Efficiently searching through large tACS parameter spaces using closed-loop Bayesian optimization.

BACKGROUND: Selecting optimal stimulation parameters from numerous possibilities is a major obstacle for assessing the efficacy of non-invasive brain stimulation. OBJECTIVE: We demonstrate that Bayesian optimization can rapidly search through large parameter spaces and identify subject-level stimulation parameters in real-time. METHODS: To validate the method, Bayesian optimization was employed using participants' binary judgements about the intensity of phosphenes elicited through tACS. RESULTS: We demonstrate the efficiency of Bayesian optimization in identifying parameters that maximize phosphene intensity in a short timeframe (5 min for >190 possibilities). Our results replicate frequency-dependent effects across three montages and show phase-dependent effects of phosphene perception. Computational modelling explains that these phase effects result from constructive/destructive interference of the current reaching the retinas. Simulation analyses demonstrate the method's versatility for complex response functions, even when accounting for noisy observations. CONCLUSION: Alongside subjective ratings, this method can be used to optimize tACS parameters based on behavioral and neural measures and has the potential to be used for tailoring stimulation protocols to individuals

The neural representation of multisensory percepts: studying the integration of auditory and tactile stimuli in the somatosensory cortex

Multisensory integration is the constant process through which we combine information across different sensory modalities in order to better interpret our environment. In early models of multisensory integration, primary sensory areas were thought to almost exclusively treat information from their preferred sensory modality and contribute little to the integration process. However, a growing literature now describes cross-modal responses in primary sensory cortices and direct cortico-cortical connections between primary sensory cortices. Therefore, cortical multisensory integration may begin as early as the primary sensory regions. I built on this literature by examining how training on a multisensory integration task may alter vibrissal primary somatosensory cortex (vS1) responses to vibrotactile whisker stimulation and amplitude modulated pure tones. Unlike most previous studies, ours required the animal to identify a unique combination of vibrotactile and auditory stimulation in order to perform the task correctly. I used chronic in vivo two-photon imaging of vS1 to measure neural responses to stimuli throughout training on the Go/No-Go task. Responses of the same neural populations were compared prior to, during, and following task acquisition. Mice learned to correctly identify specific combinations of audio-tactile stimulation. I observed vS1 responses to vibrotactile stimuli and found a subset of neurons that were responsive to sounds. I also found neurons that responded only to a single multisensory combination. Training led to an increase in the proportion of responsive neurons during acquisition on all tasks and a decrease in the proportion of responsive neurons after training on the multisensory task. Most tracked neurons became either responsive or unresponsive during or after training. In contrast, very few neurons maintained constant response properties. While it remains unclear whether or how training may remodel local circuits, my findings suggest that training and experience lead to the recruitment of different populations of neurons in vS1 in a modality-specific manner

Imaging somatosensory cortex in rodents

The rodent somatosensory cortex has been investigated using a range of electrophysiological techniques, from intracellular recordings to electroencephalography. Nonetheless, their accessible location on the dorsal surface of the brain has more recently made the somatosensory areas popular models for the imaging-based investigation of cortical function. In this chapter, we will outline the general principles of two-photon microscopy applied to the functional study of the rodent somatosensory cortex. This technique allows recording the activity of hundreds of individual neurons simultaneously, with single-cell precision and while knowing their relative positions in the brain. We will place particular emphasis on long-term calcium imaging procedures on awake behaving mice and will introduce advantages and limitations of this technique. Our specific aim is to provide the reader with useful information regarding equipment and experimental procedures, from the choice of the calcium indicator to the post hoc analysis of imaging time series