Neuroimaging Technologies Across Scales

Abstract Ultrasound (US) neuromodulation has received increased attention in recent years due to its unique ability to non-invasively activate and inhibit neurons. However, the mechanisms of US neuromodulation are not fully understood, and little is known about the optimal parameters that elicit neuromodulation. In this proposal, we will test a recently proposed model of US neuromodulation at the cellular level using patch clamp methods on pyramidal and interneurons, which have differing characteristics that we hypothesize will cause them to respond differently to US.

Project Summary / Abstract In an exciting era of growth in the use of non-invasive brain stimulation, new methods and applications are being disseminated widely with an increasing number of FDA approvals and equipment designed to probe or modulate the brain in fascinating new ways. The problem with this growing enthusiasm is that there are too few studies that have evaluated how tools such as transcranial magnetic stimulation (TMS) induce functional activation throughout a human brain, especially outside of the motor system.

PROJECT SUMMARY - UNIVERSITY OF NORTH CAROLINA-CHAPEL HILL, FROHLICH The alpha oscillation is a thalamo-cortical rhythm (8-12 Hz) that serves important functional roles in cognition and behavior. Transcranial alternating current stimulation (tACS) has been shown to alter cortical alpha oscillations and associated cognitive function in healthy human participants. However, it remains unclear how tACS engages and modulates thalamo-cortical oscillations as a function of stimulation dose (frequency, amplitude, and duration).

7. PROJECT SUMMARY Background. Electro- and magneto-encephalographic (EEG/MEG) responses to a stimulus are systematically attenuated– by up to 80%– if the same stimulus was presented less than 8-12 seconds ago. This dynamic modulation of response amplitude to identical stimuli is one of the most striking and fundamental properties of the EEG/MEG signal.

Project Summary The primary goal of this application is to elucidate the neural basis of resting-state functional magnetic resonance imaging (rsfMRI) signal using multi-modal approaches including multi-echo (ME)- rsfMRI, MR-compatible calcium signal recording, optogenetics and multi-laminar electrophysiology in awake rats. Despite the prominent role of rsfMRI in studying brain network function in health and disease, the neural basis of rsfMRI signal remains poorly understood.

Project Summary / Abstract: The blood oxygenation level dependent (BOLD) functional Magnetic Resonance Imaging (fMRI) signal source has been long debated since the invention of fMRI in the early 90s. While fMRI is one of the most successful technologies utilized in numerous studies, the debate over the source of fMRI signal source continue to generate controversies over the utility of fMRI and the interpretation of fMRI studies.

Abstract Resting state functional magnetic resonance imaging (rs-fMRI) is an important modality for imaging the human brain. Capturing fluctuations in the blood oxygen level dependent (BOLD) signal while the brain is `at rest', rs- fMRI can detect distant, and often bilaterally-symmetric regions where activity is synchronized. Such regions are inferred to have `functional connectivity', and patterns of these networks have been found to be altered in a wide range of otherwise indistinguishable disease states.

The six layers of cortex form distinct computational units that together govern the information flow and processing required for complex behavior. Hence, unravelling the brain's computational strategies requires understanding the layer-specific organization of the neocortex. Until recently, layer-resolved recordings have been confined to animal models, ignoring specific properties of the human brain and limiting our ability to study uniquely human functions such as language.

Abstract While functional magnetic resonance (fMRI) has proved invaluable for identifying where in the brain activation is occurring during a particular task, it has had less to say about how the dynamics of that activation actually contribute to task performance. Indeed, because of the belief that fMRI signals are sluggish and temporally imprecise, fMRI experimental paradigms traditionally have used sustained block designs which deliberately preclude measuring the rapid changes in sensory and motor signals that underlie everyday actions.

PROJECT SUMMARY Measures of functional magnetic resonance imaging (fMRI) functional connectivity – correlated blood oxygen level dependent (BOLD) responses – are fundamental to understanding the circuit-level mechanisms of brain function and dysfunction. The use of fMRI functional connectivity for understanding long-range dynamic interaction between areas is limited, however, because the physiological basis of this measure is unknown. This is because our knowledge is limited to correlative relationships between neural activity and BOLD functional connectivity.