with a latency of 200-500 msec. The role of polysensory association cortex, postulated to be important in human P300 generation, was assessed in the cat. EEG was recorded in 13 awake cats from a skull screw at the vertex. Stimuli included frequent (P = 0.80) 1 kHz and rare (P = 0.10) 2 kHz tone pulses with probabilities counterbalanced across 260-trial blocks. After 12 preoperative sessions, bilateral ablations were made of pericruciate cortex (4 cats), anterior lateral and medial suprasylvian gyri (4 cats) and all 3 areas (5 cats). Postoperatively, all 13 cats showed a P300 across 12 recording sessions. Thus polysensory association cortex is not essential for generation of the cat-P300.     

Effects of etizolam and ethyl loflazepate on the P300 event-related potential in healthy subjects

Background

Benzodiazepines carry the risk of inducing cognitive impairments, which may go unnoticed while profoundly disturbing social activity. Furthermore, these impairments are partly associated with the elimination half-life (EH) of the substance from the body. The object of the present study was to examine the effects of etizolam and ethyl loflazepate, with EHs of 6 h and 122 h, respectively, on information processing in healthy subjects.

Methods

Healthy people were administered etizolam and ethyl loflazepate acutely and subchronically (14 days). The auditory P300 event-related potential and the neuropsychological batteries described below were employed to assess the effects of drugs on cognition. The P300 event-related potential was recorded before and after drug treatments. The digit symbol test, trail making test, digit span test and verbal paired associates test were administered to examine mental slowing and memory functioning.

Results

Acute administration of drugs caused prolongation in P300 latency and reduction in P300 amplitude. Etizolam caused a statistically significant prolongation in P300 latency compared to ethyl loflazepate. Furthermore, subchronic administration of etizolam, but not ethyl loflazepate, still caused a weak prolongation in P300 latency. In contrast, neuropsychological tests showed no difference.

Conclusions

The results indicate that acute administration of ethyl loflazepate induces less effect on P300 latency than etizolam.     

State and trait markers of emotionally charged visual event-related potentials (P300) in drug-naïve schizophrenia

Aim: In the present study, we investigated the changes in P3 component in the emotionally charged visual event‐related potentials (ERP) in 30 drug‐naïve schizophrenic patients for up to 1 year. Methods: Visual oddball event‐related potential was recorded from six recording sites for crying baby or smiling baby photographs. ERP were recorded before the treatment (session 1 [S1]), after 3 months (session 2 [S2]), and after 12 months (session 3 [S3]), as well as in 30 healthy subjects. Results: Before taking medicine, there were no significant differences in the P300 amplitude between viewing photographs of a crying and a smiling baby. The P300 amplitude was significantly larger at S2 and S3 than at S1 for a crying baby, while there was no significant difference among sessions for a smiling baby after medication. A significant difference of the P300 amplitude was only observed between S3 and healthy subjects for a smiling baby. The P300 latency only when viewing a smiling face became significantly longer at S3 than those at S1 and S2. A significant negative correlation was obtained between the P300 amplitude changes upon viewing crying faces and negative syndrome score changes at the Pz site. Conclusion: The P300 amplitude induced by crying‐face stimuli may be a state marker and the P300 amplitude caused by smiling‐face stimuli may be a trait marker during recovery in schizophrenic patients. Atypical antipsychotic medications may be useful and may recover cognitive function reflected by the emotionally charged visual P300 components in schizophrenic patients.     

Clinical and neuropsychological correlates of the P300 in schizophrenia

We investigated the relationship between the P300, neuropsychological test performance and symptomatology in recent-onset schizophrenic patients (n = 45) to gain insight into underlying mechanisms of abnormal P300 in schizophrenia. The P300 was recorded in two sessions with an intermission of five minutes, at the midline frontal, central and parietal electrode site. P300 amplitude and latency were compared with those obtained in 25 controls. Twenty patients were treated with olanzapine and 19 patients with risperidone. P300 amplitude was smaller and latency longer in patients than in controls. In the patient group, parietal P300 amplitude reduction was related to poorer performance on neuropsychological tests of memory. Frontal P300 amplitude reduction was related to impaired selective attention. In patients with negative symptomatology, P300 amplitude was reduced in the second P300 session compared with the first. Patients on risperidone demonstrated a smaller parietal P300 amplitude than patients using olanzapine. Reduced parietal P300 amplitude could signify a dysfunction in the continuous memory updating of current events. Negative symptomatology may be associated with a time dependent decrease in neuronal firing, as indicated by reduced P300 amplitude in the second P300 session.     

Different brain mechanisms mediate sensitivity to sensory consonance and harmonic context: evidence from auditory event-related brain potentials

The goal of this study was to analyze the time-course of sensory (bottom-up) and cognitive (top-down) processes that govern musical harmonic expectancy. Eight-chord sequences were presented to 12 musicians and 12 nonmusicians. Expectations for the last chord were manipulated both at the sensory level (i.e., the last chord was sensory consonant or dissonant) and at the cognitive level (the harmonic function of the target was varied by manipulating the harmonic context built up by the first six chords of the sequence). Changes in the harmonic function of the target chord mainly modulate the amplitude of a positive component peaking around 300 msec (P3) after target onset, reflecting top-down influences on the perceptual stages of processing. In contrast, changes in the acoustic structure of the target chord (sensory consonance) mainly modulate the amplitude of a late positive component that develops between 300 and 800 msec after target onset. Most importantly, the effects of sensory consonance and harmonic context on the event-related brain potentials associated with the target chords were found to be independent, thus suggesting that two separate processors contribute to the building up of musical expectancy.     

Cat P300 present after primary auditory cortex ablation

A long-latency (200-500 msec) endogenous potential with characteristics of the human P300 was recorded over 12 sessions in 4 adult cats. Principal components analysis with t tests showed that this potential was significantly larger in response to rare auditory stimuli than to the same stimuli presented frequently. The primary auditory cortex was ablated bilaterally. The preoperative tone-elicited conditioned eye blink response remained postoperatively. After 12 postoperative sessions, statistical analyses of these data demonstrated that the P300-like potential was still present. Thus, the primary auditory cortex is not necessary for generation of the P300-like response in cats.     

Effects of caffeine on event-related potentials: Comparison of oddball with single-tone paradigms

We investigated the acute effects of caffeine (500 mg) on event-related potentials (ERP) in 10 healthy subjects using standard oddball and single-tone paradigms. Event-related potentials were recorded before oral ingestion of caffeine or placebo and 30 min and 210 min after. The oddball paradigm, but not the single-tone paradigm, showed that the P300 amplitude and the area were significantly increased 30 min after ingestion of caffeine and significantly decreased 30 min after ingestion of placebo. The effects of caffeine disappeared at 210 min. Neither the P300 latency nor the reaction time changed significantly with the oddball paradigm. However, the reaction time was shortened 30 min after ingestion of caffeine with the single-tone paradigm. These findings suggest that the caffeine-induced increase in the P300 amplitude may have resulted from the increased allocation of attentional resources to the discriminating process which was not, however, accompanied by facilitation of the process and that caffeine may specifically stimulate the discriminating process involved in the oddball paradigm. In addition, the simple psychomotor performance of button-pressing in response to a tone signal was accelerated by caffeine.     

N1--P2 component of the auditory evoked potential during alcohol intoxication and interaction of pyrithioxine in healthy adults.

The auditory evoked potential was used to assess the effect of alcohol intoxication (1 g/kg) and pyrithioxine (7 mg/kg) on 9 adult subjects. Its components in the latency range 50--250 msec (N1--P2) were studied for 6 g 30 min, during a constant level of alertness. Four periods were considered: alcohol alone, alcohol plus pyrithioxine, pyrithioxine plus alcohol and placebo. With alcohol alone the N1--P2 amplitude was small in the first part of the test and large in the second part as compared to placebo values. Pyrithioxine antagonism was greatest after alcohol had been resorbed. The placebo period indicated that amplitude changes were not due to long-term habituation, when the subject was kept alert.