Brain connectivity plays a major role in the encoding, transfer, and integration of sensory information. Interregional synchronization of neural oscillations in the γ-frequency band has been suggested as a key mechanism underlying perceptual integration. In a recent study, we found evidence for this hypothesis showing that the modulation of interhemispheric oscillatory synchrony by means of bihemispheric high-density transcranial alternating current stimulation (HD-TACS) affects binaural integration of dichotic acoustic features. Here, we aimed to establish a direct link between oscillatory synchrony, effective brain connectivity, and binaural integration. We experimentally manipulated oscillatory synchrony (using bihemispheric γ-TACS with different interhemispheric phase lags) and assessed the effect on effective brain connectivity and binaural integration (as measured with functional MRI and a dichotic listening task, respectively). We found that TACS reduced intrahemispheric connectivity within the auditory cortices and antiphase (interhemispheric phase lag 180°) TACS modulated connectivity between the two auditory cortices. Importantly, the changes in intra- and interhemispheric connectivity induced by TACS were correlated with changes in perceptual integration. Our results indicate that γ-band synchronization between the two auditory cortices plays a functional role in binaural integration, supporting the proposed role of interregional oscillatory synchrony in perceptual integration.

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Transcranial ultrasonic stimulation (TUS) is rapidly emerging as a promising non-invasive neuromodulation technique. TUS is already well-established in animal models, and now stimulation protocols that optimize neuromodulatory efficacy for human application are required. One promising protocol, pulsed at 1000 Hz, has consistently resulted in motor cortical inhibition. At the same time, a parallel research line has highlighted the potentially confounding influence of peripheral auditory stimulation arising from pulsing TUS at audible frequencies. Across four experiments, one preregistered, at three independent institutions, we employed tightly matched control conditions to disentangle direct neuromodulatory effects of TUS from those driven by the salient auditory confound in a combined transcranial ultrasonic and magnetic stimulation paradigm. We replicated motor cortical inhibition following TUS, but showed through both controls and manipulation of stimulation intensity, duration, and auditory masking conditions that this inhibition was driven by peripheral auditory stimulation rather than direct neuromodulation. This study highlights the substantial impact of the auditory confound, invites a reevaluation of prior findings, and calls for appropriate control conditions in future TUS work. Only when direct effects are disentangled from those driven by peripheral confounds can TUS fully realize its potential for neuroscientific research and clinical applications.

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