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Stressful events impact memory formation, in particular for emotionally arousing stimuli. Although these stress effects on emotional memory formation have potentially far-reaching implications, the underlying neural mechanisms are not fully understood. Specifically, the temporal processing dimension of the mechanisms involved in emotional memory formation under stress remains elusive. Here, we used magnetoencephalography (MEG) to examine the neural processes underlying stress effects on emotional memory formation with high temporal and spatial resolution and a particular focus on theta oscillations previously implicated in mnemonic binding. Healthy participants (n = 53) underwent a stress or control procedure before encoding emotionally neutral and negative pictures, while MEG was recorded. Memory for the pictures was probed in a recognition test 24 h after encoding. In this recognition test, stress did not modulate the emotional memory enhancement but led to significantly higher confidence in memory for negative compared to neutral stimuli. Our neural data revealed that stress increased memory-related theta oscillations specifically in medial temporal and occipito-parietal regions. Further, this stress-related increase in theta power emerged during memory formation for emotionally negative but not for neutral stimuli. These findings indicate that acute stress can enhance, in the medial temporal lobe, oscillations at a frequency that is ideally suited to bind the elements of an ongoing emotional episode, which may represent a mechanism to facilitate the storage of emotionally salient events that occurred in the context of a stressful encounter.

The functional relevance of crossmodal activation (e.g. auditory activation of occipital brain regions) in congenitally blind individuals is still not fully understood. The present study tested whether the occipital cortex of blind individuals is integrated into a challenged functional network. A working memory (WM) training over four sessions was implemented. Congenitally blind and matched sighted participants were adaptively trained with an n-back task employing either voices (auditory training) or tactile stimuli (tactile training). In addition, a minimally demanding 1-back task served as an active control condition. Power and functional connectivity of EEG activity evolving during the maintenance period of an auditory 2-back task were analyzed, run prior to and after the WM training. Modality-specific (following auditory training) and modality-independent WM training effects (following both auditory and tactile training) were assessed. Improvements in auditory WM were observed in all groups, and blind and sighted individuals did not differ in training gains. Auditory and tactile training of sighted participants led, relative to the active control group, to an increase in fronto-parietal theta-band power, suggesting a training-induced strengthening of the existing modality-independent WM network. No power effects were observed in the blind. Rather, after auditory training the blind showed a decrease in theta-band connectivity between central, parietal, and occipital electrodes compared to the blind tactile training and active control groups. Furthermore, in the blind auditory training increased beta-band connectivity between fronto-parietal, central and occipital electrodes. In the congenitally blind, these findings suggest a stronger integration of occipital areas into the auditory WM network.

Pathological synchronisation of beta frequency (12–35 Hz) oscillations between the subthalamic nucleus (STN) and cerebral cortex is thought to contribute to motor impairment in Parkinson's disease (PD). For this cortico-subthalamic oscillatory drive to be mechanistically important, it must influence the firing of STN neurons and, consequently, their downstream targets. Here, we examined the dynamics of synchronisation between STN LFPs and units with multiple cortical areas, measured using frontal ECoG, midline EEG and lateral EEG, during rest and movement. STN neurons lagged cortical signals recorded over midline (over premotor cortices) and frontal (over prefrontal cortices) with stable time delays, consistent with strong corticosubthalamic drive, and many neurons maintained these dynamics during movement. In contrast, most STN neurons desynchronised from lateral EEG signals (over primary motor cortices) during movement and those that did not had altered phase relations to the cortical signals. The strength of synchronisation between STN units and midline EEG in the high beta range (25–35 Hz) correlated positively with the severity of akinetic-rigid motor symptoms across patients. Together, these results suggest that sustained synchronisation of STN neurons to premotor-cortical beta oscillations play an important role in disrupting the normal coding of movement in PD., Highlights • Multi-channel EEG with coincident STN single unit and local field potential recordings • Variable time delays between beta oscillations in different cortical areas and STN neurons. • Frontal/premotor cortical areas have most stable oscillatory synchronisation with STN neurons. • Correlation between cortico-subthalamic beta-frequency synchronisation and clinical scores in PD.

Facial expressions attract attention due to their motivational significance. Previous work focused on attentional biases towards threat-related, fearful faces, although healthy participants tend to avoid mild threat. Growing evidence suggests that neuronal gamma (30Hz) and alpha-band activity (8-12Hz) play an important role in attentional selection, but it is unknown if such oscillatory activity is involved in the guidance of attention through facial expressions. Thus, in this magnetoencephalography (MEG) study we investigated whether attention is shifted towards or away from fearful faces and characterized the underlying neuronal activity in these frequency ranges in forty-four healthy volunteers. We employed a covert spatial attention task using neutral and fearful faces as task-irrelevant distractors and emotionally neutral Gabor patches as targets. Participants had to indicate the tilt direction of the target. Analysis of the neuronal data was restricted to the responses to target Gabor patches. We performed statistical analysis at the sensor level and used subsequent source reconstruction to localize the observed effects. Spatially selective attention effects in the alpha and gamma band were revealed in parieto-occipital regions. We observed an attentional cost of processing the face distractors, as reflected in lower task performance on targets with short stimulus onset asynchrony (SOA150ms) between faces and targets. On the neuronal level, attentional orienting to face distractors led to enhanced gamma band activity in bilateral occipital and parietal regions, when fearful faces were presented in the same hemifield as targets, but only in short SOA trials. Our findings provide evidence that both top-down and bottom-up attentional biases are reflected in parieto-occipital gamma-band activity.

Cross-frequency coupling (CFC) has been suggested to constitute a highly flexible mechanism for cortical information gating and processing, giving rise to conscious perception and various higher cognitive functions in humans. In particular, it might provide an elegant tool for information integration across several spatiotemporal scales within nested or coupled neuronal networks. However, it is currently unknown whether low-frequency (theta/alpha) or high-frequency gamma oscillations orchestrate cross-frequency interactions, raising the question of who is master and who is slave. While correlative evidence suggested that at least two distinct CFC modes exist, namely, phase-amplitude-coupling (PAC) and amplitude-envelope correlations (AEC), it is currently unknown whether they subserve distinct cortical functions. Novel non-invasive brain stimulation tools, such as transcranial alternating current stimulation (tACS), now provide the unique opportunity to selectively entrain the low- or high-frequency component and study subsequent effects on CFC. Here, we demonstrate the differential modulation of CFC during selective entrainment of alpha or gamma oscillations. Our results reveal that entrainment of the low-frequency component increased PAC, where gamma power became preferentially locked to the trough of the alpha oscillation, while gamma-band entrainment enhanced AECs and reduced alpha power. These results provide causal evidence for the functional role of coupled alpha and gamma oscillations for visual processing.

Sleep spindles are crucial to memory consolidation. Cortical gamma oscillations (30–100 Hz) are considered to reflect processing of memory in local cortical networks. The temporal and regulatory relationship between spindles and gamma activity might therefore provide clues into how sleep strengthens cortical memory representations. Here, combining EEG with MEG recordings during sleep in healthy humans (n = 12), we investigated the temporal relationships of cortical gamma band activity, always measured by MEG, during fast (12–16 Hz) and slow (8–12 Hz) sleep spindles detected in the EEG or MEG. Time-frequency distributions did not show a consistent coupling of gamma to the spindle oscillation, although activity in the low gamma (30–40 Hz) and neighboring beta range (

Loss-of-function mutations in the parkin-encoding PARK2 gene are a frequent cause of young-onset, autosomal recessive Parkinson's disease (PD). Parkin knockout mice have no nigro-striatal neuronal loss but exhibit abnormalities of striatal dopamine transmission and cortico-striatal synaptic function. How these predegenerative changes observed in vitro affect neural dynamics at the intact circuit level, however, remains hitherto elusive. Here, we recorded from motor cortex, striatum and globus pallidus (GP) of anesthetized parkin-deficient mice to assess cortex-basal ganglia circuit dynamics and to dissect cell type-specific functional connectivity in the presymptomatic phase of genetic PD. While ongoing activity of presumed striatal spiny projection neurons and their downstream counterparts in the GP was not different from controls, parkin deficiency had a differential impact on striatal interneurons: In parkin-mutant mice, tonically active neurons displayed elevated activity levels. Baseline firing rates of transgenic striatal fast spiking interneurons (FSI), on the contrary, were reduced and the correlational structure of the FSI microcircuitry was disrupted. The entire transgenic striatal microcircuit showed enhanced and phase-shifted phase coupling to slow (1-3 Hz) cortical population oscillations. Unexpectedly, local field potentials recorded from striatum and GP of parkin-mutant mice robustly displayed amplified beta oscillations (~22 Hz), phase-coupled to cortex. Parkin deficiency selectively increased spike-field coupling of FSIs to beta oscillations. Our findings suggest that loss of parkin function leads to amplifications of synchronized cortico-striatal oscillations and an intrastriatal reconfiguration of interneuronal circuits. This presymptomatic disarrangement of dynamic functional connectivity may precede nigro-striatal neurodegeneration and predispose to imbalance of striatal outflow accompanying symptomatic PD.

Coherent percepts emerge from the accurate combination of inputs from the different sensory systems. There is an ongoing debate about the neurophysiological mechanisms of crossmodal interactions in the brain, and it has been proposed that transient synchronization of neurons might be of central importance. Oscillatory activity in lower frequency ranges (< 30 Hz) has been implicated in mediating long-range communication as typically studied in multisensory research. In the current study, we recorded high-density electroencephalograms while human participants were engaged in a visuotactile pattern matching paradigm and analyzed oscillatory power in the theta- (4-7 Hz), alpha- (8-13 Hz) and beta-bands (13-30 Hz). Employing the same physical stimuli, separate tasks of the experiment either required the detection of predefined targets in visual and tactile modalities or the explicit evaluation of crossmodal stimulus congruence. Analysis of the behavioral data showed benefits for congruent visuotactile stimulus combinations. Differences in oscillatory dynamics related to crossmodal congruence within the two tasks were observed in the beta-band for crossmodal target detection, as well as in the theta-band for congruence evaluation. Contrasting ongoing activity preceding visuotactile stimulation between the two tasks revealed differences in the alpha- and beta-bands. Source reconstruction of between-task differences showed prominent involvement of premotor cortex, supplementary motor area, somatosensory association cortex and the supramarginal gyrus. These areas not only exhibited more involvement in the pre-stimulus interval for target detection compared to congruence evaluation, but were also crucially involved in post-stimulus differences related to crossmodal stimulus congruence within the detection task. These results add to the increasing evidence that low frequency oscillations are functionally relevant for integration in distributed brain networks, as demonstrated for crossmodal interactions in visuotactile pattern matching in the current study.

Zusammenfassung Intraoperative Mikroelektrodenableitungen werden eingesetzt, um die Prazision funktionell-neurochirurgischer Eingriffe zu erhohen. Ihr Haupteinsatzgebiet sind die gezielten Hirnoperationen im Rahmen der Tiefen Hirnstimulation zur Behandlung schwerer Bewegungsstorungen wie Morbus Parkinson, Dystonie oder therapierefraktarer Tremorformen. Dieser Artikel beschreibt die typischen elektrophysiologischen Befunde in den drei wichtigsten subkortikalen Zielgebieten in der funktionellen Neurochirurgie bei Bewegungsstorungen: Nucleus subthalamicus, Globus pallidus internus und Nucleus ventro-intermedius thalami.

Tactile localization entails the transformation of the initial skin-based location into an external reference frame that accounts for body posture and subsequent flexible integration of these two reference frames. The mechanisms underlying this tactile remapping are not well understood. Notably, there is a gap between the principles uncovered by psychophysical research and the mechanistic explanations offered by neuroscientific studies. We suggest that spatial localization is best viewed as a process of integrating multiple concurrently active spatial representations rather than a sequential transformation process. To achieve integration, large-scale interactions are required that link these different representations. Coordinated oscillatory activity may be a suitable mechanism that allows parallel representation of multiple spatial formats and the formation of an integrated location estimate.

Objective While motor effects of dopaminergic medication and subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson’s disease (PD) patients are well explored, their effects on sensory processing are less well understood. Here, we studied the impact of levodopa and STN-DBS on auditory processing. Methods Rhythmic auditory stimulation (RAS) was presented at frequencies between 1 and 6 Hz in a passive listening paradigm. High-density EEG-recordings were obtained before (levodopa ON/OFF) and 5 months following STN-surgery (ON/OFF STN-DBS). We compared auditory evoked potentials (AEPs) elicited by RAS in 12 PD patients to those in age-matched controls. Tempo-dependent amplitude suppression of the auditory P1/N1-complex was used as an indicator of auditory gating. Results Parkinsonian patients showed significantly larger AEP-amplitudes (P1, N1) and longer AEP-latencies (N1) compared to controls. Neither interruption of dopaminergic medication nor of STN-DBS had an immediate effect on these AEPs. However, chronic STN-DBS had a significant effect on abnormal auditory gating characteristics of parkinsonian patients and restored a physiological P1/N1-amplitude attenuation profile in response to RAS with increasing stimulus rates. Conclusions This differential treatment effect suggests a divergent mode of action of levodopa and STN-DBS on auditory processing. Significance STN-DBS may improve early attentive filtering processes of redundant auditory stimuli, possibly at the level of the frontal cortex.

Cortex-basal ganglia circuits participate in motor timing and temporal perception, and are important for the dynamic configuration of sensorimotor networks in response to exogenous demands. In Parkinson's disease (PD) patients, rhythmic auditory stimulation (RAS) induces motor performance benefits. Hitherto, little is known concerning contributions of the basal ganglia to sensory facilitation and cortical responses to RAS in PD. Therefore, we conducted an EEG study in 12 PD patients before and after surgery for subthalamic nucleus deep brain stimulation (STN-DBS) and in 12 age-matched controls. Here we investigated the effects of levodopa and STN-DBS on resting-state EEG and on the cortical-response profile to slow and fast RAS in a passive-listening paradigm focusing on beta-band oscillations, which are important for auditory–motor coupling. The beta-modulation profile to RAS in healthy participants was characterized by local peaks preceding and following auditory stimuli. In PD patients RAS failed to induce pre-stimulus beta increases. The absence of pre-stimulus beta-band modulation may contribute to impaired rhythm perception in PD. Moreover, post-stimulus beta-band responses were highly abnormal during fast RAS in PD patients. Treatment with levodopa and STN-DBS reinstated a post-stimulus beta-modulation profile similar to controls, while STN-DBS reduced beta-band power in the resting-state. The treatment-sensitivity of beta oscillations suggests that STN-DBS may specifically improve timekeeping functions of cortical beta oscillations during fast auditory pacing., Highlights • High density EEG investigation in patients with PD before and after STN-DBS surgery • Resting state EEG: altered spectral composition following STN-DBS • Rhythmic auditory stimulation (RAS): absence of pre-stimulus beta activity in PD • Fast RAS: normalization of beta (13–30 Hz) activities by L-DOPA and STN-DBS • Altered beta modulation profile may contribute to timekeeping deficits in PD.

Summary Novel methods for neuronal entrainment [1–4] provide the unique opportunity to modulate perceptually relevant brain oscillations [5, 6] in a frequency-specific manner and to study their functional impact on distinct cognitive functions. Recently, evidence has emerged that tACS (transcranial alternating current stimulation) can modulate cortical oscillations [7–9]. However, the study of electrophysiological effects has been hampered so far by the absence of concurrent electroencephalogram (EEG) recordings. Here, we applied 10 Hz tACS to the parieto-occipital cortex and utilized simultaneous EEG recordings to study neuronal entrainment during stimulation. We pioneer a novel approach for simultaneous tACS-EEG recordings and successfully separate stimulation artifacts from ongoing and event-related cortical activity. Our results reveal that 10 Hz tACS increases parieto-occipital alpha activity and synchronizes cortical oscillators with similar intrinsic frequencies to the entrainment frequency. Additionally, we demonstrate that tACS modulates target detection performance in a phase-dependent fashion highlighting the causal role of alpha oscillations for visual perception.

Intrinsic coupling constitutes a key feature of ongoing brain activity, which exhibits rich spatiotemporal patterning and contains information that influences cognitive processing. We discuss evidence for two distinct types of intrinsic coupling modes which seem to reflect the operation of different coupling mechanisms. One type arises from phase coupling of band-limited oscillatory signals, whereas the other results from coupled aperiodic fluctuations of signal envelopes. The two coupling modes differ in their dynamics, their origins, and their putative functions and with respect to their alteration in neuropsychiatric disorders. We propose that the concept of intrinsic coupling modes can provide a unifying framework for capturing the dynamics of intrinsically generated neuronal interactions at multiple spatial and temporal scales.

Intelligent agents must select and apply rules to accomplish their goals. In this issue of Neuron, Buschman et al. (2012) demonstrate that oscillatory neuronal coupling is key to rule processing in monkey prefrontal cortex, notably when rules change during tasks.

SummaryIntrinsic cortical dynamics modulates the processing of sensory information and therefore may be critical for conscious perception [1–3]. We tested this hypothesis by electroencephalographic recording of ongoing and stimulus-related brain activity during stepwise drug-induced loss of consciousness in healthy human volunteers. We found that progressive loss of consciousness was tightly linked to the emergence of a hypersynchronous cortical state in the alpha frequency range (8–14 Hz). This drug-induced ongoing alpha activity was widely distributed across the frontal cortex. Stimulus-related responses to median nerve stimulation consisted of early and midlatency response components in primary somatosensory cortex (S1) and a late component also involving temporal and parietal regions. During progressive sedation, the early response was maintained, whereas the midlatency and late responses were reduced and eventually vanished. The antagonistic relation between the late sensory response and ongoing alpha activity held for constant drug levels on the single-trial level. Specifically, the late response component was negatively correlated with the power and long-range coherence of ongoing frontal alpha activity. Our results suggest blocking of intracortical communication by hypersynchronous ongoing activity as a key mechanism for the loss of consciousness.

Alcohol addiction is associated with alterations of central nervous dopaminergic and serotonergic functions. Acute tryptophan depletion has not yet been applied in detoxified alcohol-addicted patients in order to investigate its impact on psychopathology, psychoneuroendocrinology, and substance craving behaviour. 25 alcohol-addicted males randomly either received a tryptophan-free or tryptophan-containing amino acid drink and 7 days later the respective other drink. Anxiety, depression, and craving were assessed before and 5 h after the drink. Tryptophan, 5-HIAA, dopamine, norepinephrine, epinephrine, and HVA in serum were measured before and after both treatments. Nocturnal urinary cortisol measurements and genotyping for the HTTLPR polymorphism of the SLC6A4 gene were performed. Tryptophan depletion resulted in a significant reduction of total and free serum tryptophan while the tryptophan-rich drink increased serum levels. Both treatments caused a significant increase of serum serotonin levels, however, serum 5-HIAA was decreased after depletion but increased after sham depletion. Dopamine and norepinephrine were elevated after tryptophan depletion and sham. Depletion increased depression scores (MADRS), while the full amino acid drink improved state and trait anxiety ratings (STAI) and substance craving. Urinary cortisol excretion was not affected by both treatments. Patients with the ll genotype of the serotonin transporter gene displayed lower baseline tryptophan levels compared to patients with the heterozygous genotype. Results suggest an impaired serotonergic function in alcohol-addicted males.

Contains fulltext : 71012.pdf (Publisher’s version ) (Closed access) Oscillatory neuronal synchronization, within and between cortical areas, may mediate the selection of attended visual stimuli. However, it remains unclear at and between which processing stages visuospatial attention modulates oscillatory synchronization in the human brain. We thus combined magnetoencephalography (MEG) in a spatially cued motion discrimination task with source-reconstruction techniques and characterized attentional effects on neuronal synchronization across key stages of the human dorsal visual pathway. We found that visuospatial attention modulated oscillatory synchronization between visual, parietal, and prefrontal cortex in a spatially selective fashion. Furthermore, synchronized activity within these stages was selectively modulated by attention, but with markedly distinct spectral signatures and stimulus dependence between regions. Our data indicate that regionally specific oscillatory synchronization at most stages of the human dorsal visual pathway may enhance the processing of attended visual stimuli and suggest that attentional selection is mediated by frequency-specific synchronization between prefrontal, parietal, and early visual cortex.

Usnea barbata and its major constituent usnic acid are potent antimicrobial agents. Here, we have investigated anti-inflammatory properties of an U. barbata extract (UBE) containing 4% usnic acid in an ultraviolet-B (UVB) model with HaCaT keratinocytes. UVB irradiation induced PGE 2 production and COX-2 expression in a time and dose-dependent manner. UBE inhibited PGE 2 production at a half-maximal concentration of 60 μg/ml (2.4 μg/ml usnic acid) that did not affect the UVB-induced upregulation of COX-2, suggesting an effect on enzyme activity rather than on protein expression. The inhibition of PGE 2 production by UBE was not due to cytotoxicity. Besides its known antimicrobial properties, UBE displays specific UVB protective effects that might be useful in the topical treatment of UVB-mediated inflammatory skin conditions.

We investigated the effects of expectation on intensity ratings and somatosensory evoked magnetic fields and electrical potentials following painful infrared laser stimuli in six healthy subjects. The stimulus series contained trials preceded by different auditory cues which either contained valid, invalid or no information about the upcoming laser intensity. High and low intensities occurred equally probable across cue types. High intensity stimuli induced greater pain than low intensity across all cue types. Furthermore, laser intensity significantly interacted with cue validity: high intensity stimuli were perceived less painful and low intensity stimuli more painful following invalid compared to valid cues. The amplitude of the evoked magnetic field localized within the contralateral secondary somatosensory cortex (SII) at about 165 ms after laser stimuli varied also both with stimulus intensity and cue validity. The evoked electric potential peaked at about 300 ms after laser stimuli and yielded a single dipole source within a region encompassing the caudal anterior cingulate cortex and posterior cingulate cortex. Its amplitude also varied with stimulus intensity, but failed to show any cue validity effects. This result suggests a priming of early cortical nociceptive sensitivity by cues signaling pain severity. A possible contribution of the SII cortex to the manifestation of nocebo/placebo cognitions is discussed.

To better understand whether voluntary attention affects how the brain processes novel events, variants of the auditory novelty oddball paradigm were presented to two different groups of human volunteers. One group of subjects (n=16) silently counted rarely presented 'infrequent' tones (p=0.10), interspersed with 'novel' task-irrelevant unique environmental sounds (p=0.10) and frequently presented 'standard' tones (p=0.80). A second group of subjects (n=17) silently counted the 'novel' environmental sounds, the 'infrequent' tones now serving as the task-irrelevant deviant events. Analysis of event-related potentials (ERPs) recorded from 63 scalp channels suggested a spatiotemporal overlap of fronto-central novelty P3 and centro-parietal P3 (P3b) ERP features in both groups. Application of independent component analysis (ICA) to concatenated single trials revealed two independent component clusters that accounted for portions of the novelty P3 and P3b response features, respectively. The P3b-related ICA cluster contributed to the novelty P3 amplitude response to novel environmental sounds. In contrast to the scalp ERPs, the amplitude of the novelty P3 related cluster was not affected by voluntary attention, that is, by the target/nontarget distinction. This result demonstrates the usefulness of ICA for disentangling spatiotemporally overlapping ERP processes and provides evidence that task irrelevance is not a necessary feature of novelty processing.

Objective: The effects of stimulus size, duration and eccentricity on the visual gamma-band response (GBR) in human EEG were investigated and compared to visual evoked potentials (VEPs) in order to differentiate in future (and past) experiments whether changes in GBRs are due to stimulus-related (exogenous) or cognitive effects. Methods: EEG was recorded from 23 subjects while they performed a simple choice reaction time task requiring discrimination of squares and circles. In separate blocks stimulus size, duration, and eccentricity were manipulated. EEG was recorded from 64 electrodes. A wavelet transform based on Morlet wavelets was employed for the analysis of gamma-band activity. Results: Amplitude of the GBR was diminished for small and peripheral stimuli. With short stimulus durations ON and OFF responses of the GBR merged into one peak. In comparison, VEP amplitudes were less susceptible to stimulus features. In contrast to VEP latencies, however, GBR latency did not show a lateralization for eccentric stimuli. Conclusions: In addition to previous experiments which have shown a modulation of the GBR by various cognitive processes, the present results demonstrate the susceptibility of the GBR in human EEG to exogenous factors, as numerous intracortical recordings in non-human primates have shown before. The results suggest that the human GBR resides in early visual areas. Significance: The demonstration of the susceptibility of the GBR to stimulus properties implies that studies aimed at exploring the involvement of the GBR in information processing have to be designed carefully. It also constrains the localization of the human GBR. q 2004 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Oscillatory neural activity in the gamma frequency range (>30 Hz) has been shown to accompany a wide variety of cognitive processes. So far, there has been limited success in assigning a unitary basic function to these oscillations, and critics have raised the argument that they could just be an epiphenomenon of neural processing. We propose a new framework that relates gamma oscillations observed in human, as well as in animal, experiments to two underlying processes: the comparison of memory contents with stimulus-related information and the utilization of signals derived from this comparison. This model attempts to explain early gamma-band responses in terms of the match between bottom-up and top-down information. Furthermore, it assumes that late gamma-band activity reflects the readout and utilization of the information resulting from this match.

Target point accuracy is a main issue in functional stereotactic procedures for the implantation of deep brain stimulators. Next to standard stereotactic methods, intraoperative microelectrode recordings help to reach the target point. While currently up to 5 electrodes are used, we introduce a new 32-channel system. Our probes allow for recording 32 neural signals alongside up to 1 cm of the planned trajectory simultaneously. The signal evaluation is supported by customized analysis and visualization tools contained in our navEgate DAQ software. The acquisition software has access to the navEbase database that holds characteristic signal features with respect to their anatomic origin. Currently recorded signals can be compared against nominal values from the database. While preclinical studies of our system are on the way, we are convinced that the possibility to record neural depth profiles will fasten intrapoerative microelectrode recordings, and that the feedback from navEbase will assist teams in questionable cases.

b Abstract An auditory novelty-oddball task, which is known to evoke a P3 event-related potential (ERP) in a target condition and a novelty-P3 ERP in response to task-irrelevant unique environmental sounds, was repeatedly applied to healthy participants (ns14) on two separate recording sessions, 7 days apart. Both target-P3 and novelty-P3 were internally consistent and test-retest reliable. Interestingly, novelty-P3 amplitude declined from the first to the second half of each recording session, whereas no systematic alteration between both sessions occurred. The target-P3 showed the opposite pattern, i.e. a reduced amplitude from the first to the second session, but no systematic change within each session. These findings suggest that novelty-P3 amplitude changes reflect habituation, whereas target-P3 session effects may indicate the adjusted amount of processing resources invested into the task. In general, the results support the interpretation of the novelty-P3 as indicating automatic, bottom-up related aspects of attention, whereas the target-P3, in the present paradigm, seems to reflect voluntary, top-down related aspects of attention. 2002 Elsevier Science B.V. All rights reserved.

Protein stability, as measured by irreversible protein aggregation, is one of the central difficulties in the handling of detergent-solubilized membrane proteins. We present a quantitative analysis of the stability of the Escherichia coli lactose (lac) permease and a series of lac permease fusion proteins containing an insertion of cytochromeb562, T4 lysozyme or β-lactamase in the central hydrophilic loop of the permease. The stability of the proteins was evaluated under a variety of storage conditions by both a qualitative SDS-PAGE assay and by a quantitative hplc assay. Long-chain maltoside detergents were more effective at maintaining purified protein in solution than detergents with smaller head groups and/or shorter alkyl tails. A full factorial experiment established that the proteins were insensitive to sodium chloride concentrations, but greatly stabilized by glycerol, low temperature and the combination of glycerol and low temperature. The accurate quantitation of the protein by absorbance spectroscopy required exclusion of all contact with clarified polypropylene or polyvinyl chloride (PVC) materials. Although some of the fusion proteins were more prone to aggregation than the wild-type permease, the stability of a fusion protein containing a cytochromeb562 insertion was indistinguishable from that of native lac permease.

Item does not contain fulltext Ocular dominance in extrastriate visual cortex of cats with behaviorally defined strabismic amblyopia was studied using extracellular recording techniques. In area 18, the amblyopic eye drove about as many cells as the normal one. In area posteromedial lateral suprasylvian area (PMLS), about 60% of the cells responded exclusively to stimulation of the normal eye and 30% to stimulation of the amblyopic eye. In area 21a more than 75% of the cells were monocularly driven by the non-amblyopic eye while only 5% were monocularly driven by the amblyopic eye. These findings suggest that ventral pathways (area 21a) are more affected in amblyopia than dorsal pathways (area PMLS).

The article reports on the Xe ion beam irradiation studies of Ni3N/Al bilayers at 80 K. The ion-induced modifications were monitored by Rutherford backscattering (RBS), resonant nuclear reaction analysis (RNRA), X-ray diffraction (XRD) and atomic force microscopy (AFM). We found preferential loss of nitrogen from the surface region of the Ni3N top layers. The surface roughness ΔσS and the interface broadening variance Δσint2 increase linearly with the Xe ion fluence Φ. The experimental mixing rate of Δσ 2 /Φ=1.8 nm 4 is explained by considering an enhancement of ballistic mixing due to chemical reactions at the interface.

Nitrides, carbides and oxides are important ceramic materials for wide range of applications in coating, nuclear reactor and semiconductor technology. The study of their bonding properties to metals and semiconductors, for instance via ion irradiation, is of great importance. In this work, we report on the effects induced by 100 and 450 keV Xe+ ions in 70–100 nm Ni3N layers deposited on Si substrates. Low-energy irradiation at 80 K was found to cause a preferential nitrogen loss in the near-surface regions and an increase in surface roughness of the Ni3N film. After the 450 keV Xe+ ion irradiation, strong mixing and the formation of Ni2Si and Si3N4 phases were detected at the Ni3N/Si interface. These findings demonstrate the dissociation of Ni3N under ion bombardment and the competition of chemical driving forces and collision cascade mixing at the interface.

The dimeric, peroxisomal 3-ketoacyl-CoA thiolase catalyses the conver- sion of 3-ketoacyl-CoA into acyl-CoA, which is shorter by two carbon atoms. This reaction is the last step of the b-oxidation pathway. The crys- tal structure of unliganded peroxisomal thiolase of the yeast Saccharo- myces cerevisiae has been refined at 1.8 Aresolution. An unusual feature of this structure is the presence of two helices, completely buried in the dimer and sandwiched between two b-sheets. The analysis of the struc- ture shows that the sequences of these helices are not hydrophobic, but generate two amphipathic helices. The helix in the N-terminal domain exposes the polar side-chains to a cavity at the dimer interface, filled with structured water molecules. The central helix in the C-terminal domain exposes its polar residues to an interior polar pocket. The refined structure has also been used to predict the mode of binding of the sub- strate molecule acetoacetyl-CoA, as well as the reaction mechanism. From previous studies it is known that Cys125, His375 and Cys403 are important catalytic residues. In the proposed model the acetoacetyl group fits near the two catalytic cysteine residues, such that the oxygen atoms point towards the protein interior. The distance between SG(Cys125) and C3(acetoacetyl-CoA) is 3.7 A ˚ . The O2 atom of the docked acetoacetyl group makes a hydrogen bond to N(Gly405), which would favour the formation of the covalent bond between SG(Cys125) and C3(acetoacetyl-CoA) of the intermediate complex of the two-step reaction. The CoA moiety is proposed to bind in a groove on the surface of the protein molecule. Most of the interactions of the CoA molecule are with atoms of the loop domain. The three phosphate groups of the CoA moi- ety are predicted to interact with side-chains of lysine and arginine resi- dues, which are conserved in the dimeric thiolases. # 1997 Academic Press Limited

Combined arc/unbalanced magnetron (ABS™) PVD hard coating technology has been available to the hard coating market for five years with the industrial coating system HTC-1000-ABS-MK I. Besides an improved HTC-1000-ABS-MK II version the HTC-1500-ABS is available now, with a four-fold production capacity of that of the original model. In the HTC-1500-ABS six cathode positions are integrated into the two large doors of the typically octagon-shaped vacuum chamber. The positions can be used to mount either Arc or UBM cathodes as needed for the type of coating that will be deposited. The length of the cathodes is 1700mm and individual shutters minimize cross contamination in the multitarget unit. In UBM mode, the degree of ionisation is controlled by electromagnets. Four 22001/s turbo molecular pumps in combination with a 1000 m3/h roots and a 250 m3/h rotary vane pump guarantee sufficient high gas throughput and short pumping periods. Reactive gas control can be carried out by high accuracy Viscovac total pressure control. A constant process temperature is achieved by powerful radiative heaters. Substrate fixturing is carried out using roll-in/roll-out, two-or three-fold rotating turntables. The diameter of the substrate turntable is 900 mm with an effective coating height of 1500 mm. Principal applications are temperature coatings, including decorative and automotive applications. The unit is especially suited to further promote PVD as an environmentally friendly coating technology.

Objective During recent years, extensive studies in different genetic model systems have complemented conventional toxin-based dopamine depletion approaches and significantly advanced our pathophysiological understanding of familial Parkinson’s disease (PD) from a molecular level to human clinical practice. One of the particular strengths of genetic models is that they open experimental windows to hitherto inaccessible presymptomatic periods in PD, allowing for an investigation of functional changes and adaptive mechanisms during very early phases of this complex neurodegenerative disorder. Mice with a loss-of-function mutation in the parkin-encoding PARK2 gene (a frequent cause of young-onset, autosomal recessive PD) display no motor symptoms, show no appreciable dopaminergic neurodegeneration but exhibit abnormalities of striatal dopaminergic neurotransmission and impaired signalling at the cortico-striatal synapse. Here, we set out to determine whether and how loss of parkin function affects neuronal activity in cortex-basal ganglia networks in vivo. Methods To dissect the cortico-striato-pallidal circuitry in this premanifest model of PD, we performed simultaneous microelectrode recordings in motor cortex, striatum and globus pallidus of anesthetized parkin-mutant mice and controls. Results Based on electrophysiological criteria of striatal single unit activity, we identified several presumably different striatal cell types: Medium spiny projection neurons (pMSN), tonically active neurons (pTAN – corresponding to cholinergic interneurons) and fast spiking interneurons (pFSI – a subpopulation of GABAergic interneurons). In transgenic mice, pTANs displayed significantly increased activity levels, while pFSIs showed reduced discharge rates compared to controls. Furthermore, we found evidence for a disrupted functional connectivity within the striatal FSI microcircuit. In line with the absence of motor symptoms, we observed no changes in the ongoing discharge characteristics of transgenic pMSNs and pallidal neurons. Phase locking analysis revealed elevated and phase-shifted phase coupling to slow (1–3 Hz) cortical local field potential oscillations. Unexpectedly, local field potentials recorded from striatum and globus pallidus of parkin-mutant mice robustly exhibited amplified beta oscillations. Notably, the subgroup of pFSIs showed a selective enhancement of phase coupling to these beta oscillations. Conclusions Our findings suggest that loss of parkin function leads to amplifications of synchronized cortico-striatal oscillations in multiple frequency ranges and an intrastriatal reconfiguration of interneuronal circuits. This presymptomatic disarrangement of striatal dynamic functional connectivity may precede nigrostriatal neurodegeneration and predispose to imbalance of striatal outflow accompanying symptomatic PD.

Omp alpha is an outer-membrane protein that spans the periplasmic space of the hyperthermophilic eubacterium Thermotoga maritima. The molecule contains a globular head with an apparent diameter of 8 nm and a rod-shaped tail of 40 nm length. The sequence of the globular domain is homologous to a conserved region of cell wall-bound proteins and probably attaches Omp alpha to the peptidoglycan. The sequence of the rod domain resembles that of coiled coil proteins and ends in a transmembrane segment that anchors Omp alpha to the outer membrane. We have analysed Omp alpha by scanning transmission electron microscopy (STEM) and by statistical sequence analysis methods. The Omp alpha rod is a tetramer with an unusual periodicity of hydrophobic residues close to 3.6 that differs from the 3.5 periodicity of canonical coiled coils. This is due to periodic omissions of three residues in the heptad repeat pattern ("stutters") whose effect is to locally distort the packing of hydrophobic layers in the core of the coiled coil. Residues in position alpha are shifted to occupy a position halfway between positions alpha and d (x layers) and residues in positions d and e are shifted so that both participate in core packing interactions (da layers). Such distorted layers are frequently found in helical bundles and are characteristic of helices that do not undergo supercoiling. The only homo-oligomeric coiled coil of known structure which contains x and da layers is the three-stranded coiled coil of influenza haemagglutinin. Using geometric constraints derived from this structure, we have built a model for the Omp alpha rod in which the helices have a crossing angle of less than 15 degrees and maintain a residual degree of supercoiling with a pitch of approximately 40 nm. Our analysis of distorted layers in the hydrophobic core of coiled coils and helical bundles shows that stutters must not be viewed as discontinuities but rather as a departure from the canonical "knobs-into-holes" packing that allows helices to interact at a low angle without supercoiling. Although stutters have been considered to weaken helical interactions, their occurrence in a rigid, highly thermostable coiled coil indicates that this may not be generally true. Our analysis also indicates that skips and stutters are two different conventions for describing the same underlying structural feature.

We report the first results of the AMANDA detector. During the antarctic summer 1993-94 four strings were deployed between 0.8 an 1 km depth, each equipped with 20 photomultiplier tubes (PMTs). A laser source was used to investigate the optical properties of the ice in situ. We find that the ice is intrinsically extremely transparent. The measured absorption length is 59 ± 3 m, i.e. comparable with the quality of the ultra-pure water used in the IMB and Kamiokande proton-decay and neutrino experiments [1,2] and more than two times longer than the best value reported for laboratory ice [3]. Due to a residual density of air bubbles at these depths, the motion of photons in the medium is randomized. For spherical, smooth bubbles we find that, at 1 km depth, the average distance between collisions is about 25 cm. The measured inverse scattering length on bubbles decreases linearly with increasing depth in the volume of ice investigated.

Regenerating muscle fibers in 25 human muscle biopsies, obtained from patients with a variety of neuromuscular diseases, manifested increased mRNA for the beta-amyloid precursor protein (beta APP) that contains the Kunitz-type protease inhibitor (KPI) motif, whereas adult human muscle fibers were negative in their vast non-extrajunctional region. Aneurally cultured normal human muscle fibers also expressed strong KPI-beta APP mRNA signal, which became significantly down-regulated during muscle differentiation. Our study demonstrates that in human muscle KPI-beta APP mRNA is developmentally regulated, and it suggests that beta APP may play a role in human muscle development.

Although our knowledge of the cellular components of the cortex is accumulating rapidly, we are still largely ignorant about how distributed neuronal activity can be integrated to contribute to unified perception and behaviour. In the visual system, it is still unresolved how responses of feature-detecting neurons can be bound into representations of perceptual objects. Recent crosscorrelation studies show that visual cortical neurons synchronize their responses depending on how coherent features are in the visual field. These results support the hypothesis that temporal correlation of neuronal discharges may serve to bind distributed neuronal activity into unique representations. Furthermore, these studies indicate that neuronal responses with an oscillatory temporal structure may be particularly advantageous as carrier signals for such a temporal coding mechanism. Based on these recent findings, it is suggested here that binding of neuronal activity by a temporal code may provide a solution to the problem of integration in distributed neuronal networks.

The profile of a family of subsets of an n -element set is a vector [fnof] = ([fnof] 0 ,…,[fnof] n ), where [fnof] k denotes the number of k -element sets in the family. Using a new method the extreme points of the convex hull of the profiles of all complementfree Sperner families over an n -element set are determined.