Single Dose Effects of Pascoflair^(█) on Current Source Density(CSD)of Human EEG

Pascoflair? 425 mg is a herbal drug based on Passiflora incarnata dry extract and is registered in different countries for the treatment of nervous restlessness and anxiety and also as an aid to sleep. The study was initiated for the quantitative assessment of the effect of this preparation on brain electric activity and cognition in human volunteers. Quantitative electroencephalographic current source density (CSD) from 16 healthy male and female human volunteers (average age 49 years) was used in a randomized, placebo-controlled crossover study. Data were taken 0.5, 1.5, 3 and 4 hours after administration of the preparations under the conditions of 6 minutes eyes open, 5 minutes d2 concentration test, mathematical calculation test and memory test respectively. During mental load, changes in spectral band power were used to analyse drug-induced effects. All variables were fed into a linear discriminant analysis (LDA) for comparison with other drug profiles. Spectral power in the delta and theta range was significantly attenuated at 3 and 4 hours after administration in comparison with the time-dependent increase normally observed due to circadian rhythm. Discriminant analysis revealed a difference to placebo for all recordings as early as 30 minutes after intake of 3 coated tablets of Pascoflair? 425 mg. Using LDA data location within the poly-dimensional space, verum was projected into the area of the effects of Gingko/Ginseng as reference drugs tested earlier under identical conditions. Psychometric performance was not disrupted. Pascoflair? 425 mg can be regarded as a well characterized plant-derived drug with anxiolytic and calming properties without negative sedative and cognition-attenuating side effects. Current results document the effecttiveness of the preparation as early as after 30 minutes. In addition, they indicate persistence of good mental performance for hours. Trial registration: the study has been registered at ClinicalTrials.gov under NCT01047605.

Intracellular and current source density analysis of pretectal input to the optic tectum of the frog

Objective Electrophysiological examination of the ipsilateral pretectotectal projection has proved that pretectal cells elicit strong suppressive responses to the ipsilateral tectum.However,the neural mechanisms underlying the contralateral pretectotectal prejection are still obscure.The present study aimed to examine the synaptic nature of pretectal nuclei and contralateral tectal cells,and to demonstrate the spatiotemporal pattern of neuronal activity in the 2 main brain structures. Methods Intracellular recording and current source density（CSD）analysis were used to test the complexity of neuronal mechanism of pretectotectal information transfer.Results The pretectal stimulation elicited only one type of response on the contralateral tectum,the inhibitory postsynaptic potential（IPSP）.The majority of contra-induced IPSPs were assumed to be polysynaptically driven.In the CSD analysis,only one sink with short latency was observed in each profile.The ipsilateral projection produced a prominent monosynaptic sink in layer 8 of tectum.Recipient neurons were located in layers 6 and 7 of tectum.The result confirmed former findings from ipsilateral intracellular recordings.Conclusion These results suggest the following neuronal circuit：afferents from the pretectal nuclei broadly inhibit both tectal neuron,and since no second sink occurs in tectal layers,the pretectotectal excitatory afferents probably do not extend over the whole tectum,but are within limited state.The results of intracellular recording and CSD analysis further provide evidence of how pretectal afferent activity flows within the tectal laminae.

Psychophysiological Effects of Sideritis and Bacopa Extract and Three Combinations Thereof—A Quantitative EEG Study in Subjects Suffering from Mild Cognitive Impairment (MCI)

Mild cognitive impairment (MCI) is regarded as a transitional stage during the development of Alzheimer’s disease. Diagnosis of MCI can be obtained by the questionnaire “DemTect” in German speaking countries. Quantitative assessment has been successfully performed using psychometric testing concomitantly with quantitative EEG recording. The present investigation aimed at the possible treatment of MCI with two botanicals, namely extracts from Sideritis scardica (500 mg) or Bacopa monnieri (320 mg) and three combinations thereof using this method in order to find a new treatment. The performance of the d2-test, an arithmetic calculation test (CPT) and a memory-test revealed better performance for the d2-test only in the presence of Sideritis extract or the combinations with Bacopa extract. Quantitative EEG assessment during the different experimental conditions showed massive differences between both extracts. Whereas Sideritis extract and its combination with a low amount of Bacopa extract (160 mg) induced increases of spectral power in fronto-temporal brain areas, Bacopa and the combination of Sideritis with high amounts of Bacopa extract produced attenuation of all waves except for delta in fronto-temporal brain areas. These differences were also documented by quantitative EEG maps in comparison to Placebo. A different action of both extracts was confirmed by discriminant analysis, where Sideritis extract and its combination with low Bacopa grouped together quite at distance to Bacopa and the combination of Sideritis with high Bacopa. A combination of Sideritis extract with a low amount of Bacopa should be tested with daily repetitive dosing for at least 4 weeks as a consequence.

Psychophysiological Effects of a Combination of Sideritis and Bacopa Extract (memoLoges®) in 32 Subjects Suffering from Mild Cognitive Impairment. A Double-Blind, Randomized, Placebo-Controlled, 2-Armed Study with Parallel Design

Mild cognitive impairment (MCI) can be regarded as a non-demented transitional stage during the development of Alzheimer’s disease. Early recognition of this stage might increase the chance of prevention by early treatment. Within a pilot study, two plant-derived preparations and mixtures thereof were tested successfully in subjects suffering from MCI. A combination of Sideritis scardica and Bacopa monnieri extract (memoLoges®) was chosen now for a repetitive dosing during 4 weeks. Thirty-two subjects aged 50 to 80 years and suffering from MCI (having a DemTect questionnaire score between 8 and 13) were recruited for intake of 2 capsules of the preparation per day. Quantitative EEG recording during relaxation and concomitant performance of three 5 minutes lasting psychometric tests (d2-concentration test, arithmetic calculation test and memory test) was achieved at the first day and one day after the last repetitive intake. Seventeen channels of EEG and one channel EOG (for artefact rejection) were recorded. After frequency analysis (FFT) current source density was calculated as reported earlier. One, two and three hours after intake of the herbal extract or placebo the whole procedure was repeated. Brain imaging was achieved by conversion of numerical values of spectral EEG power into spectral colors and additive color mixture according to RGB as used in TV settings. Intake of memoLoges® induced a trend of improvement of performance in psychometric testing (all three tests). During relaxation quantitative assessment of EEG data revealed attenuation of delta and theta spectral power in frontal brain as likewise reported in the presence of the Alzheimer drug rivastigmine, bringing the spectrum back to “normality”. During mental work memoLoges® induced statistically significant increases of beta power. Since MCI subjects produce less beta power in comparison to healthy subjects, this increase must likewise be seen as a positive effect pointing to a healthier spectrum.

Proof of Effectiveness of PASCOFLAIR®in Subjects Suffering from Examination Anxiety Using Quantitative EEG in Combination with Eye-Tracking (EnkephaloVision). A Double-Blind, Randomized, Placebo Controlled, 2-Armed, Phase IV Study in Parallel Design

The pharmaco-dynamic action of plant-derived drugs still remains a big challenge in the field of pharmacology. This applies especially for the discovering of the possible mechanism of action. With respect to the brain, surrogate parameters may be very helpful. Non-invasive pharmaco-EEG has been proven to provide valid information on drug effects in general. Fast dynamic EEG recording with epoch length of 364 ms has now been achieved in combination with Eye-Tracking in order to elucidate single scenes during cognitive and emotional challenges (EnkephaloVision). The present investigation deals with the psychophysiological characterization of the effect of a plant-derived preparation marketed in Germany under the name of PASCOFLAIR® containing 425 mg of passionflower extract in subjects suffering from examination anxiety. Forty healthy volunteer subjects (17 men and 23 woman), with ages varying between 18 and 40 years (26 ± 6.726 for men and 25 ± 5.397 for women) were included into the study when having a score higher than 60 in the PAF (Pr&#220fungsangstfragebogen). Spectral power analysis of pre-drug data with respect to beta waves revealed a significant correlation to the score of the PAF. Increases of delta, theta and beta waves as induced by 4 cognitive and 4 emotional challenges were attenuated in the presence of 2 tablets of PASCOFLAIR® already 45 minutes after intake in a statistically significant manner in comparison to placebo. Regarding attenuation of beta1 and beta2 spectral power, effects on glutamatergic and GABAergic neurotransmission, respectively, can be suspected according to our knowledge of frequency—transmitter relations. Accordingly, this attenuation must be interpreted as ability to counteract examination induced stress symptoms. Results confirm and extend earlier experimental data showing a calming action of PASCOFLAIR®.

AB050.Neuronal response to visual contrast varies as function of the cortical layer

Background:For years,studies using several animal models have highlighted the predominant role of the primary visual area in visual information processing.Its six cortical layers have morphological,hodological and physiological differences,although their roles regarding the integration of visual contrast and the messages sent by the layers to other brain regions have been poorly explored.Given that cortical layers have distinct properties,this study aims to understand these differences and how they are affected by a changing visual contrast.Methods:A linear multi-channel electrode was placed in the primary visual cortex(V1)of the anesthetized mouse to record neuronal activity across the different cortical layers.The laminar position of the electrode was verified in real time by measuring the current source density(CSD)and the multi-unit activity(MUA),and confirmed post-mortem by histological analysis.Drifting gratings varying in contrast enabled the measurement of the firing rate of neurons throughout layers.We fitted this data to the Naka-Rushton equations,which generated the contrast response function(CRF)of neurons.Results:The analysis revealed that the baseline activity as well as the rate of change of neural discharges(the slope of the CRF)had a positive correlation across the cortical layers.In addition,we found a trend between the cortical position and the contrast evoking the semi-saturation of the activity.A significant difference in the maximum discharge rate was also found between layers II/III and IV,as well as between layers II/III and V.Conclusions:Since layers II/III and V process visual contrast differently,our results suggest that higher cortical visual areas,as well subcortical regions,receive different information regarding a change in visual contrast.Thus,a contrast may be processed differently throughout the different areas of the visual cortex.

Psychophysiological Effectiveness of Calmvalera Hevert Tablets as Measured by EnkephaloVision in Anxious Subjects during Audio-Visual Cognitive and Emotional Challenges: A Double-Blind, Randomized, Placebo-Controlled, 2-Armed, Phase IV Study in Parallel Design

Subjects suffering from anxiety during examinations often take drugs with considerable side effects. As alternative, homeopathic preparations virtually lack side effects in general. However, clinical efficacy has to be demonstrated. This experimental series was initiated to provide evidence, that Calmvalera Hevert tablets, marketed for treatment of nervous restlessness and better coping with stress, have an influence on brain electric activity. In order to test this, a new clinical design was used: “EnkephaloVision”. It consists of the combination of quantitative EEG recording with time epochs of 364 ms (Neurocode-Tracking) with conventional Eye-Tracking. Seventeen channels of EEG and one channel EOG were recorded. After frequency analysis (FFT) current source density was calculated. Recording was performed in the presence of a video clip, which contained several different cognitive and emotional challenges in series. Twenty-four male and female subjects having a score >60 in an anxiety questionnaire (Prüfungsangstfragebogen PAF-S) were recruited to participate. A correlation between the Hamilton anxiety score and spectral alpha1 power during the recording condition “eyes open” before drug intake was detected. Spectral power was averaged including Cz, F3 and F4 electrode positions. Audiovisual challenges induced spectral changes with respect to delta, theta and beta power, not in the alpha ranges, to a different but statistically significant degree. Intake of Calmvalera Hevert tablets resulted in statistically significant increases of alpha1 and alpha2 spectral power during most of the recording conditions within the left hemisphere. Increases of alpha activity have been related to relaxation and calmness as reported in the literature. Discriminant analysis of the whole data set revealed a clear difference between verum and placebo and a projection of the data into the vicinity of other plant-derived calming preparations. Performance of psychometric tasks was not disturbed. Efficacy of Calmvalera Hevert tablets points to active molecules contained due to low triturations (D2 - D8).

Neural circuits and temporal plasticity in hindlimb representation of rat primary somatosensory cortex:revisited by multi-electrode array on brain slices

Objective The well-established planar multi-electrode array recording technique was used to investigate neural circuits and temporal plasticity in the hindlimb representation of the rat primary somatosensory cortex （S1 area） . Methods Freshly dissociated acute brain slices of rats were subject to constant perfusion with oxygenated artificial cerebrospinal fluid （95% O2 and 5% CO2） , and were mounted on a Med64 probe （64 electrodes, 8×8 array） for simultaneous multi-site electrophysiological recordings. Current sources and sinks across all the 64 electrodes were transformed into two-dimensional current source density images by bilinear interpolation at each point of the 64 electrodes. Results The local intracortical connection, which is involved in mediation of downward information flow across layers II-VI, was identified by electrical stimulation （ES） at layers II-III. The thalamocortical connection, which is mainly involved in mediation of upward information flow across layers II-IV, was also characterized by ES at layer IV. The thalamocortical afferent projections were likely to make more synaptic contacts with S1 neurons than the intracortical connections did. Moreover, the S1 area was shown to be more easily activated and more intensively innervated by the thalamocortical afferent projections than by the intracortical connections. Finally, bursting conditioning stimulus （CS） applied within layer IV of the S1 area could success-fully induce long-term potentiation （LTP） in 5 of the 6 slices （83.3%） , while the same CS application at layers II-III induced no LTP in any of the 6 tested slices. Conclusion The rat hindlimb representation of S1 area is likely to have at least 2 patterns of neural circuits on brain slices： one is the intracortical circuit （ICC） formed by interlaminar connections from layers II-III, and the other is the thalamocortical circuit （TCC） mediated by afferent connections from layer IV. Besides, ICC of the S1 area is spatially limited, with less plasticity, while TCC is spatially extensive and exhibits a better plasticity in response to somatosensory afferent stimulation. The present data provide a useful experimental model for further studying microcircuit properties in S1 cortex at the network level in vitro.