Efficacy of Maternal Choline Supplementation During Pregnancy in Mitigating Adverse Effects of Prenatal Alcohol Exposure on Growth and Cognitive Function: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

BACKGROUND: We recently demonstrated the acceptability and feasibility of a randomized, double-blind choline supplementation intervention for heavy drinking women during pregnancy. In this study, we report our results relating to the efficacy of this intervention in mitigating adverse effects of prenatal alcohol exposure (PAE) on infant growth and cognitive function. METHODS: Sixty-nine Cape Coloured (mixed ancestry) heavy drinkers in Cape Town, South Africa, recruited in mid-pregnancy, were randomly assigned to receive a daily oral dose of either 2 g of choline or placebo from time of enrollment until delivery. Each dose consisted of an individually wrapped packet of powder that, when mixed with water, produced a sweet tasting grape-flavored drink. The primary outcome, eyeblink conditioning (EBC), was assessed at 6.5 months. Somatic growth was measured at birth, 6.5, and 12 months, recognition memory and processing speed on the Fagan Test of Infant Intelligence, at 6.5 and 12 months. RESULTS: Infants born to choline-treated mothers were more likely to meet criterion for conditioning on EBC than the placebo group. Moreover, within the choline arm, degree of maternal adherence to the supplementation protocol strongly predicted EBC performance. Both groups were small at birth, but choline-treated infants showed considerable catch-up growth in weight and head circumference at 6.5 and 12 months. At 12 months, the infants in the choline treatment arm had higher novelty preference scores, indicating better visual recognition memory. CONCLUSIONS: This exploratory study is the first to provide evidence that a high dose of choline administered early in pregnancy can mitigate adverse effects of heavy PAE on EBC, postnatal growth, and cognition in human infants. These findings are consistent with studies of alcohol-exposed animals that have demonstrated beneficial effects of choline supplementation on classical conditioning, learning, and memory.

Herbal Extracts That Reduce Ocular Oxidative Stress May Enhance Attentive Performance in Humans.

We used herbal extracts in this study to investigate the effects of blue-light-induced oxidative stress on subjects' attentive performance, which is also associated with work performance. We employed an attention network test (ANT) to measure the subjects' work performance indirectly and used herbal extracts to reduce ocular oxidative stress. Thirty-two subjects participated in either an experimental group (wearing glasses containing herbal extracts) or a control group (wearing glasses without herbal extracts). During the ANT experiment, we collected electroencephalography (EEG) and electrooculography (EOG) data and measured button responses. In addition, electrocardiogram (ECG) data were collected before and after the experiments. The EOG results showed that the experimental group exhibited a reduced number of eye blinks per second during the experiment and faster button responses with a smaller variation than did the control group; this group also showed relatively more sustained tension in their ECG results. In the EEG analysis, the experimental group had significantly greater cognitive processing, with larger P300 and parietal 2-6 Hz activity, an orienting effect with neural processing of frontal area, high beta activity in the occipital area, and an alpha and beta recovery process after the button response. We concluded that reducing blue-light-induced oxidative stress with herbal extracts may be associated with reducing the number of eye blinks and enhancing attentive performance.

Effects of anxiety sensitivity and expectations on the modulation of the startle eyeblink response during a caffeine challenge.

RATIONALE: The way in which the tendency to fear somatic arousal sensations (anxiety sensitivity), in interaction with the created expectations regarding arousal induction, might affect defensive responding to a symptom provocation challenge is not yet understood. OBJECTIVES: The present study investigated the effect of anxiety sensitivity on autonomic arousal, startle eyeblink responses, and reported arousal and alertness to expected vs. unexpected caffeine consumption. METHODS: To create a match/mismatch of expected and experienced arousal, high and low anxiety sensitive participants received caffeine vs. no drug either mixed in coffee (expectation of arousal induction) or in bitter lemon soda (no expectation of arousal induction) on four separate occasions. Autonomic arousal (heart rate, skin conductance level), respiration (end-tidal CO2, minute ventilation), defensive reflex responses (startle eyeblink), and reported arousal and alertness were recorded prior to, immediately and 30 min after beverage ingestion. RESULTS: Caffeine increased ventilation, autonomic arousal, and startle response magnitudes. Both groups showed comparable levels of autonomic and respiratory responses. The startle eyeblink responses were decreased when caffeine-induced arousal occurred unexpectedly, e.g., after administering caffeine in bitter lemon. This effect was more accentuated in high anxiety sensitive persons. Moreover, in high anxiety sensitive persons, the expectation of arousal (coffee consumption) led to higher subjective alertness when administering caffeine and increased arousal even if no drug was consumed. CONCLUSIONS: Unexpected symptom provocation leads to increased attention allocation toward feared arousal sensations in high anxiety sensitive persons. This finding broadens our understanding of modulatory mechanisms in defensive responding to bodily symptoms.

Evidence for TRPA1 involvement in central neural mechanisms in a rat model of dry eye.

Dry eye (DE) disease is commonly associated with ocular surface inflammation, an unstable tear film and symptoms of irritation. However, little is known about the role of central neural mechanisms in DE. This study used a model for persistent aqueous tear deficiency, exorbital gland removal, to assess the effects of mustard oil (MO), a transient receptor potential ankyrin (TRPA1) agonist, on eyeblink and eyewipe behavior and Fos-like immunoreactivity (Fos-LI) in the trigeminal brainstem of male rats. Spontaneous tear secretion was reduced by about 50% and spontaneous eyeblinks were increased more than 100% in DE rats compared to sham rats. MO (0.02-0.2%) caused dose-related increases in eyeblink and forelimb eyewipe behavior in DE and sham rats. Exorbital gland removal alone was sufficient to increase Fos-LI at the ventrolateral pole of trigeminal interpolaris/caudalis (Vi/Vc) transition region, but not at more caudal regions of the trigeminal brainstem. Under barbiturate anesthesia ocular surface application of MO (2-20%) produced Fos-LI in the Vi/Vc transition, in the mid-portions of Vc and in the trigeminal caudalis/upper cervical spinal cord (Vc/C1) region that was significantly greater in DE rats than in sham controls. MO caused an increase in Fos-LI ipsilaterally in superficial laminae at the mid-Vc and Vc/C1 regions in a dose-dependent manner. Smaller, but significant, increases in Fos-LI also were seen in the contralateral Vc/C1 region in DE rats. TRPA1 protein levels in trigeminal ganglia from DE rats ipsilateral and contralateral to gland removal were similar. Persistent tear reduction enhanced the behavioral and trigeminal brainstem neural responses to ocular surface stimulation by MO. These results suggested that TRPA1 mechanisms play a significant role in the sensitization of ocular-responsive trigeminal brainstem neurons in this model for tear deficient DE.

Clonidine normalizes sensorimotor gating deficits in patients with schizophrenia on stable medication.

BACKGROUND: Cognitive deficits form core features in schizophrenia. Several studies have shown improvements in prefrontal cognitive function by α 2 -agonists in schizophrenia. In the present study, it was investigated whether clonidine (an α 2 -adrenoceptor agonist) could normalize sensorimotor gating deficits in schizophrenia. METHODS: In a double blind, placebo controlled, randomized, yet balanced, cross-over experiment, 20 male schizophrenia patients on stable medication were assessed in an auditory prepulse inhibition (PPI), sensitization, and habituation of the startle reflex paradigm on 5 occasions: once after oral administration of placebo and after a single dose of 25, 50, 75, and 150 µg of clonidine. Their results were compared with 20 age- and gender-matched healthy volunteers, who received no treatment. RESULTS: In the placebo treatment, patients showed deficient PPI and sensitization, yet normal habituation compared with the controls. Except the highest dose, all dosages of clonidine significantly increased percentage PPI in the patients compared with placebo, to such levels that it no longer differed significantly from the healthy controls. However, none of the dosages increased sensitization or influenced habituation. CONCLUSIONS: This is the first study to show that even a single low dose of clonidine added to the medical treatment of patients with schizophrenia who are clinically stable on their antipsychotic medication not only significantly ameliorates their PPI deficits, but also normalizes them. The results have a potentially high clinical relevance for the medical treatment of schizophrenia.

Effect of spinal cord injury and of intrathecal baclofen on brainstem reflexes.

Reorganization of neural circuits within the central nervous system following injury appears to be a means of compensatory mechanism for loss of function. Reorganization following spinal cord injury is known to evoke changes at the cortical and spinal cord levels. Recent studies, however, provide evidence of enhanced brainstem reflexes and alterations in excitatory and inhibitory interneuronal brainstem circuits, suggesting that reorganization following spinal cord injury occurs also at the brainstem level. Reversal of these changes by continuous intrathecal baclofen infusion to normal levels or beyond indicates strong GABAergic involvement. Rapid changes in the blink reflex and its prepulse inhibition following intrathecal baclofen bolus application that parallel clinical changes in muscle hypertonia suggest a muscle tone regulating effect of baclofen at the brainstem level. Enhanced brainstem reflexes in spinal cord injury patients may be the consequence of decreased GABA-mediated inhibition and/or strengthening of facilitatory connections due to either direct or indirect plastic changes occurring at the brainstem level. Modulation of brainstem reflexes by baclofen may foster the understanding of pathophysiological mechanisms underlying diseases with increased brainstem activity. Rehabilitation after central nervous system injury will always be a challenge, but understanding the mechanisms of reorganization of undamaged neural pathways may help to develop better strategies for enhancing neuronal plasticity and for implementing neuronal reorganization into carefully planned therapy.

Acoustic startle reduction in cocaine dependence persists for 1 year of abstinence.

RATIONALE: Chronic cocaine use results in long-lasting neurochemical changes that persist beyond the acute withdrawal period. Previous work from our group reported a profound reduction in the acoustic startle response (ASR) in chronic cocaine-dependent subjects in early abstinence compared to healthy controls that may be related to long-lasting neuroadaptations following withdrawal from chronic cocaine use. OBJECTIVES: This study aims to investigate the persistence and time course of the decrements in the ASR of cocaine-dependent subjects during prolonged abstinence. METHODS: Seventy-six cocaine-dependent (COC) subjects and 30 controls (CONT) were tested, the former after a period of heavy cocaine dependence. COC subjects were retested sequentially for 1 year of abstinence or until relapse. ASR testing was conducted at 3-dB levels and the eye-blink component of the startle response was quantified with electromyographic recording of the orbicularis oculi muscle. RESULTS: While there was no difference in startle magnitude between CONT and COC in early abstinence, by day 40 of abstinence COC subjects exhibited a statistically significant decline (p = 0.0057) in ASR magnitude as compared with CONT and this decrement persisted for up to 1 year of abstinence (p = 0.0165). In addition, startle latency was slower in COC subjects as compared with CONT at all stages of abstinence. CONCLUSIONS: These results replicate and expand upon the earlier finding that chronic cocaine use impairs the ASR in a manner that persists beyond the acute withdrawal period. This phenomenon may represent a biological measure of long-term neural changes accompanying cocaine dependence and subsequent withdrawal.

Effect of aripiprazole, risperidone, and olanzapine on the acoustic startle response in Japanese chronic schizophrenia.

BACKGROUND: Studies have also shown that differences in the kind of the antipsychotics influenced disruption of the sensorimotor gating system, including prepulse inhibition (PPI), acoustic startle reflex (ASR), and habituation (HAB). We investigated the influence on startle response in chronic schizophrenia in 20 patients with schizophrenia taking risperidone, 21 patients with schizophrenia taking olanzapine, and 20 patients with schizophrenia taking aripiprazole. METHOD: The patients who participated in this study were on maintenance therapy with only one antipsychotic drug for 4 months. We performed the test for the association between all PPI measures (ASR, HAB, and PPI at prepulse sound pressure intensities of 82, 86, and 90 dB) and each the risperidene, olanzapine, and aripiprazole groups, with analysis of covariance (ANCOVA; using age, duration of illness, and daily dose of the antipsychotic as covariates). Also, when significant difference was detected in ANCOVA, the differences of PPI measures between every pairs of two drug groups were tested as a post hoc analysis with the use of t test and Bonferroni's correction of multiple tests. RESULT: We found that PPI90 showed significant differences with ANCOVA among patients with schizophrenia taking each of the antipsychotics. When we performed a post hoc analysis for PPI90, the value was higher in the aripiprazole group than in the olanzapine group and higher in the risperidone group than in the olanzapine group. CONCLUSION: Aripiprazole and risperidone may improve PPI90. ASR, HAB, PPI82, and PPI86 were no different among the Japanese schizophrenic patient groups with different antipsychotics.

Electrical activation of the orbicularis oculi muscle does not increase the effectiveness of botulinum toxin type A in patients with blepharospasm.

BACKGROUND: Our primary aim in this study was to determine whether electrically induced activation of the injected muscle increases effectiveness of botulinum type A toxin (BonT-A) in patients with blepharospasm (BPS). The second aim was to assess the safety of BonT-A by investigating whether BonT-A injection alters the excitability of blink reflex circuits in the brainstem. METHODS: Twenty-three patients with BPS received BonT-A (Botox) injected bilaterally into the orbicularis oculi muscle at a standard dose. In 18 patients, electrically induced muscle activation of the orbicularis oculi muscle on one side was performed for 60 min (4 Hz frequency) in a single session, immediately after BonT-A injection and in five patients for 60 min once a day for five consecutive days. The severity of BPS was assessed clinically with the BPS score. Compound muscle action potential (cMAPs) from the orbicularis oculi muscles were measured bilaterally. The blink reflex recovery cycle was studied at interstimulus intervals of 250 and 500 ms. Participants underwent clinical and neurophysiological assessment before BonT-A injection (T0) and 2 weeks thereafter (T1). RESULTS: Compound muscle action potential amplitude significantly decreased at T1 but did not differ between stimulated and non-stimulated orbicularis oculi in the two groups. BonT-A injection left the blink reflex recovery cycle tested on the stimulated and non-stimulated sides unchanged. CONCLUSIONS: In patients with BPS, the electrically induced muscle activation neither increases the effectiveness of BonT-A nor produces larger electrophysiological peripheral effects. The lack of BonT-A-induced changes in the blink reflex recovery cycle provides evidence that BonT-A therapy is safe in patients with BPS.

Cerebellar inactivation impairs cross modal savings of eyeblink conditioning.

Eyeblink conditioning using a conditioned stimulus (CS) from one sensory modality (e.g., an auditory CS) is greatly enhanced when the subject is previously trained with a CS from a different sensory modality (e.g., a visual CS). The enhanced acquisition to the second modality CS results from cross modal savings. The current study was designed to examine the role of the cerebellum in establishing cross modal savings in eyeblink conditioning with rats. In the first experiment rats were given paired or unpaired presentations with a CS (tone or light) and an unconditioned stimulus. All rats were then given paired training with a different modality CS. Only rats given paired training showed cross modal savings to the second modality CS. Experiment 2 showed that cerebellar inactivation during initial acquisition to the first modality CS completely prevented savings when training was switched to the second modality CS. Experiment 3 showed that cerebellar inactivation during initial cross modal training also prevented savings to the second modality stimulus. These results indicate that the cerebellum plays an essential role in establishing cross modal savings of eyeblink conditioning.

Eyeblink conditioning anomalies in bipolar disorder suggest cerebellar dysfunction.

OBJECTIVES: Accumulating research implicates the cerebellum in non-motor psychological processes and psychiatric diseases, including bipolar disorder (BD). Despite recent evidence that cerebellar lesions have been documented to trigger bipolar-like symptoms, few studies have directly examined the functional integrity of the cerebellum in those afflicted with BD. METHODS: Using a single-cue delay eyeblink conditioning procedure, the functional integrity of the cerebellum was examined in 28 individuals with BD (9 manic, 8 mixed, and 11 euthymic) and 28 age-matched healthy controls. RESULTS: Analysis of the bipolar group as a whole indicated a conditioned response acquisition and timing deficit compared to controls. However, when the bipolar group was categorized according to mood state (mixed, manic, euthymic), individuals tested during mixed episodes were strikingly impaired, performing significantly worse than all other groups on both the acquisition and timing of conditioned responses. CONCLUSIONS: These findings extend prior research implicating cerebellar functional abnormalities in BD and suggest that cerebellar dysfunction may be associated with mood state and course of illness.

Attenuation of auditory startle and prepulse inhibition by unexpected changes in ambient illumination through dopaminergic mechanisms.

We investigated the role of dopaminergic mechanisms in the attenuation of the acoustic startle response and prepulse inhibition (PPI) in rats by the introduction of unexpected changes in environment illumination. Experiment 1 showed that Dark-to-Light transitions robustly reduce startle responses and PPI. Experiment 2 showed that this phenomenon habituates across repeated testing sessions and reappears after an interval without testing. Experiment 3 demonstrated that haloperidol blocks the startle and PPI-reducing effect of the Dark-to-Light transition. We show how a computational model of acoustic startle response and prepulse inhibition can be extended to incorporate the empirical effects demonstrated in this study. We conclude that sensory gating as measured by prepulse inhibition is markedly attenuated in situations where novel stimuli are introduced during a test session and that dopaminergic systems may be involved in the dynamic changes evoked by the onset of illumination.

Ontogenetic change in the auditory conditioned stimulus pathway for eyeblink conditioning.

Two experiments examined the neural mechanisms underlying the ontogenetic emergence of auditory eyeblink conditioning. Previous studies found that the medial auditory thalamus is necessary for eyeblink conditioning with an auditory conditioned stimulus (CS) in adult rats. In experiment 1, stimulation of the medial auditory thalamus was used as a CS in rat pups trained on postnatal days (P) 17-18, 24-25, or 31-32. All three age groups showed significant acquisition relative to unpaired controls. However, there was an age-related increase in the rate of conditioning. Experiment 2 examined the effect of inactivating the medial auditory thalamus with muscimol on auditory eyeblink conditioning in rats trained on P17-18, 24-25, or 31-32. Rat pups trained on P24-25 and P31-32, but not P17-18, showed a significant reduction in conditioned responses following muscimol infusions. The findings suggest that the thalamic contribution to auditory eyeblink conditioning continues to develop through the first postnatal month.

Facilitated acquisition of the classically conditioned eyeblink response in women taking oral contraceptives.

Although anecdotal reports suggest that associative learning processes are affected by menstrual phase, empirical evidence has been equivocal. Moreover, there is a dearth of research concerning fluctuations of artificial or exogenous female hormones on learning and memory. Therefore, in this preliminary study we assessed learning in women who take oral contraceptives and those who do not during the three phases of the menstrual cycle: early, middle, and later cycle. The behavioral assessment included short-trace eyeblink conditioning, acoustic startle reactivity, and a fine motor coordination task (grooved pegboard). Oral contraceptive users generally acquired the conditioned eyeblink response better than non-users. Similar enhancements were observed for fine motor coordination and startle responsiveness. Further research will need to distinguish whether the hormone influence is upon the associative processes or the sensory-motor pathways involved in nonassociative learning.

Impaired prepulse inhibition and habituation of acoustic startle response in Japanese patients with schizophrenia.

Prepulse inhibition (PPI) and habituation of the acoustic startle reflex (ASR) are considered to be candidate endophenotypes of schizophrenia. However, to our knowledge, only one group has investigated these startle measures in Asian patients with schizophrenia. In the present study, we evaluated these startle measures in 51 Japanese patients with schizophrenia and compared them with those of 55 healthy age- and sex-matched Japanese controls. A human startle response monitoring system was used to deliver acoustic startle stimuli, and record and score the electromyographic activity of the orbicularis oculi muscle. The startle measures examined were mean magnitude of ASR to pulse alone trials in initial block (SR), habituation of ASR during the session (HAB), and PPI at prepulse intensities of 82 dB (PPI82), 86 dB (PPI86), and 90 dB (PPI90) sound pressure level. SR was not significantly different between the patients and controls. Patients displayed significantly reduced HAB and PPI for all prepulse intensities compared to controls. The greatest statistical difference in PPI between patients and controls was found with PPI86. This did not correlate with any clinical variable in each group. Our results indicate that PPI and habituation of ASR are impaired in Asian patients with schizophrenia.

Medial auditory thalamus inactivation prevents acquisition and retention of eyeblink conditioning.

The auditory conditioned stimulus (CS) pathway that is necessary for delay eyeblink conditioning was investigated using reversible inactivation of the medial auditory thalamic nuclei (MATN) consisting of the medial division of the medial geniculate (MGm), suprageniculate (SG), and posterior intralaminar nucleus (PIN). Rats were given saline or muscimol infusions into the MATN contralateral to the trained eye before each of four conditioning sessions with an auditory CS. Rats were then given four additional sessions without infusions to assess savings from the initial training. All rats were then given a retention test with a muscimol infusion followed by a recovery session. Muscimol infusions through cannula placements within 0.5 mm of the MGm prevented acquisition of eyeblink conditioned responses (CRs) and also blocked CR retention. Cannula placements more than 0.5 mm from the MATN did not completely block CR acquisition and had a partial effect on CR retention. The primary and secondary effects of MATN inactivation were examined with 2-deoxy-glucose (2-DG) autoradiography. Differences in 2-DG uptake in the auditory thalamus were consistent with the cannula placements and behavioral results. Differences in 2-DG uptake were found between groups in the ipsilateral auditory cortex, basilar pontine nuclei, and inferior colliculus. Results from this experiment indicate that the MATN contralateral to the trained eye and its projection to the pontine nuclei are necessary for acquisition and retention of eyeblink CRs to an auditory CS.

Patients with adverse mood effects from combined oral contraceptives have lower levels of prepulse inhibition than healthy controls.

BACKGROUND: Negative mood symptoms remain one of the major reasons for discontinuation of oral contraceptive pills. The aim of this study was to compare acoustic startle response and prepulse inhibition (PPI) in women with different experience of oral contraceptive pills. METHODS: Thirty women currently on combined oral contraceptives (COCs) with no reports of adverse mood symptoms, 28 women currently on COCs and experiencing mood-related side effects from treatment, 27 women who had discontinued COC use for reasons other than adverse mood symptoms and 32 women who had discontinued COC use due to adverse mood effects were included. The eyeblink component of the acoustic startle reflex was assessed using electromyographic measurements of musculus Orbicularis Oculi. Twenty pulse-alone trials (115dB 40ms broad-band white noise) and 40 prepulse-pulse trials were presented. The prepulse stimuli consisted of a 115dB 40ms noise burst preceded at a 100ms interval by 20ms prepulses that were 72, 74, 78, or 86dB. RESULTS: Patients with adverse mood effects of COCs exhibited lower levels of PPI with 86dB prepulse compared to COC users with no adverse effects of COCs (p<0.05). There was no difference in PPI between the two groups of prior COC users. No significant difference was found between the groups regarding acoustic startle response. CONCLUSION: Relative to COC users with no reports of adverse mood symptoms, subjects suffering from COC-induced negative mood displayed deficits in PPI of acoustic startle. The fact that there was no difference in PPI between the two groups of prior COC users indicates that deficient PPI is related to adverse mood effects caused by COCs.

The indirect serotonergic agonist d-fenfluramine and prepulse inhibition in healthy men.

The specific serotonin (5-HT) releaser, d-fenfluramine (DFEN) was used as a probe of serotonergic effects on prepulse inhibition (PPI). We wished to explore the notion that increased central serotonergic transmission was in part responsible for the psychotomimetic effects of hallucinogens using a relevant and objective physiological measure. Disruption of PPI is considered a valid pharmacological model of some aspects of the behavioural abnormalities in schizophrenia. The aim of this study was to test the hypothesis that increasing central 5-HT neurotransmission with DFEN would produce disruption of PPI. Eighteen healthy male subjects received 45mg of DFEN or placebo in a random order, within-subject, double-blind, and cross-over design. Prepulse to pulse intervals were 30ms and 120ms. The Brief Psychiatric Rating Scale (BPRS) was administered. Although mean PPI at the two prepulse intervals was not significantly different, DFEN prevented the increase in PPI usually seen at the 120ms interval and significantly increased startle magnitude, but did not alter habituation. There were no significant associations between PPI effects and behaviour.

A fMRI investigation of startle gating deficits in schizophrenia patients treated with typical or atypical antipsychotics.

A key feature of schizophrenia is the inability to screen out irrelevant sensory input. Prepulse inhibition (PPI) of the startle response, a cross-species measure of sensorimotor gating, provides a valuable opportunity to study this feature. PPI is reliably impaired in schizophrenia. Animal models of disrupted PPI have proved valuable for the evaluation of antipsychotic substances. The cortico-striato-pallido-thalamic circuitry is primarily responsible for modulation of PPI in animals. We examined PPI and its brain correlates, using functional magnetic resonance imaging (fMRI), in men with schizophrenia treated with typical or atypical antipsychotics. Thirty men with schizophrenia on stable doses of typical antipsychotics (n=10), risperidone (n=10) or olanzapine (n=10; 9 with usable fMRI data) and 12 healthy men underwent psychophysiological testing and fMRI during a tactile PPI paradigm. The results showed reduced PPI of the eye-blink startle response in patients compared with healthy controls. Within the patient group, those on typical antipsychotics showed significantly impaired PPI but risperidone- or olanzapine-treated patients showed a milder (non-significant) deficit. Increased activity in the striatum, thalamus, insula, hippocampal, temporal, inferior frontal and inferior parietal regions occurred in association with PPI in controls. Patients treated with risperidone or olanzapine, but not with typical antipsychotics, showed significant activation in PPI-relevant regions. Our findings provide preliminary evidence that atypical antipsychotics positively influence PPI and partially restore associated brain functions in schizophrenia. Imaging data buttress the validity of PPI as a useful animal model of schizophrenia.

[Pharmacodynamics of two different propofol formulations]. / Pharmakodynamik zweier unterschiedlicher Propofolformulierungen.

BACKGROUND: Propofol is nowadays available in various lipid formulations. We compared two different propofol formulations with respect to pharmacodynamics, using the EEG and clinical signs. MATERIALS AND METHODS: Ten volunteers received Diprivan 1% and Propofol 1% MCT Fresenius as a computer controlled infusion with increasing propofol target concentrations. A sigmoid E(max) model with effect compartment was estimated for the median frequency of the EEG power spectrum, based on measured arterial propofol plasma concentrations. Clinical pharmacodynamics were assessed by reaction on acoustic stimuli, eyelid reflex and corneal reflex. RESULTS: The drugs did not differ in pharmacodynamics with respect to EEG (EC(50) 2.1+/-0.6 for Diprivan and 2.1+/-0.5 microg/ml for Propofol Fresenius) and clinical signs. The pharmacodynamic model was characterized by a steep concentration effect relationship and a distinct hysteresis between propofol plasma concentration and effect (k(e0) 0.12+/-0.04 and 0.12+/-0.5 min(-1)). CONCLUSIONS: The investigated lipid formulations have no influence on the pharmacodynamics of propofol.