Prefrontal but not cerebellar tDCS attenuates renewal of extinguished conditioned eyeblink responses.

An extended neural network is known to underlie extinction learning. As yet, comparatively little is known about the possible contribution of the cerebellum and the dorsolateral prefrontal cortex (dlPFC). In the present study, transcranial direct current stimulation (tDCS) was used to provide further evidence that the dlPFC and the cerebellum are involved in extinction-related processes. A total of 100 young and healthy human participants were randomly assigned to one of five stimulation groups: (1) anodal tDCS of the cerebellum, (2) cathodal tDCS of the cerebellum, (3) anodal tDCS of the dlPFC, (4) cathodal tDCS of the dlPFC, and (5) sham stimulation. Participants underwent delay eyeblink conditioning using an A-B-A/B renewal paradigm. Two different colors of background light (orange and blue) were used as contexts. On day 1, acquisition of conditioned eyeblink responses was performed in context A, followed by extinction in context B. tDCS was applied during extinction. On day 2, extinction recall was tested in contexts A and B with higher incidence of conditioned responses in acquisition context A compared to extinction context B indicating renewal effects. All groups showed significant effects of acquisition of conditioned eyeblink responses and significant effects of extinction. There was no significant difference in extinction between stimulation groups. During extinction recall, renewal effects were present in all groups, except the group which had received anodal tDCS of the dlPFC during extinction. In the present study, no direct effects of dlPFC or cerebellar tDCS were demonstrated on extinction. Anodal tDCS of the dlPFC, but not the cerebellum, resulted in delayed effects on context-related processes of extinction, possibly explained by shifting attention away from the context and towards the conditioned stimulus during extinction learning. Anodal tDCS of the dlPFC attenuated context-related recall of learned aversive responses. Effects of tDCS, however, were weak and need to be confirmed in future studies. Lack of cerebellar tDCS effects do not exclude a possible role of the cerebellum in extinction-related processes, and are likely explained by methodological limitations of cerebellar tDCS.

Fetal magnetocardiography (fMCG) to monitor cardiac time intervals in fetuses at risk for isoimmune AV block.

OBJECTIVE: The objective of this report is to detect cardiac time intervals (CTIs) in fetuses exposed to SSA/Ro-SSB/La antibodies in relation to gestational age (GA) and fetal weight and compared them with a control cohort. METHODS: Fetal magnetocardiography (fMCG) recordings were conducted on a biomagnetic device dedicated to obstetrical measurement starting in the second trimester. Fetal cardiac time intervals of 87 healthy fetuses of normal gestation (control group) were compared to 11 fetuses exposed to maternal SSA/Ro-SSB/La antibodies (study group). RESULTS: fCTIs were analyzed starting at 17 weeks of GA. Atrial and ventricular depolarization times increased with GA in both groups. PQ segments were significantly longer in the study group (50.8 ms vs. 60.2 ms; p < 0.001) independent of GA or fetal weight. PQ segment prolongation was more obvious in the study group prior to 30 weeks of GA. CONCLUSION: PQ segment prolongation can be interpreted as early AV-node involvement caused by maternal SSA/Ro-SSB/La antibodies. The age dependency of the PQ segment should be taken into account in further studies.

Fetal auditory evoked responses to onset of amplitude modulated sounds. A fetal magnetoencephalography (fMEG) study.

The human fetal auditory system is functional around the 25th week of gestational age when the thalamocortical connections are established. Fetal magnetoencephalography (fMEG) provides evidence for fetal auditory brain responses to pure tones and syllables. Fifty-five pregnant women between 31 and 40 weeks of gestation were included in the study. Fetal MEG was recorded during the presentation of an amplitude modulated tone (AM) with a carrier frequency of 500 Hz to the maternal abdomen modulated by low modulation rates (MRs) - 2/s and 4/s, middle MR - 8/s and high MRs - 27/s, 42/s, 78/s and 91/s. The aim was to determine whether the fetal brain responds differently to envelope slopes and intensity change at the onset of the AM sounds. A significant decrease of the response latencies of transient event-related responses (ERR) to high and middle MRs in comparison to the low MRs was observed. The highest fetal response rate was achieved by modulation rates of 2/s, 4/s and 27/s (70%, 57%, and 86%, respectively). Additionally, a maturation effect of the ERR (response latency vs. gestational age) was observed only for 4/s MR. The significant difference between the response latencies to low, middle, and high MRs suggests that still before birth the fetal brain processes the sound slopes at the onset in different integration time-windows, depending on the time for the intensity increase or stimulus power density at the onset, which is a prerequisite for language acquisition.

Human auditory middle latency responses: influence of stimulus type and intensity.

Human auditory middle latency responses (MLR) to click and tone pip stimuli of different intensities were recorded by means of magnetoencephalography (MEG) and electroencephalography (EEG). Clicks elicited larger responses with significantly shorter latencies than the tone pips at the same intensity in dB sensation level (SL). Most MLR amplitudes increased and their latencies decreased with increasing stimulus intensity for both types of stimulation. Pa and Nb amplitudes saturated at intensities of 60 dB SL in the case of click stimulation. The shorter latencies of MLR evoked by the click were explained by its short rise time and the high frequency content of its spectrum. MEG source analysis yielded MLR sources which were clearly different from those of the slow cortical wave N1. They seem to be located in primary auditory areas along Heschl's gyrus.

Assessment of EEG frequency dynamics using complex demodulation.

The complex demodulation (CD) approach was applied to human EEG recorded during a cognitive task performance, including voluntary goal-directed movements. The standard CD algorithm was extended by a simple procedure using frequency histograms and power spectra to select the characteristic frequencies of EEG segments around the task performance. In the majority of records, amplitude modulation was found, which decreased or disappeared in the period prior to and at the very beginning of the task performance. It was found that the decrease of modulation in fast beta and gamma components begins approximately one second before that of the alpha components. Frequency modulation appeared in some records at the end of the task in beta and gamma components. The results showed that a cognitive task performance is accompanied by non-linear processes in the frequency components of EEG. These dynamic changes could extend the findings of event-related desynchronization obtained by linear methods.

The method of linear transformation in revealing EEG polyharmonic components in comparison to the Fourier analysis.

The method of linear transformation (LT) in the modification known as method of Buys Ballot was examined in its ability to reveal polyharmonic periodicities in EEG signals. Applying this method to simulated signals-additive mixtures of sinusoids, periodic squared waves and Gaussian noise some rules were found, which can be used in analyzing of EEG signals. The results were compared to that of Discrete Fourier analysis. The conclusion was made that in contrast to the method of Fourier giving the frequency contents, LT method is able to reveal not only the mono- but also polyharmonic components with their waveshape (the reconstruction) even if their frequency bands are overlapping.

Experimental setup and instrumentation for measurement and preprocessing of EEG during voluntary goal-directed movements.

The widely used practice in the study of human complex voluntary movement organization is to record, measure and analyze EEG activity covering the period of both motor preparation and performance. The main strategy is to reveal EEG characteristics related to both cognitive and motor aspects of the action. To this end a special-purpose experimental set-ups are required providing precise enough measure of timing and characteristics of the movement in order to synchronize EEG changes time-locked to the phases of task performance. We describe an experimental set-up including a special-purpose device, which was designed for study of slow, continuous goal-directed movements. The implementation was aimed to provide (i) performance of complicated enough task in order to force the subject to concentrate his mental activity predominantly on the task; (ii) to control the successive stages of task performance. The advantages of the presented instrumentation was demonstrated by comparing power spectra of EEG segments long before and immediately prior to the movement performance. The instrumentation is flexible enough to be used in a large scale psychophysiological experiments.

A high-precision magnetoencephalographic study of human auditory steady-state responses to amplitude-modulated tones.

The cerebral magnetic field of the auditory steady-state response (SSR) to sinusoidal amplitude-modulated (SAM) tones was recorded in healthy humans. The waveforms of underlying cortical source activity were calculated at multiples of the modulation frequency using the method of source space projection, which improved the signal-to-noise ratio (SNR) by a factor of 2 to 4. Since the complex amplitudes of the cortical source activity were independent of the sensor position in relation to the subject's head, a comparison of the results across experimental sessions was possible. The effect of modulation frequency on the amplitude and phase of the SSR was investigated at 30 different values between 10 and 98 Hz. At modulation frequencies between 10 and 20 Hz the SNR of harmonics near 40 Hz were predominant over the fundamental SSR. Above 30 Hz the SSR showed an almost sinusoidal waveform with an amplitude maximum at 40 Hz. The amplitude decreased with increasing modulation frequency but was significantly different from the magnetoencephalographic (MEG) background activity up to 98 Hz. Phase response at the fundamental and first harmonic decreased monotonically with increasing modulation frequency. The group delay (apparent latency) showed peaks of 72 ms at 20 Hz, 48 ms at 40 Hz, and 26 ms at 80 Hz. The effects of stimulus intensity, modulation depth, and carrier frequency on amplitude and phase of the SSR were also investigated. The SSR amplitude decreased linearly when stimulus intensity or the modulation depth were decreased in logarithmic steps. SSR amplitude decreased by a factor of 3 when carrier frequency increased from 250 to 4000 Hz. From the phase characteristics, time delays were found in the range of 0 to 6 ms for stimulus intensity, modulation depth, and carrier frequency, which were maximal at low frequencies, low intensities, or maximal modulation depth.

[Thermodynamic and kinetic aspects of the hydrolysis of ethyl(R)-2- (benzyloxycarbonylamino)-3-sulfamoylpropionate in the presence of free and immobilized alpha-chymotrypsin]. / Thermodynamische und kinetische Aspekte der Hydrolyse des (R)-2- (Benzyloxycarbonylamino)-3-sulfamoylpropionsäure-ethylesters in Gegenwart von freiem und trägergebundenem alpha-Chymotrypsin.

The hydrolysis of ethyl (R)-2-(benzyloxycarbonylamino)-3-sulfamoylpropionate (blocked cysteic acid S-amide) by native and immobilized alpha-chymotrypsin was studied. The experiments were performed using a constant enzyme/substrate ratio of 1:8 and at a temperature of 10-40 degrees C; the immobilized enzyme was bound to a dialdehyde cellulose matrix. A kinetic equation (Eq.10) was found to be applicable which confirms that the mechanism of the enzyme reaction consists of several stages, irrespective of the enzyme state. The temperature dependence of the reaction velocity was investigated and applied using the Arrhenius equation. The constant value thus obtained for the activating energy showed that the active centres retained their character during immobilization. The differences between the velocities of the reaction with immobilized and with native enzyme corresponded to the different number of active centres during the reaction time. Based on these results a kinetic model of the mechanism of the studied reaction is presented which includes an initial balanced stage of the chemosorption type.

Nuclear inheritance of the biosynthesis of cyclopenin and cyclopenol in Penicillium cyclopium.

Balanced heterokarions were grown from Penicillium cyclopium aux-glu 1, a glutamic acid auxotroph producing benzodiazepine alkaloids of the cyclopenin-cyclopenol group, and P. viridicatum aux-met 1, a methionine auxotroph forming these alkaloids in traces only. In contrast to the hyphae of the parent strains, the hyphae of the heterokarions were dark orange-brown and grew well on media without the auxotrophic factors. In surface cultures they synthesized the benzodiazepine alkaloids cyclopenin and cyclopenol in amounts similar to those formed by the hyphae of P. cyclopium aux-glu 1. From the monokariotic conidiospores of the heterokarions homokariotic daughter strains were obtained which were similar to the parent strains in every respect. Hence no exchange of features of cyclopenin-cyclopenol biosynthesis took place between the parent strains at the stage of the heterokarion. This result indicates that the formation of cyclopenin and cyclopenol in P. cyclopium aux-glu 1 and the nearly complete lack of biosynthesis of these compounds in P. viridicatum aux-met 1 is encoded within the nucleus and is not influenced by plasmic genetic material.