Joerg F. Hipp

Large-scale cortical correlation structure of spontaneous oscillatory activity

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.

Increased functional connectivity indicates the severity of cognitive impairment in multiple sclerosis

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.

Cortical hypersynchrony predicts breakdown of sensory processing during loss of consciousness.

Intrinsic cortical dynamics modulates the processing of sensory information and therefore may be critical for conscious perception. 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.

Dissociating neuronal gamma-band activity from cranial and ocular muscle activity in EEG.

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.

The saccadic spike artifact in MEG

Electro- and magnetoencephalography (EEG/MEG) are the means to investigate the dynamics of neuronal activity non-invasively in the human brain. However, both EEG and MEG are also sensitive to non-neural sources, which can severely complicate the interpretation. The saccadic spike potential (SP) at saccade onset has been identified as a particularly problematic artifact in EEG because it closely resembles synchronous neuronal gamma band activity. While the SP and its confounding effects on EEG have been thoroughly characterized, the corresponding artifact in MEG, the saccadic spike field (SF), has not been investigated. Here we provide a detailed characterization of the SF. We simultaneously recorded MEG, EEG, gaze position and electrooculogram (EOG). We compared the SF in MEG for different saccade sizes and directions and contrasted it with the well-known SP in EEG. Our results reveal a saccade amplitude and direction dependent, lateralized saccadic spike artifact, which was most prominent in the gamma frequency range. The SF was strongest at frontal and temporal sensors but unlike the SP in EEG did not contaminate parietal sensors. Furthermore, we observed that the source configurations of the SF were comparable for regular and miniature saccades. Using distributed source analysis we identified the sources of the SF in the extraocular muscles. In summary, our results show that the SF in MEG closely resembles neuronal activity in frontal and temporal sensors. Our detailed characterization of the SF constitutes a solid basis for assessing possible saccadic spike related contamination in MEG experiments.

BOLD fMRI Correlation Reflects Frequency-Specific Neuronal Correlation

The brain-wide correlation of hemodynamic signals as measured with BOLD fMRI is widely studied as a proxy for integrative brain processes. However, the relationship between hemodynamic correlation structure and neuronal correlation structure 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.

Oscillatory MEG gamma band activity dissociates perceptual and conceptual aspects of visual object processing: a combined repetition/conceptual priming study.

We used a combined repetition/conceptual priming task to investigate attenuations of induced gamma-band activity (iGBA) due to prior experience. We hypothesized that distinguishable iGBA suppression effects can be related to the processing of (a) perceptual aspects, and (b) conceptual aspects of cortical object representations. Participants were asked to perform a semantic classification task with pictures of real world objects and their semantically corresponding words, using a design that isolated distinct levels of the neural suppression effect. By means of volumetric source analysis we located stimulus domain-specific iGBA repetition suppression effects (60-90 Hz) in temporal, parietal, and occipital areas of the human cortex. In contrast, domain-unspecific iGBA repetition suppression, corresponding to conceptual priming, was restricted to left temporal brain regions. We propose that the selective involvement of left temporal areas points to the activation of conceptual representations, whereas more posterior temporal, parietal, and occipital areas probably reflect perceptual aspects of higher-order visual object processing.

Noise alters beta-band activity in superior temporal cortex during audiovisual speech processing

Speech recognition is improved when complementary visual information is available, especially under noisy acoustic conditions. Functional neuroimaging studies have suggested that the superior temporal sulcus (STS) plays an important role for this improvement. The spectrotemporal dynamics underlying audiovisual speech processing in the STS, and how these dynamics are affected by auditory noise, are not well understood. Using electroencephalography, we investigated how auditory noise affects audiovisual speech processing in event-related potentials (ERPs) and oscillatory activity. Spoken syllables were presented in audiovisual (AV) and auditory only (A) trials at three different auditory noise levels (no, low, and high). Responses to A stimuli were subtracted from responses to AV stimuli, separately for each noise level, and these responses were subjected to the statistical analysis. Central ERPs differed between the no noise and the two noise conditions from 130 to 150 ms and 170 to 210 ms after auditory stimulus onset. Source localization using the local autoregressive average procedure revealed an involvement of the lateral temporal lobe, encompassing the superior and middle temporal gyrus. Neuronal activity in the beta-band (16 to 32 Hz) was suppressed at central channels around 100 to 400 ms after auditory stimulus onset in the averaged AV minus A signal over the three noise levels. This suppression was smaller in the high noise compared to the no noise and low noise condition, possibly reflecting disturbed recognition or altered processing of multisensory speech stimuli. Source analysis of the beta-band effect using linear beamforming demonstrated an involvement of the STS. Our study shows that auditory noise alters audiovisual speech processing in ERPs localized to lateral temporal lobe and provides evidence that beta-band activity in the STS plays a role for audiovisual speech processing under regular and noisy acoustic conditions.

Functionally specific oscillatory activity correlates between visual and auditory cortex in the blind

Many studies have shown that the visual cortex of blind humans is activated in non-visual tasks. However, the electrophysiological signals underlying this cross-modal plasticity are largely unknown. Here, we characterize the neuronal population activity in the visual and auditory cortex of congenitally blind humans and sighted controls in a complex cognitive task. We recorded magnetoencephalographic responses from participants performing semantic categorization of meaningful sounds that followed the presentation of a semantically related or unrelated haptic object. Source analysis of the spectrally resolved magnetoencephalography data revealed that: (i) neuronal responses to sounds were stronger and longer lasting in the auditory cortex of blind subjects; (ii) auditory stimulation elicited strong oscillatory responses in the visual cortex of blind subjects that closely resembled responses to visual stimulation in sighted humans; (iii) the signal in the gamma frequency range was modulated by semantic congruency between the sounds and the preceding haptic objects; and (iv) signal power in the gamma range was correlated on a trial-by-trial basis between auditory and visual cortex in blind subjects, and the strength of this correlation was modulated by semantic congruency. Our results suggest that specifically oscillatory activity in the gamma range reflects non-visual processing in the visual cortex of blind individuals. Moreover, our results provide evidence that the deprived visual cortex is functionally integrated into a larger network that serves non-visual functions.

Altered Intrinsic Neuronal Interactions in the Visual Cortex of the Blind

In congenital blindness, the brain develops under severe sensory deprivation and undergoes remarkable plastic changes in both structure and function. Visually deprived occipital cortical regions are histologically and morphologically altered and exhibit a strikingly remodeled functional state: absolute levels of neural activity are heightened and are modulated by nonvisual sensory stimulation as well as higher cognitive processes. However, the neuronal mechanisms that underlie this altered functional state remain largely unknown. Here, we show that the visual cortex of the congenitally blind exhibits a characteristic gain in frequency-specific intrinsic neuronal interactions. We studied oscillatory activity in 11 congenitally blind humans and matched sighted control subjects with magnetoencephalography at rest. We found increased spontaneous correlations of delta band (1–3 Hz) and gamma band (76–128 Hz) oscillations across the visual cortex of the blind that were functionally coupled. Local delta phase modulated gamma amplitude. Furthermore, classical resting rhythms (8–20 Hz) were reduced in amplitude but showed no altered correlation pattern. Our results suggest that both decreased inhibition and circuit mechanisms that support active processing are intrinsic features underlying the altered functional state of the visual cortex in congenitally blind individuals.