Monitor Neural Activity

The most widespread tool for measuring brain activity noninvasively in humans is functional magnetic resonance imaging (fMRI), which typically tracks changes in blood flow and oxygenation using the blood-oxygenation-level- dependent (BOLD) signal. Although BOLD is an indirect measure of neural firing, it has been shown to be a faithful measure of brain activation, yet the details of brain vascular anatomy and physiology are known to influence all fMRI signals including BOLD.

Project Summary/Abstract Selecting future actions based on previous experiences is key to an animal's survival. This process, known as action selection, depends on the proper function of cortical and subcortical basal ganglia circuits. Despite the importance of these regions for using previous experiences to inform upcoming motor choices, we do not understand the precise mechanisms by which these regions work together and the activity patterns they use to select actions.

Project Summary/Abstract Sex hormones are critical for sexual differentiation of the brain and body and diverse physiological processes across our lifespan. In particular, sex hormone signaling in the brain has been implicated in mood and emotional well-being, cognitive function, sexual orientation, gender identity, and libido. Many neurological and psychiatric conditions, including depression and anxiety, PTSD, Alzheimer’s disease, multiple sclerosis, Parkinson’s disease, ADHD, schizophrenia, and autism manifest with sex-skewed ratios or outcomes for poorly understood reasons.

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.

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.