Breaking the boundaries of interacting with the human brain using adaptive closed-loop stimulation.

The human brain is arguably one of the most complex systems in nature. To understand how it operates, it is essential to understand the link between neural activity and behavior. Experimental investigation of that link requires tools to interact with neural activity during behavior. Human neuroscience, however, has been severely bottlenecked by the limitations of these tools. While invasive methods can support highly specific interaction with brain activity during behavior, their applicability in human neuroscience is limited. Despite extensive development in the last decades, noninvasive alternatives have lacked spatial specificity and yielded results that are commonly fraught with variability and replicability issues, along with relatively limited understanding of the neural mechanisms involved. Here we provide a comprehensive review of the state-of-the-art in interacting with human brain activity and highlight current limitations and recent efforts to overcome these limitations. Beyond crucial technical and scientific advancements in electromagnetic brain stimulation, new frontiers in interacting with human brain activity such as task-irrelevant sensory stimulation and focal ultrasound stimulation are introduced. Finally, we argue that, along with technological improvements and breakthroughs in noninvasive methods, a paradigm shift towards adaptive closed-loop stimulation will be a critical step for advancing human neuroscience.