Selective modulation of interhemispheric functional connectivity by HD-tACS shapes perception

Abstract

Oscillatory neuronal synchronization between cortical areas has been suggested to constitute a flexible mechanism to coordinate information flow in the human cerebral cortex. However, it remains unclear whether synchronized neuronal activity merely represents an epiphenomenon or whether it is causally involved in the selective gating of information. Here, we combined bilateral high-density transcranial alternating current stimulation (HD-tACS) at 40 Hz with simultaneous electroencephalographic (EEG) recordings to study immediate electrophysiological effects during the selective entrainment of oscillatory gamma-band signatures. We found that interhemispheric functional connectivity was modulated in a predictable, phase-specific way: In-phase stimulation enhanced synchronization, anti-phase stimulation impaired functional coupling. Perceptual correlates of these connectivity changes were found in an ambiguous motion task, which strongly support the functional relevance of long-range neuronal coupling. Additionally, our results revealed a decrease in oscillatory alpha power in response to the entrainment of gamma band signatures. This finding provides causal evidence for the antagonistic role of alpha and gamma oscillations in the parieto-occipital cortex and confirms that the observed gamma band modulations were physiological in nature. Our results demonstrate that synchronized cortical network activity across several spatiotemporal scales is essential for conscious perception and cognition.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1. Procedure and tACS electrode montage.

(A) Left: Alternating presentation of two displays with diagonal tokens. Right: All subjects perceived either vertical or horizontal motion with spontaneous perceptual reversals. (B) The experiment was conducted on two separate days (for in- and anti-phase session). The SAM was presented during sham, stimulation, and post blocks and was interleaved with six RS recordings. RS3/4 and RS4/5 were separated by 10-minute intervals. (C) Electrode montage: The output signals of the tACS-stimulator were split with several Y-connectors and fed into 10 Ag/AgCl electrodes (common impedance

Figure 2. Stroboscopic alternative motion stimulus.

(A) Grand-mean coherence average (sham and post, both sessions) over electrode pair-of-interest (inset: electrode layout, pair-of-interest highlighted in red, dashed lines in topographies indicate the symmetry axis) during vertical (blue) and horizontal (red) motion perception (mean ± SEM). See also Data S1. (B) Relative coherence increases during horizontal motion perception. The topography depicts the statistical map of the coherence increase (black dots highlight the significant electrode cluster). (C) Gamma-coherence (γ1–γ3) increase by (+9.5%±3.2%) during horizontal motion perception. (D) Gamma-band power did not differ significantly between both percepts at the same electrodes. (E) Source reconstruction of gamma activity (60±10 Hz) for the vertical percept as compared to the resting state baseline. (F) Source reconstruction for the horizontal percept as compared to baseline.

Figure 3. Behavioral results.

(A) The MR modulation during the in- (green) and anti-phase (orange) session. The dashed black line depicts the average sham baseline (mean ± SEM). The star indicates the significant difference as revealed by a two-way RM-ANOVA with planned contrasts (Data S1; Table S1). (B) The switch rate across sessions and conditions (same conventions as in (A)).

Figure 4. Modulation of interhemispheric coherence during stimulation.

(A) Grand mean coherence average over four posterior channel pairs: The solid black line depicts average coherence during sham (mean ± SEM). Notch filtering in the γ1-band was applied to all conditions (dark-grey shaded, estimates were obtained after spectral smoothing and not used for statistical analyses; dashed box highlights utilized frequency bands). Dashed lines indicate vertical motion percepts; solid lines depict horizontal percepts. See also Data S1. (B) Relative γ2/3-coherence increase during the horizontal percept (with respect to the vertical percept) revealed that the binding-related coherence increase was still present during tACS (same conventions as in Figure 2C). (C) Absolute γ2/3-power values indicated that coherence changes were not related to gamma-power changes. (D) Coherence change over time (pair of interest). The black dashed line indicated the mean sham value. See also Data S1. (E) Spatial distribution for the coherence modulation. Upper left: In-phase stimulation. Upper right: Anti-phase stimulation. Lower: The Z-score map indicates a significant difference between in- and anti-phasic tACS located over parieto-occipital electrode pairs. Dots highlight the significant cluster. (F) Cluster-based permuted correlation analysis: A baseline corrected motion index (MI)  =  (MRInPhase − MRShamIn) − (MRAntiPhase − MRShamAnti) was correlated with the baseline corrected ΔCoherence of γ2-coherence values (CohIn-Phase − CohAnti-Phase). Upper panel: The black dots in the topography depict the significant cluster (p = 0.008). Lower panel: Regression line fitted through the mean coherence values as obtained from the cluster test. Dots depict individual subjects. Solid red line depicts the linear regression. (G) Cluster-based permuted correlation analysis indicated that subjects with an individual gamma coherence peak close to the stimulation frequency (40 Hz) exhibit the largest coherence modulation (p = 0.049). (H) Mean gamma power change over time (Data S1). (I) Source reconstruction of gamma activity during in- (green) and anti-phase (orange) stimulation as compared to baseline.

Figure 5. Outlasting coherence effects are frequency and polarity specific.

(A) Coherence spectra during RS1 (black), after in-phase stimulation (RS3, green), and after anti-phase stimulation (RS3, orange) are depicted. For further analyses, the complete gamma-band range (γ1–3, dashed box) was used. (B) Time course of gamma-band coherence (relative to RS1 during the in-phase session) over six resting state intervals (RS1–6; Data S1). The topography highlights a significant difference after stimulation (RS3) between in-phase and anti-phase stimulation. The cluster had its maximum over parieto-occipital areas (p = 0.039; dots highlight the significant cluster). (C) Cluster-based permuted correlation analysis indicated a significant positive correlation between the γ2-coherence modulation during and the γ1,2-coherence modulation after stimulation (p = 0.026). Same conventions as in Figure 4F, all values were baseline corrected. Black dots in topography highlight the significant cluster. (D) Gamma power time course (relative to RS1 of the in-phase session; Data S1).

Figure 6. Signatures of gamma-band entrainment by tACS.

(A) Results of Rao's spacing test, indicating an increase in non-uniform gamma phase distributions over parieto-occipital cortical areas during tACS. (B) Left: Results of Kuiper's test for unequal distribution of instantaneous phase angles in the gamma-band between sham/stimulation and sham/post, indicate a parieto-occipital maximum (statistical significance is assumed when >26 tests reach p<0.0016). Right: The same analysis applied to delta, alpha, and beta-bands. (C) Cluster analysis revealed a significant entropy decrease under parieto-occipital electrodes during stimulation as compared to sham (p = 0.004), but not when sham was compared to the post condition (p>0.05). A comparison of stimulation and post confirmed this difference (cluster test: p = 0.002). See also Data S1. (D) Relative entropy change at a posterior midline electrode during stimulation (dark grey line) and post (light grey line) indicated that the entropy decrease is not confined to the gamma-band (Data S1).

Figure 7. 40 Hz tACS modulates alpha oscillations.

(A) Mean alpha power (8–12 Hz) over time at lateral parieto-occipital electrodes. Visual stimulation induced a prominent alpha decrease, thus, topographies over time were highly similar. Note that the topography during tACS was less attenuated over lateral EEG sensors (corresponding to (B), upper panel; Data S1). (B) The topography and spectrum depict the significantly reduced alpha power over lateral parieto-occipital areas (dots depict significant cluster, p = 0.014; grey shaded area depicts 8–12 Hz range). (C) Schematic amplitude-envelope correlation analysis: I. 8–12 Hz band-pass filtered signal (black) and the corresponding envelope (red). II. Band-pass filtered signal in the γ2-range (black) and the corresponding envelope (blue). III. The gamma envelope (blue) was filtered in the alpha range and then its envelope (green) extracted. IV. Superposition of alpha amplitude (red) and gamma envelope (green). (D) Upper: The Z-score map located the main difference between sham and tACS conditions to lateral parieto-occipital sensors. Lower: Relative Fisher-Z-transformed correlation values highlight the transient increase in alpha-gamma amplitude correlations during tACS. See also Data S1.