Project summary: This project will develop and validate a comprehensive toolset of novel technologies for imaging axonal projections across scales, and will deploy this toolset to map a complex system of cortico- subcortical projections in the macaque and human brain. We will combine the complementary strengths of three innovative microscopy techniques.
ABSTRACT Single-cell transcriptomics has revolutionized our understanding of neuronal diversity and enabled high-throughput characterization of molecular cell types across brain areas and species.
SUMMARY We are proposing a new approach to a hybrid imaging modality that has been called “b+g” or “pamma-positron” Imaging [Gri07] that promises to simultaneously overcome 1) the sensitivity limits of single-gamma-ray-photon emission imaging, 2) the challenge of distinguishing between two different positron-emitting isotopes, and 3) the physics-based spatial resolution limits inherent in radioisotope imaging based on detection of positron- annihilation photons alone [Lan14].
Abstract Transcranial alternating current stimulation (TACS) non-invasively alters neuroelectric activity in the human brain by applying weak, time-varying electric currents to the scalp. It is increasingly being explored as a therapeutic intervention for various brain disorders by affecting pathological oscillatory neural activity. Despite its increasing popularity and rapidly growing literature, the basic physiological mechanisms of TACS are still not well understood.
Project Summary/Abstract We will develop a novel technology for noninvasive transcranial magnetic stimulation (TMS) of the human brain. TMS is a standard tool in experimental brain science and is FDA cleared for treatment of depression, obsessive- compulsive disorder, and migraine as well as pre-surgical brain mapping. However, the underlying high-power electromagnetic pulse technology has substantial limitations. First, the temporal waveform of conventional TMS pulses is exclusively sinusoidal with fixed shape and duration.
Abstract The ability to noninvasively modulate and image the brain with spatial and temporal precision is highly desirable for understanding brain circuits in health and disease. Transcranial magnetic stimulation (TMS) is a method for stimulating the superficial cortex with high spatial and temporal precision, and its effects can be aimed at deeper targets by leveraging the trans-synaptic connectivity of brain circuits. Functional magnetic resonance imaging (fMRI) has high spatial resolution but limited temporal precision, and the opposite holds for electroencephalography (EEG).
Project Summary We propose to develop and test a novel noninvasive neuromodulation technique integrating transcranial focused ultrasound (tFUS) with electrophysiological source imaging (ESI) to allow real-time evidence-based neuromodulation with spatio-temporal precision for brain research and managing brain conditions.
Abstract The dorsal cochlear nucleus (DCN) integrates auditory and somatosensory information through circuitry that modulates activity of the principal output neurons of the circuit, the fusiform cells. Fusiform cells receive somatosensory information via synapses on their apical dendrites and acoustic information via their basal dendrites. When somatosensory activation is combined with sound, the circuit can be strengthened or weakened depending on the order of the bimodal stimuli. This process is called stimulus timing dependent plasticity.
PROJECT SUMMARY . In psychiatry, we are limited by the mismatch between the diverse heterogeneity of the brain and the tools we have to treat it. We know from anatomic, cortical mapping, and imaging studies that every several millimeters of the brain is constituted, connected, and functions in a unique and significantly different manner.
Non-invasive methods for stimulating the human brain show great promise for safe, effective treatments of psychiatric and motor disorders, and are in widespread use for basic research on human behavior and cognition. One such method, transcranial magnetic stimulation (TMS), is the application of time-varying magnetic fields above the scalp that induce transient electrical fields in the brain. TMS clearly stimulates the brain and affects behavior, but we do not know why it works; its effects on neural activity within brain regions and networks are not understood at a biological level.
