Main achievements

Our studies on ICMs in the human brain have so far focused mainly on the analysis of coupling modes during attentional processing. We analysed ICMs in an MEG dataset from a task where participants reoriented their attention between three visual targets. We assessed how envelope ICMs were modulated around the onset of spontaneously occurring attentional shifts. We found the strongest modulations in the theta and alpha frequency range. Amplitude coupling was hereby increased between hubs of the visual and dorsal attention network. In particular, these coupling modulations were related to transient dynamics, i.e., oscillatory co-bursting, between cortical regions (Siems et al 2026).

Our studies on ICMs in the ferret we address the relation of coupling modes to behavior. In animals trained to a sensory detection task, we have studied how variations in local activity and functional connectivity determine performance (Galindo-Leon et al 2025a). Differences in power between hit and miss trials were observed primarily during the stimulus and response windows, whereas differences in phase ICMs emerged even before stimulus onset. Overall, our findings demonstrate that fluctuations in cortical network state – as reflected in large-scale coupling – play a critical role in shaping behavioral responses.

Transcranial alternating current stimulation (tACS) offers a promising opportunity to systematically manipulate coupling patterns in the human brain. So far, it is unknown whether tACS can be used to selectively modulate envelope ICMs. Therefore, we investigated the capability of amplitude-modulated tACS to experimentally manipulate the temporal co-modulation of the amplitude of beta oscillations (Fiene et al 2026). Our results indicate that incoherent amplitude-modulated tACS significantly reduced amplitude coupling compared to the coherent condition. This effect was most prominent for the stimulated beta frequency band and spatially specific to the targeted parieto-occipital regions.

We employ information-theoretic tools to analyse interactions between coupling modes, as well as their relation to sensory stimuli and behavior. We examined the causal relationship between the two types of ICMs using transfer entropy (Galindo-Leon et al 2025b). To evaluate how general our results are, we applied the same analysis to data recorded in the ferret and in humans using MEG. In both datasets, we observed a leading role of envelope ICMs over phase ICMs at low frequencies. Our analysis provides clear evidence that different coupling modes can causally influence each other.

As part of our theoretical work in the project we elaborated on the concept of multi-timescale dynamics in a Perspective article in a highly renowned international journal (Senkowski and Engel 2024).

For the analysis of ICMs we advanced several methodological approaches. In one approach, we aimed at improving the method for calculating phase coupling in EEG or MEG data. In such data, coupling between brain sources is typically calculated either on source or sensor level. We have developed a hybrid approach by a maximization of coupling between each source and the signal in sensor space (Göschl et al 2025). Computation using this approach is substantially faster than the respective approach calculated entirely on source level.

In our work on quantification of envelope ICMs, we have developed an analysis approach that better accounts for transient increases in signal amplitude, so-called bursts. A common assumption has been that bursts indicate an increase in periodic activity, i.e., oscillations. However, neuronal activity also features time-varying non-oscillatory activity that, when band-pass filtered, can exhibit similar temporal dynamics. We designed a novel analysis approach to directly address the distinction between oscillatory and non-oscillatory bursts in electrophysiological signals (Siems et al 2026).

Another novel element in our methodology is the use of tACS for the modulation of amplitude coupling. In this project we use, for the first time, stimulation waveform envelopes that mimic the natural dynamics of brain signals. We developed a proof-of-concept amplitude-modulated tACS protocol incorporating a beta band carrier frequency and an amplitude modulation frequency range between 0.1-5 Hz, consistent with scale-free envelope fluctuations (Fiene et al 2026). This approach can give important insight on whether amplitude coupling can be selectively modulated through amplitude modulation of the electrical stimulation signal.

To enable multi-site optogenetics in behaving animals, we have developed – in a cooperation with Prof. Patrick Ruther, IMTEK, University of Freiburg – novel thin-film, micro-scale LED probes for light stimulation in behaving animals. These μLED probes feature a dual-color setup which allows both optogenetic excitation and inhibition of neuronal populations if channelrhodopsins with different spectral sensitivity are used.

We provide the first evidence for the possibility to modulate envelope coupling in the human brain by tACS (Fiene et al 2026). The findings from our study provide causal evidence that amplitude co-modulation can be selectively manipulated via non-invasive brain stimulation techniques like amplitude-modulated tACS. This constitutes a significant advance in the field of non-invasive human neurostimulation. The ability to alter amplitude coupling independently of phase coupling underscores its role as a separate and functionally relevant mode of large-scale neural communication.

In addition to the use of novel protocols for the transcranial electrical stimulation, our studies also involve optogenetic protocols with sustained frequency- and amplitude-modulated stimuli that mimic the natural dynamics of brain signals. Our work so far shows that these protocols can be effective in modulating coupling modes in the cortical network. We believe that this approach could substantially advance the use of optogenetics for mesoscale network interventions.

Furthermore, our recent work provides the first evidence for causal interactions between different coupling modes – an issue that has not been addressed before. In line with theoretical predictions made earlier by our group, we observed a leading role of envelope ICMs over phase ICMs at low frequencies. Importantly, our results show systematic similarities of coupling mode interactions between ferret and human brains.