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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.

Correlations in spontaneous brain activity provide powerful access to large-scale organizational principles of the CNS. However, making inferences about cognitive processes requires a detailed understanding of the link between these couplings and the structural integrity of the CNS. We studied the impact of multiple sclerosis, which leads to the severe disintegration of the central white matter, on functional connectivity patterns in spontaneous cortical activity. Using a data driven approach based on the strength of a salient pattern of cognitive pathology, we identified distinct networks that exhibit increases in functional connectivity despite the presence of strong and diffuse reductions of the central white-matter integrity. The default mode network emerged as a core target of these connectivity modulations, showing enhanced functional coupling in bilateral inferior parietal cortex, posterior cingulate, and medial prefrontal cortex. These findings imply a complex and diverging relation of anatomical and functional connectivity in early multiple sclerosis and, thus, add an important observation for understanding how cognitive abilities and CNS integrity may be reflected in the intrinsic covariance of functional signals.

A critical parameter of brain-computer interfaces (BCIs) is the number of dimensions a user can control independently. One way to increment this number without increasing the mental effort required to operate the system is to stimulate several sensory modalities simultaneously, and to distinguish brain activity patterns when the user focuses attention to different elements of this multisensory input. In this article we show how shifting attention between simultaneously presented tactile and visual stimuli affects the electrical brain activity of human subjects, and that this signal can be used to augment the control information from the two uni-modal BCI subsystems.

When visual sensory information is restricted, we often rely on haptic and auditory information to recognize objects. Here we examined how haptic exploration of familiar objects affects neural processing of subsequently presented sounds of objects. Recent studies indicated that oscillatory responses, in particular in the gamma band (30–100 Hz), reflect cross-modal processing, but it is not clear which cortical networks are involved. In this high-density EEG study, we measured gamma-band activity (GBA) in humans performing a haptic-to-auditory priming paradigm. Haptic stimuli served as primes, and sounds of objects as targets. Haptic and auditory stimuli were either semantically congruent or incongruent, and participants were asked to categorize the objects represented by the sounds. Response times were shorter for semantically congruent compared with semantically incongruent inputs. This haptic-to-auditory priming effect was associated with enhanced total power GBA (250–350 ms) for semantically congruent inputs and additional effects of semantic congruency on evoked GBA (50–100 ms). Source reconstruction of total GBA using linear beamforming revealed effects of semantic congruency in the left lateral temporal lobe, possibly reflecting matching of information across modalities. For semantically incongruent inputs, total GBA was enhanced in middle frontal cortices, possibly indicating the processing or detection of conflicting information. Our findings demonstrate that semantic priming by haptic object exploration affects processing of auditory inputs in the lateral temporal lobe and suggest an important role of oscillatory activity for multisensory processing.

The striatum integrates sensory information to enable action selection and behavioural reinforcement. In the rat, a large topographical projection from the rat barrel cortex to widely distributed areas of the striatum is assumed to be an important structural component supporting these processes. The striatal sensory response is, however, not comprehensively understood at a network level. We used a 10-Hz, 100-ms air puff, allowing undamped movement of multiple whiskers, to look at functional connectivity in contralateral cortex and striatum in response to sensory stimulation. Simultaneous recordings of cortical and striatal local field potentials (LFPs) were made under isoflurane anaesthesia in 15 male Brown Norway rats. Four electrodes were placed in the barrel cortex while the dorsolateral striatum was mapped with a 500-μm resolution, resulting in a maximum of 315 recording positions per animal. Significant event-related responses were unevenly distributed throughout the striatum in 34.8% of positions recorded within this area. Only 10.3% of recorded positions displayed significant total power increases in the LFPs during the stimulation period at the stimulus frequency. This suggests that the responses seen in the LFPs are due to phase rearrangement rather than an amplitude increase in the signal. Analysis of corticostriatal imaginary coherence revealed stimulus-induced changes in the functional connectivity of 12% of corticostriatal pairs, the sensory response of sparsely distributed neuronal ensembles within the dorsolateral striatum is reflected in the phase relationship between the cortical and striatal local fields.

“Don’t look and it won’t hurt” is common ad­vice heard before receiving an injection, but is there any truth in this statement? Pain pro­cessing can be separated into two major components: a sensory-discriminative com­ponent, which reflects the location and inten­sity of a painful event, and an affective-mo­tivational component that reflects the un­pleasantness of pain. The differentiation be­tween these components and the effects of additional sensory inputs on them becomes apparent if you watch a needle penetrating your skin: On the one hand, it may be some­what reassuring to know precisely when and where to expect the pinprick, on the other hand, you eye-witness damage inflicted on your body, which can increase personal dis­tress. Here we review recent studies, which demonstrate that a host of variables such as onset timing, spatial alignment, semantic meaning, and attention differentially affect how visual inputs influence pain processing. These studies also indicate that there is some truth in the opening statement.

Zusammenfassung „Schau‘ nicht hin, dann tut‘s gar nicht weh“ ist ein Rat, den man oft zu hören bekommt, wenn eine Impfung bevorsteht. Aber ist diese Empfehlung überhaupt gerechtfertigt? Schmerzverarbeitung kann in zwei Hauptkomponenten eingeteilt werden: eine sen­sorisch-diskriminative Komponente, die Ort und Intensität eines Schmerzereignisses widerspiegelt, und eine affektiv-motivationale Komponente, welche die Unangenehmheit dieses Ereignisses widerspiegelt. Die Differenzierung dieser Komponenten und der Einfluss zusätzlicher sensorischer Reize werden deutlich, wenn Sie sich vorstellen, eine Nadel in Ihre Haut eindringen zu sehen: Einerseits mag es beruhigend sein zu wissen, wann und wo der Einstich zu erwarten ist, andererseits kann es sehr unangenehm sein, Zeuge der Schädigung des eigenen Körpers zu werden. In diesem Artikel werden wir aktuelle Studien vorstellen, die zeigen, dass eine ganze Reihe von Einflussfaktoren, wie zeitliche und räumliche Anordnung, semantischer Gehalt und Aufmerksamkeit, die Effekte visueller Reize auf die Schmerzverarbeitung modulieren. Diese Studien weisen darauf hin, dass man tatsächlich gut beraten ist, nicht hinzuschauen.

Central processing of acoustic signals is assumed to take place ina stereotypical spatial and temporal pattern involving differentfields of auditory cortex. So far, cortical propagating wavesrepresenting such patterns have mainly been demonstrated byoptical imaging, repeatedly in the visual and somatosensory cortex.In this study, the surface of rat auditory cortex was mapped byrecording local field potentials (LFPs) in response to a broadbandacoustic stimulus. From the peak amplitudes of LFPs, corticalactivation maps were constructed over 4 cortical auditory fields.Whereas response onset had same latencies across primary auditoryfield (A1), anterior auditory field (AAF), and ventral auditory field andlonger latencies in posterior auditory field, activation maps revealeda reproducible wavelike pattern of activity propagating for ~45 mspoststimulus through all cortical fields. The movement observedstarted with 2 waves within the primary auditory fields A1 and AAFmoving from ventral to dorsal followed by a motion from rostral tocaudal, passing continuously through higher-order fields. The patternof propagating waves was well reproducible and showed only minorchanges if different anesthetics were used. The results question theclassical ‘‘hierarchical’’ model of cortical areas and demonstrate thatthe different fields process incoming information as a functional unit.Keywords: anesthesia, cortical hierarchy, cortical organization,spatiotemporal pattern, traveling waveIntroductionThe brain represents features of sensory stimuli by the locationof maximal excitation and by temporal features of neuronalresponses. Provided that these 2 organizational principles act incoordinated fashion, they should generate a complex spatio-temporalpatternofevokedactivity.Indeed,propagatingcorticalwaveshavebeenreportedinthevisual(Prechtletal.1997,2000;Senseman and Robbins 1999; Sharon and Grinvald 2002; Rolandet al. 2006; Benucci et al. 2007; Xu et al. 2007), somatosensory(Derdikman et al. 2003; Petersen et al. 2003), and motor cortex(Rubinoetal.2006)aswellasintheolfactorybulb(Delaneyetal.1994). Propagating waves result when groups of neuronssequentially depolarize and hyperpolarize with small delays;the activity ‘‘travels’’ through the cortex according to the orderandthedegreeofactivationofareas.Thevastmajorityofreportson cortical propagating waves applied optical imaging methods(Delaney et al. 1994; Prechtl et al. 1997; Sharon and Grinvald2002; Derdikman et al. 2003; Petersen et al. 2003; Roland et al.2006; Benucci et al. 2007; Xu et al. 2007).In the auditory system, evoked propagating waves in thetimescale of hundreds of milliseconds have been described andshown to propagate mainly within the isofrequency stripe infield primary auditory field (A1) (Bakin et al. 1996; Hess andScheich 1996; Tsytsarev and Tanaka 2002; Tsytsarev et al.2004). Using voltage-sensitive dyes, a cortical wave in thetimescale of dozens of milliseconds was observed, againpropagating within the isofrequency stripe (Song et al. 2006).This spread of activity has an anatomical correlate as thalamicafferents spread within the isofrequency stripe in a patchypattern (Velenovsky et al. 2003; McMullen et al. 2005). On theother hand, both thalamocortical as well as corticocorticalprojections involve a significant extent of cortical tissueorthogonal to the isofrequency stripe (Lee and Winer 2008a,2008b). Most likely, the propagation within the isofrequencyband has been the consequence of pure tone stimulation usedin previous studies, selected in the attempt to demonstratecochleotopic cortical organization of the cortex and by that toverify the usefulness of optical imaging methods.Optical imaging methods, especially intrinsic optical signals,have a high spatial resolution but hold the disadvantage ofbeing insensitive to rapid changes in the temporal domain(Nelkenetal.2008;fordependenceonwavelength,seeTsytsarevet al. 2008), thus providing temporally smoothed patterns of fastcortical activity. Voltage-sensitive dyes, although essentially toxicfor neurons, allow determining faster changes of neuronalactivity (Song et al. 2006; Tsytsarev et al. 2008). Differences intiming in the range of few milliseconds appear cardinal incortical representation of the sensory world (Goure´vitch andEggermont 2007; Wei et al. 2008) and possibly in differentiatingauditory objects (Nelken 2004). Consequently, direct electro-physiological investigations of propagating waves are required toinvestigate the true temporal scale over which they occur. Incochlear-implanted cats, a first electrophysiological study indeedobserved a complex pattern of waves and ‘‘reflection’’ waves infields A1 and anterior auditory field (AAF) evoked by electricalcochlear stimulation (Kral et al. 2009).The present study demonstrates that evoked propagatingwaves can be observed also with acoustic stimuli, that theycover the whole auditory cortex, and that they travel in 2directions: within A1 first dorsally, then also caudally andventrally, and within AAF first dorsally, then ventrorostrally.Both activation fronts (from A1 and AAF) unify in passingthrough ventral auditory field (VAF) and end in posteriorauditory field (PAF). To minimize a possible contamination ofthe wave by the anesthetics, 3 different anesthetic conditionswith differently acting anesthetics were compared: 2 volatileanesthetics (isoflurane with and without nitrous oxide) and 1nonvolatile anesthetic agent (ketamine). The study demon-strates that despite specific effects of the different anesthetics,cortical propagating waves constitute a stable phenomenon.The propagating waves demonstrated in this investigationfurther allow drawing conclusions about the hierarchical orderof the cortical sensory areas in rat auditory cortex.

In this review, we consider the potential functional role of beta-band oscillations, which at present is not yet well understood. We discuss evidence from recent studies on top-down mechanisms involved in cognitive processing, on the motor system and on the pathophysiology of movement disorders that suggest a unifying hypothesis: beta-band activity seems related to the maintenance of the current sensorimotor or cognitive state. We hypothesize that beta oscillations and/or coupling in the beta-band are expressed more strongly if the maintenance of the status quo is intended or predicted, than if a change is expected. Moreover, we suggest that pathological enhancement of beta-band activity is likely to result in an abnormal persistence of the status quo and a deterioration of flexible behavioural and cognitive control.

In real-world situations, the integration of sensory information in working memory (WM) is an important mechanism for the recognition of objects. Studies in single sensory modalities show that object recognition is facilitated if bottom-up inputs match a template held in WM, and that this effect may be linked to enhanced synchronization of neurons in the gamma-band (>30 Hz). Natural objects, however, frequently provide inputs to multiple sensory modalities. In this EEG study, we examined the integration of semantically matching or non-matching visual and auditory inputs using a delayed visual-to-auditory object-matching paradigm. In the event-related potentials (ERPs) triggered by auditory inputs, effects of semantic matching were observed after 120-170 ms at frontal and posterior regions, indicating WM-specific processing across modalities, and after 250-400 ms over medial-central regions, possibly reflecting the contextual integration of sensory inputs. Additionally, total gamma-band activity (GBA) with medial-central topography after 120-180 ms was larger for matching compared to non-matching trials. This demonstrates that multisensory matching in WM is reflected by GBA and that dynamic coupling of neural populations in this frequency range might be a crucial mechanism for integrative multisensory processes.

The striatum is the key site for cortical input to the basal ganglia. Cortical input to striatal microcircuits has been previously studied only in the context of one or two types of neurons. Here, we provide the first description of four putative types of striatal neurons (medium spiny, fast spiking, tonically active, and low-threshold spiking) in a single data set by separating extracellular recordings of sorted single spikes recorded under halothane anesthesia using waveform and burst parameters. Under halothane, the electrocorticograms and striatal local field potential displayed spontaneous oscillations at both low (2–9 Hz) and high (35–80 Hz) frequencies. Putative fast spiking interneurons were significantly more likely to phase lock to high-frequency cortical oscillations and displayed significant cross-correlations in this frequency range. These findings suggest that, as in neocortex and hippocampus, the coordinated activity of fast spiking interneurons may specifically be involved in mediating oscillatory synchronization in the striatum.

Claudia Domnick1, Michael Hauck1,2,3, Kenneth L Casey3, Andreas K Engel1, Jürgen Lorenz1,3,41Department of Neurophysiology and Pathophysiology; 2Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; 3Department of Neurology, University of Michigan, Ann Arbor, MI, USA; 4Faculty of Life Sciences, Hamburg University of Applied Sciences, Hamburg, GermanyAbstract: Nociceptive input reaches the brain via two different types of nerve fibers, moderately fast A-delta and slowly conducting C-fibers, respectively. To explore their distinct roles in normal and inflammatory pain we used laser stimulation of normal and capsaicin treated skin at proximal and distal arm sites in combination with time frequency transformation of electroencephalography (EEG) data. Comparison of phase-locked (evoked) and non-phase-locked (total) EEG to laser stimuli revealed three significant pain-related oscillatory responses. First, an evoked response in the delta-theta band, mediated by A-fibers, was reduced by topical capsaicin treatment. Second, a decrease of total power in the alpha-to-gamma band reflected both an A- and C-nociceptor-mediated response with only the latter being reduced by capsaicin treatment. Finally, an enhancement of total power in the upper beta band was mediated exclusively by C-nociceptors and appeared strongly augmented by capsaicin treatment. These findings suggest that phase-locking of brain activity to stimulus onset is a critical feature of A-delta nociceptive input, allowing rapid orientation to salient and potentially threatening events. In contrast, the subsequent C-nociceptive input exhibits clearly less phase coupling to the stimulus. It may primarily signal the tissue status allowing more long-term behavioral adaptations during ongoing inflammatory events thataccompany tissue damage.Keywords: C-fibers, oscillations, EEG, laser, capsaicin, inflammatory pain

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.

Rats perform texture discrimination during tactile exploration with their whiskers with high spatial and temporal precision. Although the peripheral mechanoreceptors provide tactile information with exquisite temporal resolution, physiological studies have suggested that this information might be lost at the cortical level. To address this discrepancy, multiunit and single-unit recordings were performed in the barrel cortex of isoflurane-anesthetized rats using continuous sinusoidal vibration of single whiskers at 15–700 Hz. In multiunit recordings, sustained phase-locked responses occurred up to vibration frequencies of 700 Hz, and 1:1 stimulus locking was observed up to 320 Hz. Wide-band responses of multiunits showed frequency encoding between 20 and 320 Hz. The discharge rates were not different for stimuli in the low- and high-frequency ranges, but they were significantly lower for non-phase-locked responses to high-frequency vibration. Response adaptation was present in only 25% of the cases, whereas in the majority of cases, entrainment to the vibratory frequency remained constant or even increased with stimulus duration. Increased entrainment to high-frequency stimulation was accompanied by the emergence of induced activity in the gamma-band range. Analysis of single-unit activity revealed that phase locking to vibratory stimuli was more precise than that observed for the multiunit responses. The results show that whisker vibrations at frequencies above 100 Hz are faithfully encoded by sustained phase-locked responses of cortical neurons under isoflurane anesthesia. It is conceivable that the awake animal makes use of the tactile signals at even much higher frequencies, which can be provided by the peripheral mechanoreceptors during texture discrimination.

The question of how vision and audition interact in natural object identification is currently a matter of debate. We developed a large set of auditory and visual stimuli representing natural objects in order to facilitate research in the field of multisensory processing. Normative data was obtained for 270 brief environmental sounds and 320 visual object stimuli. Each stimulus was named, categorized, and rated with regard to familiarity and emotional valence by N = 56 participants (Study 1). This multimodal stimulus set was employed in two subsequent crossmodal priming experiments that used semantically congruent and incongruent stimulus pairs in a S1-S2 paradigm. Task-relevant targets were either auditory (Study 2) or visual stimuli (Study 3). The behavioral data of both experiments expressed a crossmodal priming effect with shorter reaction times for congruent as compared to incongruent stimulus pairs. The observed facilitation effect suggests that object identification in one modality is influenced by input from another modality. This result implicates that congruent visual and auditory stimulus pairs were perceived as the same object and demonstrates a first validation of the multimodal stimulus set.

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Dysfunctions of the human mirror neuron system have been postulated to underlie some deficits in autism spectrum disorders including poor imitative performance and impaired social skills. Using three reaction time experiments addressing mirror neuron system functions under simple and complex conditions, we examined 20 adult autism spectrum disorder participants and 20 healthy controls matched for age, gender and education. Participants performed simple finger-lifting movements in response to (1) biological finger and non-biological dot movement stimuli, (2) acoustic stimuli and (3) combined visual-acoustic stimuli with different contextual (compatible/incompatible) and temporal (simultaneous/asynchronous) relation. Mixed model analyses revealed slower reaction times in autism spectrum disorder. Both groups responded faster to biological compared to non-biological stimuli (Experiment 1) implying intact processing advantage for biological stimuli in autism spectrum disorder. In Experiment 3, both groups had similar ‘interference effects’ when stimuli were presented simultaneously. However, autism spectrum disorder participants had abnormally slow responses particularly when incompatible stimuli were presented consecutively. Our results suggest imitative control deficits rather than global imitative system impairments.

Contains fulltext : 34457.pdf (Publisher’s version ) (Closed access) Brain processing depends on the interactions between neuronal groups. Those interactions are governed by the pattern of anatomical connections and by yet unknown mechanisms that modulate the effective strength of a given connection. We found that the mutual influence among neuronal groups depends on the phase relation between rhythmic activities within the groups. Phase relations supporting interactions between the groups preceded those interactions by a few milliseconds, consistent with a mechanistic role. These effects were specific in time, frequency, and space, and we therefore propose that the pattern of synchronization flexibly determines the pattern of neuronal interactions. 4 p.

Background To date, the anesthesia-induced blockade of nociceptive inputs is insufficiently reflected by commercially available electroencephalographic depth-of-anesthesia monitors. The aim of the current study was to evaluate the potential of somatosensory (SSEP) and intracutaneous pain evoked (iSEP) potentials during remifentanil and propofol anesthesia as electroencephalographic indicators of the nociceptive blockade. Methods Ten healthy men were investigated in a double-blind crossover design during three sessions with remifentanil, propofol, and placebo administration. All dosages were increased in a step-by-step mode. SSEP and iSEP recordings were performed followed by subjective pain ratings and measurement of level of sedation (modified Observer's Assessment of Alertness and Sedation Scale). Changes from baseline in evoked potential components, pain ratings, and sedation scale were assessed by Bonferroni-Holms-corrected Wilcoxon tests. Results Pain ratings were significantly reduced by remifentanil. Sedation scale was significantly reduced by propofol. Early SSEP components were not affected by medication. The amplitudes of the long latency SSEP components increased significantly with remifentanil, decreased with propofol, and did not change with placebo. The amplitudes of long latency components of the iSEP decreased significantly with both remifentanil and propofol and did not change with placebo. Conclusion Long latency components of the SSEP are differently affected by remifentanil and propofol administration. Further studies are needed to clarify whether they can serve as a specific indicator of the nociceptive blockade during anesthesia.

Autism spectrum disorders (ASD) have been associated with altered neural oscillations, especially fast oscillatory activity in the gamma frequency range, suggesting fundamentally disturbed temporal coordination of activity during information processing. A detailed review of available cortical oscillation studies in ASD does not convey a clear-cut picture with respect to dysfunctional oscillation patterns in the gamma or other frequency ranges. Recent evidence suggests that instead of a general failure to activate or synchronize the cortex, there is greater intra-participant variability across behavioral, fMRI and EEG responses in ASD. Intra-individual fluctuations from one trial to another have been largely ignored in task-related neural oscillation studies of ASD, which instead have focused on mean changes in power. We highlight new avenues for the analysis of cortical oscillation patterns in ASD which are sensitive to trial-to-trial variability within the participant, in order to validate the significance of increased response variability as possible endophenotype of the disorder.

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Correlation of ongoing neural dynamics reveals the various carrier frequencies of cortico-tectal functional interaction., In the absence of sensory stimulation or motor output, the brain exhibits complex spatiotemporal patterns of intrinsically generated neural activity. Analysis of ongoing brain dynamics has identified the prevailing modes of cortico-cortical interaction; however, little is known about how such patterns of intrinsically generated activity are correlated between cortical and subcortical brain areas. We investigate the correlation structure of ongoing cortical and superior colliculus (SC) activity across multiple spatial and temporal scales. Ongoing cortico-tectal interaction was characterized by correlated fluctuations in the amplitude of delta, spindle, low gamma, and high-frequency oscillations (>100 Hz). Of these identified coupling modes, topographical patterns of high-frequency coupling were the most consistent with patterns of anatomical connectivity, reflecting synchronized spiking within cortico-tectal networks. Cortico-tectal coupling at high frequencies was temporally parcellated by the phase of slow cortical oscillations and was strongest for SC-cortex channel pairs that displayed overlapping visual spatial receptive fields. Despite displaying a high degree of spatial specificity, cortico-tectal coupling in lower-frequency bands did not match patterns of cortex-to-SC anatomical connectivity. Collectively, our findings demonstrate that neural activity is spontaneously coupled between cortex and SC, with high- and low-frequency modes of coupling reflecting direct and indirect cortico-tectal interactions, respectively.

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 reduced alpha power through enhanced AECs. These results provide causal evidence for the functional role of coupled alpha and gamma oscillations for visual processing.

Goal-directed behavior requires the continuous monitoring and dynamic adjustment of ongoing actions. Here, we report a direct coupling between the event-related electroencephalogram (EEG), functional magnetic resonance imaging (fMRI), and behavioral measures of performance monitoring in humans. By applying independent component analysis to EEG signals recorded simultaneously with fMRI, we found the single-trial error-related negativity of the EEG to be systematically related to behavior in the subsequent trial, thereby reflecting immediate behavioral adjustments of a cognitive performance monitoring system. Moreover, this trial-by-trial EEG measure of performance monitoring predicted the fMRI activity in the rostral cingulate zone, a brain region thought to play a key role in processing of response errors. We conclude that investigations of the dynamic coupling between EEG and fMRI provide a powerful approach for the study of higher order brain functions.

Evidence is available that oscillatory activity in the gamma frequency range (>30 Hz) might be related to the attentional selection of target items. Rapid serial visual presentation (RSVP) paradigms are instrumental in addressing cognitive functions such as visual attention, and they are increasingly combined with the measurement of electrical brain activity. In the present study, gamma-band responses for target and standard stimuli were investigated in an RSVP oddball paradigm. In a first study, stimuli were presented at a frequency of 10 Hz, the stimulus sequence consisted of rare colored letters (targets) and frequent black letters (standards). In addition, stimulus size was varied across experimental blocks. Significant target modulations were observed for the P3 ERP and induced (i.e., not phase-locked) gamma-band responses. Besides this late activation, no further gamma-band responses were observed. A second study aimed at replicating these findings by employing a reduced stimulus presentation rate of 7.1 Hz. Again, besides the P3 ERP a late increase in induced gamma-band activity was observed. However, as compared to Study 1, this induced response was less pronounced. The induced gamma-band response observed in the present studies might reflect utilization of information derived from previous processing steps for behavioral performance or memory storage as suggested in the 'match-and-utilization-model' of gamma activity.

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.

Zusammenfassung Operative Eingriffe in den Basalganglien zur Therapie schwerer Bewegungsstörungen werden bereits seit über 50 Jahren durchgeführt. Seit der Ablösung der klassischen läsionellen Operationstechnik durch die chronische Tiefenhirnstimulation haben stereotaktische Operationen in den letzten Jahren als Behandlungsalternative wieder an Bedeutung gewonnen. Der Operationserfolg hängt dabei von einer präzisen Platzierung der zur Stimulation verwendeten Elektrode am Zielort ab. Für die millimetergenaue Orientierung in den Tiefenstrukturen des Gehirns zeichnet man Nervenzellsignale mit Hilfe von Mikroelektroden auf. Diese Technik ermöglicht die Darstellung der subkortikalen Kerngrenzen, die Abgrenzung funktioneller Kernregionen sowie die Bestimmung pathologischer neuronaler Aktivitätsmuster, und ist damit im klinischen Kontext von grosser Bedeutung. Intraoperative Mikroelektrodenableitungen ermöglichen aber auch einzigartige Einblicke in die neuronalen Vorgänge in Tiefenstrukturen des menschlichen Gehirns. Neben einem Überblick über den praktischen Einsatz von Mikroelektroden in den Basalganglien des Menschen soll skizziert werden, wie mit dieser Technik aktuelle, aus der tierexperimentellen Physiologie herrührende Hypothesen getestet werden können.

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.

Although non-invasive methods such as functional magnetic resonance imaging, electroencephalograms and magnetoencephalograms provide most of the current data about the human brain, their resolution is insufficient to show physiological processes at the cellular level. Clinical approaches sometimes allow invasive recordings to be taken from the human brain, mainly in patients with epilepsy or with movement disorders, and such recordings can sample neural activity at spatial scales ranging from single cells to distributed cell assemblies. In addition to their clinical relevance, these recordings can provide unique insights into brain functions such as movement control, perception, memory, language and even consciousness.

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.

Background: High frequency oscillations in the gamma range are known to be involved in early stages of auditory information processing in terms of synchronization of brain regions, e.g., in cognitive functions. It has been shown using EEG source localisation, as well as simultaneously recorded EEG-fMRI, that the auditory evoked gamma-band response (aeGBR) is modulated by attention. In addition to auditory cortex activity a dorsal anterior cingulate cortex (dACC) generator could be involved. In the present study we investigated aeGBR magnetic fields using magnetoencephalography (MEG). We aimed to localize the aeGBR sources and its connectivity features in relation to mental effort. Methods: We investigated the aeGBR magnetic fields in 13 healthy participants using a 275-channel CTF-MEG system. The experimental paradigms were two auditory choice reaction tasks with different difficulties and demands for mental effort. We performed source localization with eLORETA and calculated the aeGBR lagged phase synchronization between bilateral auditory cortices and frontal midline structures. Results: The eLORETA analysis revealed sources of the aeGBR within bilateral auditory cortices and in frontal midline structures of the brain including the dACC. Compared to the control condition the dACC source activity was found to be significantly stronger during the performance of the cognitively demanding task. Moreover, this task involved a significantly stronger functional connectivity between auditory cortices and dACC. Conclusion: In accordance with previous EEG and EEG-fMRI investigations, our study confirms an aeGBR generator in the dACC by means of MEG and suggests its involvement in the effortful processing of auditory stimuli.

During the last two decades ferrets (Mustela putorius) have been established as a highly efficient animal model in different fields in neuroscience. Here we asked whether ferrets integrate sensory information according to the same principles established for other species. Since only few methods and protocols are available for behaving ferrets we developed a head-free, body-restrained approach allowing a standardized stimulation position and the utilization of the ferret?s natural response behavior. We established a behavioral paradigm to test audiovisual integration in the ferret. Animals had to detect a brief auditory and/or visual stimulus presented either left or right from their midline. We first determined detection thresholds for auditory amplitude and visual contrast. In a second step, we combined both modalities and compared psychometric fits and the reaction times between all conditions. We employed Maximum Likelihood Estimation (MLE) to model bimodal psychometric curves and to investigate whether ferrets integrate modalities in an optimal manner. Furthermore, to test for a redundant signal effect we pooled the reaction times of all animals to calculate a race model. We observed that bimodal detection thresholds were reduced and reaction times were faster in the bimodal compared to unimodal conditions. The race model and MLE modeling showed that ferrets integrate modalities in a statistically optimal fashion. Taken together, the data indicate that principles of multisensory integration previously demonstrated in other species also apply to crossmodal processing in the ferret.

The integration of visual details into a holistic percept is essential for object recognition. This integration has been reported as a key deficit in patients with autism spectrum disorders (ASDs). The weak central coherence account posits an altered disposition to integrate features into a coherent whole in ASD. Here, we test the hypothesis that such weak perceptual coherence may be reflected in weak neural coherence across different cortical sites. We recorded magnetoencephalography from 20 adult human participants with ASD and 20 matched controls, who performed a slit-viewing paradigm, in which objects gradually passed behind a vertical or horizontal slit so that only fragments of the object were visible at any given moment. Object recognition thus required perceptual integration over time and, in case of the horizontal slit, also across visual hemifields. ASD participants were selectively impaired in the horizontal slit condition, indicating specific difficulties in long-range synchronization between the hemispheres. Specifically, the ASD group failed to show condition-related enhancement of imaginary coherence between the posterior superior temporal sulci in both hemispheres during horizontal slit-viewing in contrast to controls. Moreover, local synchronization reflected in occipitocerebellar beta-band power was selectively reduced for horizontal compared with vertical slit-viewing in ASD. Furthermore, we found disturbed connectivity between right posterior superior temporal sulcus and left cerebellum. Together, our results suggest that perceptual integration deficits co-occur with specific patterns of abnormal global and local synchronization in ASD.SIGNIFICANCE STATEMENTThe weak central coherence account proposes a tendency of individuals with autism spectrum disorders (ASDs) to focus on details at the cost of an integrated coherent whole. Here, we provide evidence, at the behavioral and the neural level, that visual integration in object recognition is impaired in ASD, when details had to be integrated across both visual hemifields. We found enhanced interhemispheric gamma-band coherence in typically developed participants when communication between cortical hemispheres was required by the task. Importantly, participants with ASD failed to show this enhanced coherence between bilateral posterior superior temporal sulci. The findings suggest that visual integration is disturbed at the local and global synchronization scale, which might bear implications for object recognition in ASD.

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.

Contains fulltext : 165221.pdf (Publisher’s version ) (Open Access) Spike and local field potential activity were recorded simultaneously from multiple sites in primary visual cortex of strabismic cats, while monocular stimulation alternated with dichoptic stimulation, inducing interocular rivalry. During interocular rivalry, there is competition between the two nonfusible stimuli presented to the two eyes, and only one stimulus is selected at any time. We biased this competition in three different ways: (1) we exploited the condition that in strabismic cats there is often one dominant eye that is selected for most of the time. (2) We presented the two stimuli with a temporal offset, which biases competition in favor of the newly appearing stimulus. (3) We presented the two stimuli with highly different contrasts, which biases competition in favor of the stimulus with higher contrast. Whenever competition was biased in favor of the stimulus activating the recorded neurons, gamma-frequency synchronization of the respective responses was enhanced, and vice versa. Firing rates showed some differences between stimulation conditions. However, when present, these changes were inversely related to a competitive advantage of the respective stimulus. We hypothesize that enhanced gamma-frequency synchronization in primary visual cortex is a correlate of stimulus selection. Synchronization is likely to be translated into firing rate changes at later processing stages.

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).

Interhemispheric auditory connectivity via the corpus callosum has been demonstrated to be important for normal speech processing. According to the callosal relay model, directed information flow from the right to the left auditory cortex has been suggested, but this has not yet been proven. For this purpose, 33 healthy participants were investigated with 64-channel EEG while performing the dichotic listening task in which two different consonant-vowel syllables were presented simultaneously to the left (LE) and right ear (RE). eLORETA source estimation was used to investigate the functional (lagged phase synchronization/LPS) and effective (isolated effective coherence/ICoh) connectivity between right and left primary (PAC) and secondary auditory cortices (SAC) in the gamma-band (30-100 Hz) during right and left ear reports. The major finding was a significantly increased effective connectivity in the gamma-band from the right to the left SAC during conscious perception of LE stimuli. In addition, effective and functional connectivity was significantly enhanced during LE as compared to RE reports. These findings give novel insight into transcallosal information transfer during auditory perception by showing that LE performance requires causal interhemispheric inputs from the right to the left auditory cortices, and that this interaction is mediated by synchronized gamma-band oscillations.

Touch can be localized either on the skin in anatomical coordinates, or, after integration with posture, in external space. Sighted individuals are thought to encode touch in both coordinate systems concurrently, whereas congenitally blind individuals exhibit a strong bias for using anatomical coordinates. We investigated the neural correlates of this differential dominance in the use of anatomical and external reference frames by assessing oscillatory brain activity during a tactile spatial attention task. The EEG was recorded while sighted and congenitally blind adults received tactile stimulation to uncrossed and crossed hands while detecting rare tactile targets at one cued hand only. In the sighted group, oscillatory alpha-band activity (8-12Hz) in the cue-target interval was reduced contralaterally and enhanced ipsilaterally with uncrossed hands. Hand crossing attenuated the degree of posterior parietal alpha-band lateralization, indicating that attention deployment was affected by external spatial coordinates. Beamforming suggested that this posture effect originated in the posterior parietal cortex. In contrast, cue-related lateralization of central alpha-band as well as of beta-band activity (16-24Hz) were unaffected by hand crossing, suggesting that these oscillations exclusively encode anatomical coordinates. In the blind group, central alpha-band activity was lateralized, but did not change across postures. The pattern of beta-band activity was indistinguishable between groups. Because the neural mechanisms for posterior alpha-band generation seem to be linked to developmental vision, we speculate that the lack of this neural mechanism in blind individuals is related to their preferred use of anatomical over external spatial codes in sensory processing.

The integration of visual and auditory spatial information is important for building an accurate perception of the external world, but the fundamental mechanisms governing such audiovisual interaction have only partially been resolved. The earliest interface between auditory and visual processing pathways is in the midbrain, where the superior (SC) and inferior colliculi (IC) are reciprocally connected in an audiovisual loop. Here, we investigate the mechanisms of audiovisual interaction in the midbrain by recording neural signals from the SC and IC simultaneously in anesthetized ferrets. Visual stimuli reliably produced band-limited phase locking of IC local field potentials (LFPs) in two distinct frequency bands: 6-10 and 15-30 Hz. These visual LFP responses co-localized with robust auditory responses that were characteristic of the IC. Imaginary coherence analysis confirmed that visual responses in the IC were not volume-conducted signals from the neighboring SC. Visual responses in the IC occurred later than retinally driven superficial SC layers and earlier than deep SC layers that receive indirect visual inputs, suggesting that retinal inputs do not drive visually evoked responses in the IC. In addition, SC and IC recording sites with overlapping visual spatial receptive fields displayed stronger functional connectivity than sites with separate receptive fields, indicating that visual spatial maps are aligned across both midbrain structures. Reciprocal coupling between the IC and SC therefore probably serves the dynamic integration of visual and auditory representations of space.

Background Disturbed functional connectivity is assumed to underlie neurocognitive deficits in patients with schizophrenia. As neurocognitive deficits are already present in the high-risk state, identification of the neural networks involved in this core feature of schizophrenia is essential to our understanding of the disorder. Resting-state studies enable such investigations, while at the same time avoiding the known confounder of impaired task performance in patients. The aim of the present study was to investigate EEG resting-state connectivity in high-risk individuals (HR) compared to first episode patients with schizophrenia (SZ) and to healthy controls (HC), and its association with cognitive deficits. Methods 64-channel resting-state EEG recordings (eyes closed) were obtained for 28 HR, 19 stable SZ, and 23 HC, matched for age, education, and parental education. The imaginary coherence-based multivariate interaction measure (MIM) was used as a measure of connectivity across 80 cortical regions and six frequency bands. Mean connectivity at each region was compared across groups using the non-parametric randomization approach. Additionally, the network-based statistic was applied to identify affected networks in patients. Results SZ displayed increased theta-band resting-state MIM connectivity across midline, sensorimotor, orbitofrontal regions and the left temporoparietal junction. HR displayed intermediate theta-band connectivity patterns that did not differ from either SZ or HC. Mean theta-band connectivity within the above network partially mediated verbal memory deficits in SZ and HR. Conclusions Aberrant theta-band connectivity may represent a trait characteristic of schizophrenia associated with neurocognitive deficits. As such, it might constitute a promising target for novel treatment applications.

Rats probe objects with their whiskers and make decisions about sizes, shapes, textures and distances within a few tens of milliseconds. This perceptual analysis requires the processing of tactile high-frequency object components reflecting surface roughness. We have shown that neurons in the barrel cortex of rats encode high-frequency sinusoidal vibrations of whiskers for sustained periods when presented with constant amplitudes and frequencies. In a natural situation, however, stimulus parameters change rapidly when whiskers are brushing across objects. In this study, we therefore analysed cortical responses to vibratory movements of single whiskers with rapidly changing amplitudes and frequencies. The results show that different neural codes are employed for a processing of stimulus parameters. The frequency of whisker vibration is encoded by the temporal pattern of spike discharges, i.e., the phase-locked responses of barrel cortex neurons. In addition, oscillatory gamma band activity was induced during high-frequency stimulation. The pivotal descriptor of the amplitude of whisker displacement, the velocity, is reflected in the rate of spike discharges. While phase-locked discharges occurred over the entire range of frequencies tested (10–600 Hz), the discharge rate increased with stimulus velocity only up to about 60 µm/ms, saturating at a mean rate of ~117 spikes/s. In addition, the results show that whisker movements of more than 500 Hz bandwidth may be encoded by phase-locked responses of small groups of cortical neurons. Thus, even single whiskers may transmit information about wide ranges of textural components owing to their set of different types of hair follicle mechanoreceptors.

Atrial fibrillation (AF) is the most common heart rhythm disorder. Transient postoperative AF can be elicited by high sympathetic nervous system activity. Catecholamines and serotonin cause arrhythmias in atrial trabeculae from patients with sinus rhythm (SR), but whether these arrhythmias occur in patients with chronic AF is unknown. We compared the incidence of arrhythmic contractions caused by norepinephrine, epinephrine, serotonin, and forskolin in atrial trabeculae from patients with SR and patients with AF. In the patients with AF, arrhythmias were markedly reduced for the agonists and abolished for forskolin, whereas maximum inotropic responses were markedly blunted only for serotonin. Serotonin and forskolin produced spontaneous diastolic Ca(2+) releases in atrial myocytes from the patients with SR that were abolished or reduced in myocytes from the patients with AF. For matching L-type Ca(2+)-current (ICa,L) responses, serotonin required and produced ∼ 100-fold less cAMP/PKA at the Ca(2+) channel domain compared with the catecholamines and forskolin. Norepinephrine-evoked ICa,L responses were decreased by inhibition of Ca(2+)/calmodulin-dependent kinase II (CaMKII) in myocytes from patients with SR, but not in those from patients with AF. Agonist-evoked phosphorylation by CaMKII at phospholamban (Thr-17), but not of ryanodine2 (Ser-2814), was reduced in trabeculae from patients with AF. The decreased CaMKII activity may contribute to the blunting of agonist-evoked arrhythmias in the atrial myocardium of patients with AF.

The corticostriatal axis is the main input stage of the basal ganglia and is crucial for their role in motor behavior. Synchronized oscillations might mediate interactions between cortex and striatum during behavior, yet direct evidence remains sparse. Here, we show that, during motor behavior, low- and high-frequency oscillations jointly couple cortex and striatum via cross-frequency interactions. We investigated neuronal oscillations along the corticostriatal axis in rats during rest and treadmill running. We found prominent theta and gamma oscillations in cortex and striatum, the peak frequencies of which scaled with motor demand. Theta and gamma oscillations were functionally coupled through phase-amplitude coupling. Furthermore, theta oscillations were phase coupled between structures. Together, local phase-amplitude coupling and corticostriatal theta phase coupling mediated the temporal correlation of gamma bursts between the cortex and striatum. The coordination of fast oscillations through coherent phase-amplitude coupling may be a general mechanism to regulate neuronal interactions along the corticostriatal axis and beyond.

High-frequency stimulation of the subthalamic nucleus (STN-HFS) is widely used as therapeutic intervention in patients suffering from advanced Parkinson’s disease. STN-HFS exerts a powerful modulatory effect on cortical motor control by orthodromic modulation of basal ganglia outflow and via antidromic activation of corticofugal fibers. However, STN-HFS-induced changes of the sensorimotor cortex are hitherto unexplored. To address this question at a genomic level, we performed mRNA expression analyses using Affymetrix microarray gene chips and real-time RT-PCR in sensorimotor cortex of parkinsonian and control rats following STN-HFS. Experimental parkinsonism was induced in Brown Norway rats by bilateral nigral injections of 6-hydroxydopamine and was assessed histologically, behaviorally, and electrophysiologically. We applied prolonged (23h) unilateral STN-HFS in awake and freely moving animals, with the non-stimulated hemisphere serving as an internal control for gene expression analyses. Gene enrichment analysis revealed strongest regulation in major histocompatibility complex (MHC) related genes. STN-HFS led to a cortical downregulation of several MHC class II (RT1-Da, Db1, Ba, and Cd74) and MHC class I (RT1CE) encoding genes. The same set of genes showed increased expression levels in a comparison addressing the effect of 6-hydroxydopamine lesioning. Hence, our data suggest the possible association of altered microglial activity and synaptic transmission by STN-HFS within the sensorimotor cortex of 6-hydroxydopamine treated rats.