The brain-wide correlation of hemodynamic signals as measured with BOLD fMRI is widely studied as a proxy for integrative brain processes 1–3. However, the relationship between hemodynamic ...correlation structure and neuronal correlation structure 4–6 remains elusive. We investigated this relation using BOLD fMRI and spatially co-registered, source-localized MEG in resting humans. We found that across the entire cortex BOLD correlation reflected the co-variation of frequency-specific neuronal activity. Resolving the relation between electrophysiological and hemodynamic correlation structures locally in cortico-cortical connection space, we found that this relation was subject specific and even persisted on the centimeter scale. At first sight, this relation was strongest in the alpha to beta frequency range (8–32 Hz). However, correcting for differences in signal-to-noise ratios across electrophysiological frequencies, we found that the relation extended over a broad frequency range from 2 to 128 Hz. Moreover, we found that the frequency with the tightest link to BOLD correlation varied across cortico-cortical space. For every cortico-cortical connection, we show which specific correlated oscillations were most related to BOLD correlations. Our work provides direct evidence for the neuronal origin of BOLD correlation structure. Moreover, our work suggests that, across the brain, BOLD correlation reflects correlation of different types of neuronal network processes and that frequency-specific electrophysiological correlation provides information about large-scale neuronal interactions complementary to BOLD fMRI.
•Electrophysiological correlation structure predicts BOLD fMRI correlation structure•BOLD fMRI and electrophysiology correlate on the single-subject level•BOLD-electrophysiology correlation extends from 2 to 128 Hz•Most predictive electrophysiological frequency varies with cortical connection
Brain-wide correlations of spontaneous BOLD fMRI signals are widely used to study large-scale neuronal interactions. Hipp and Siegel show that BOLD correlation in the human brain reflects the correlation of frequency-specific neuronal population activity.
Transcranial electric stimulation (tES) is a promising tool to non-invasively manipulate neuronal activity in the human brain. Several studies have shown behavioral effects of tES, but stimulation ...artifacts complicate the simultaneous investigation of neural activity with EEG or MEG. Here, we first show for EEG and MEG, that contrary to previous assumptions, artifacts do not simply reflect stimulation currents, but that heartbeat and respiration non-linearly modulate stimulation artifacts. These modulations occur irrespective of the stimulation frequency, i.e. during both transcranial alternating and direct current stimulations (tACS and tDCS). Second, we show that, although at first sight previously employed artifact rejection methods may seem to remove artifacts, data are still contaminated by non-linear stimulation artifacts. Because of their complex nature and dependence on the subjects' physiological state, these artifacts are prone to be mistaken as neural entrainment. In sum, our results uncover non-linear tES artifacts, show that current techniques fail to fully remove them, and pave the way for new artifact rejection methods.
•Systematic characterization of tES artifacts on simultaneously recorded EEG and MEG.•tES artifacts are non-linearly modulated by heartbeat and respiration for EEG and MEG.•Current artifact rejection methods fail to fully remove tES artifacts.
EEG is the most common technique for studying neuronal dynamics of the human brain. However, electromyogenic artifacts from cranial muscles and ocular muscles executing involuntary microsaccades ...compromise estimates of neuronal activity in the gamma band (>30 Hz). Yet, the relative contributions and practical consequences of these artifacts remain unclear. Here, we systematically dissected the effects of these different artifacts on studying visual gamma-band activity with EEG on the sensor and source level, and show strategies to cope with these confounds. We found that cranial muscle activity prevented a direct investigation of neuronal gamma-band activity at the sensor level. Furthermore, we found prolonged microsaccade-related artifacts beyond the well-known transient EEG confounds. We then show that if electromyogenic artifacts are carefully accounted for, the EEG nonetheless allows for studying visual gamma-band activity even at the sensor level. Furthermore, we found that source analysis based on spatial filtering does not only map the EEG signals to the cortical space of interest, but also efficiently accounts for cranial and ocular muscle artifacts. Together, our results clarify the relative contributions and characteristics of myogenic artifacts confounding visual gamma-band activity in EEG, and provide practical guidelines for future experiments.
Little is known about the brain-wide correlation of electrophysiological signals. We found that spontaneous oscillatory neuronal activity exhibited frequency-specific spatial correlation structure in ...the human brain. We developed an analysis approach that discounts spurious correlation of signal power caused by the limited spatial resolution of electrophysiological measures. We applied this approach to source estimates of spontaneous neuronal activity reconstructed from magnetoencephalography. Overall, correlation of power across cortical regions was strongest in the alpha to beta frequency range (8–32 Hz) and correlation patterns depended on the underlying oscillation frequency. Global hubs resided in the medial temporal lobe in the theta frequency range (4–6 Hz), in lateral parietal areas in the alpha to beta frequency range (8–23 Hz) and in sensorimotor areas for higher frequencies (32–45 Hz). Our data suggest that interactions in various large-scale cortical networks may be reflected in frequency-specific power envelope correlations.
Normal brain function requires the dynamic interaction of functionally specialized but widely distributed cortical regions. Long-range synchronization of oscillatory signals has been suggested to ...mediate these interactions within large-scale cortical networks, but direct evidence is sparse. Here we show that oscillatory synchronization is organized in such large-scale networks. We implemented an analysis approach that allows for imaging synchronized cortical networks and applied this technique to EEG recordings in humans. We identified two networks: beta-band synchronization (∼20 Hz) in a fronto-parieto-occipital network and gamma-band synchronization (∼80 Hz) in a centro-temporal network. Strong perceptual correlates support their functional relevance: the strength of synchronization within these networks predicted the subjects' percept of an ambiguous audiovisual stimulus as well as the integration of auditory and visual information. Our results provide evidence that oscillatory neuronal synchronization mediates neuronal communication within frequency-specific, large-scale cortical networks.
► Demonstration of oscillatory synchronization in large-scale cortical networks ► Strength of synchronization predicts perception of an ambiguous stimulus ► Strength of synchronization predicts cross-modal integration of sensory input ► An analysis approach for imaging synchronized large-scale cortical networks
Intrinsic 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.
► Propofol induces hypersynchronous cortical activity in the 8–14 Hz frequency range ► Hypersynchrony increases parametrically with progressive loss of consciousness (LOC) ► During LOC, early cortical responses persist but late responses break down ► Drug-induced alpha activity may suppress routing of sensory information
Liver cells are key players in innate immunity. Thus, studying primary isolated liver cells is necessary for determining their role in liver physiology and pathophysiology. In particular, the ...quantity and quality of isolated cells are crucial to their function. Our aim was to isolate a large quantity of high-quality human parenchymal and non-parenchymal cells from a single liver specimen.
Hepatocytes, Kupffer cells, liver sinusoidal endothelial cells, and stellate cells were isolated from liver tissues by collagenase perfusion in combination with low-speed centrifugation, density gradient centrifugation, and magnetic-activated cell sorting. The purity and functionality of cultured cell populations were controlled by determining their morphology, discriminative cell marker expression, and functional activity.
Cell preparation yielded the following cell counts per gram of liver tissue: 2.0 ± 0.4 × 10(7) hepatocytes, 1.8 ± 0.5 × 10(6 )Kupffer cells, 4.3 ± 1.9 × 10(5) liver sinusoidal endothelial cells, and 3.2 ± 0.5 × 10(5) stellate cells. Hepatocytes were identified by albumin (95.5 ± 1.7%) and exhibited time-dependent activity of cytochrome P450 enzymes. Kupffer cells expressed CD68 (94.5 ± 1.2%) and exhibited phagocytic activity, as determined with 1 μm latex beads. Endothelial cells were CD146(+) (97.8 ± 1.1%) and exhibited efficient uptake of acetylated low-density lipoprotein. Hepatic stellate cells were identified by the expression of α-smooth muscle actin (97.1 ± 1.5%). These cells further exhibited retinol (vitamin A)-mediated autofluorescence.
Our isolation procedure for primary parenchymal and non-parenchymal liver cells resulted in cell populations of high purity and quality, with retained physiological functionality in vitro. Thus, this system may provide a valuable tool for determining liver function and disease.
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.
Corrosion is normally an undesirable phenomenon in engineering applications. In the field of biomedical applications, however, implants that 'biocorrode' are of considerable interest. Deploying them ...not only abrogates the need for implant-removal surgery, but also circumvents the long-term negative effects of permanent implants. In this context magnesium is an attractive biodegradable material, but its corrosion is accompanied by hydrogen evolution, which is problematic in many biomedical applications. Whereas the degradation and thus the hydrogen evolution of crystalline Mg alloys can be altered only within a very limited range, Mg-based glasses offer extended solubility for alloying elements plus a homogeneous single-phase structure, both of which may alter corrosion behaviour significantly. Here we report on a distinct reduction in hydrogen evolution in Zn-rich MgZnCa glasses. Above a particular Zn-alloying threshold ( 28 at.%), a Zn- and oxygen-rich passivating layer forms on the alloy surface, which we explain by a model based on the calculated Pourbaix diagram of Zn in simulated body fluid. We document animal studies that confirm the great reduction in hydrogen evolution and reveal the same good tissue compatibility as seen for crystalline Mg implants. Thus, the glassy Mg60+xZn35−xCa5 (0≤x≤7) alloys show great potential for deployment in a new generation of biodegradable implants.
Power correlations of orthogonalized signals have recently been introduced for MEG as a powerful tool to non-invasively investigate functional connectivity in the human brain. Little is known about ...the applicability of this approach to EEG, and how compatible the results are between EEG and MEG. To address this, we systematically compared power correlations of simultaneously recorded and source co-registered 64-channel EEG and 275-channel MEG in resting human subjects. For both modalities, connectivity peaked at around 16Hz. For this frequency range, seed-based correlation maps showed comparable patterns across modalities, with generally more distinct patterns for MEG. A brain-wide pattern correlation analysis also revealed maximum similarity around 16Hz. Correcting for different signal-to-noise ratio (SNR) across frequencies and modalities revealed pattern correlation between modalities close to one across a broad frequency range from 1 to 32Hz and only slightly smaller for higher frequencies. The decrease above 32Hz likely reflected higher susceptibility to muscle artifacts for EEG than for MEG. Our results show that power correlation of orthogonalized signals is feasible for studying functional connectivity with 64-channel EEG. Furthermore, besides differences in SNR, for frequencies from about 8 to 32Hz, EEG and MEG measure the same correlation patterns across the entire brain.
•Comparison between correlation structures of neuronal oscillations assessed with EEG and MEG•EEG provides access to spectral and spatially specific correlation structure.•MEG correlation structure is more distinct than EEG correlation structure.•If accounted for SNR, EEG and MEG yield highly similar correlation structure.•EEG is more susceptible to muscle activity.
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