Neuroimaging Technologies Across Scales

This project will develop transcranial magnetic stimulation coils with improved focality and depth (fdTMS). TMS is a technique for noninvasive brain stimulation using strong, brief magnetic pulses. TMS is widely used in the neurosciences as a tool for probing brain function and connectivity. Presently, TMS is FDA-approved for the treatment of depression and for pre-surgical cortical mapping, and is under study for other psychiatric and neurological disorders.

PROJECT SUMMARY Non-invasive stimulation of the cerebellum holds great promise for investigating brain function, and for diagnosing and treating a variety of brain disorders. Given the classical role of the cerebellum in motor control, it is not surprising that many studies have reported that cerebellar transcranial direct current stimulation (CB- tDCS) can be used to enhance motor function and mitigate the symptoms of ataxia, dystonia and essential tremor.

Project Summary: The goal of this proposal is to advance our ability to accurately infer the properties of neu- ral-level responses from the more coarse-grained information obtained with non-invasive imaging in humans. To achieve this goal, the project will capitalize on feature-selective cortical responses. For example, many neu- rons in visual cortex exhibit a tuning function such as a response profile in which firing rate is greatest for one orientation of a line, and falls off for orientations progressively less similar to that orientation.

Abstract This project will develop a novel infrared-based neuro-stimulation tool for specifically modulating neural circuitry. Transcranial infrared brain stimulation (TIBS) at 1064 nm will be developed as a new tool for non- invasive neuromodulation of the human brain. TIBS with low-power density (mW/cm2) and high-energy density (J/cm2) monochromatic laser is safe and can potentially modulate human brain function in a non-thermal manner.

Project Abstract Transcranial electrical stimulation (tES) methods, principally transcranial direct current simulation (tDCS) and transcranial alternating current stimulation (tACS) are neuromodulation techniques that have been the subject of great recent interest. In typical tDCS procedures a pair of large electrodes (e.g., 25cm2) is attached to the scalp and a constant current of 1-2 mA passed between them for periods of 10-30 min. In tACS, the constant current intensity is similar, but an alternating sinusoidal waveform is usually employed.

Project Summary The goal of the proposed project is to test in macaques a technique for non-invasive, safe, reversible, modulation of neuronal activity in small targeted regions of the primate brain. We have developed and tested in macaques a technique for transiently opening the blood-brain barrier (BBB) in targeted brain regions without causing any damage, using a clinically available focused ultrasound device in conjunction with circulating microbubbles.

ABSTRACT Despite the increasing use of transcranial magnetic stimulation (TMS) in both research and clinical practice, the field nonetheless lacks a theoretical framework to predict the impact of TMS on circuits. In this application, we propose to test the over-arching hypothesis that brain responses to TMS are governed by both the network control properties of the stimulation site and the functional context of the network during stimulation.

Project Abstract Completely noninvasive neuromodulation using focused ultrasound (FUS) offers the promise of precisely stimulating specific targets deep in the brain, at power levels commonly used for diagnostic imaging studies. Having a working mouse model to study neuromodulation with ultrasound is a critical need. The mouse model has a much wider array of immunohistochemical staining antibodies and known genetic markers to answer basic science questions than do larger animals.

PROJECT SUMMARY/ABSTRACT Although neurotechnologies are rapidly advancing, we lack a noninvasive, cell-type specific, and spatiotemporally regulated neuromodulation tool, which would radically change neuroscience research and enable clinically noninvasive brain stimulation with high spatiotemporal precision.

Non-invasive neuromodulation, such as transcranial direct current stimulation (tDCS), is emerging as an important therapeutic tool with documented effects on brain circuitry, yet little is understood about how it changes cognition. In particular, the challenge of how learning, or training, in one domain generalizes to unlearned or unpracticed domains has long been a focus of educational psychology.