Neuroimaging Technologies Across Scales

PROJECT SUMMARY Blood-oxygenation-level-dependent functional magnetic resonance imaging (BOLD fMRI) is widely used in to study human brain function; however the cellular and molecular mechanisms underlying the BOLD signal remain poorly understood. The BOLD signal is highly complex as it represents disproportionate interactions of cerebral blood flow (CBF), cerebral blood volume (CBV), and cerebral metabolic rate of oxygen (CMRO2) during neuronal activation.

Principal Investigators(Last, first, middle):KLEINFELD, DAVID and ROSEN, BRUCE R. Functional magnetic resonant imaging (fMRI) is the only means to infer neuronal activity within the entire volume of the human brain. A powerful aspect of fMRI concerns coordinated fluctuations in the amplitude of blood oxygen level dependent (BOLD) signals across distant regions of the brain, which are interpreted as "resting-state functional connections". Here we address the underlying biophysical mechanism that underlies resting-state functional connectivity.

Intrinsic ‘functional connectivity’ (iFC), a measure of correlation between spontaneous fluctuations in the blood oxygen level dependent (BOLD) signal, reliably distinguish networks of cortical and subcortical areas during both rest and active task performance. iFC methods can map the functional architecture of the human brain in both healthy and pathological conditions, in high detail using as little as 5 minutes of data.

PROJECT SUMMARY Functional MRI (fMRI) is performed at a macroscopic scale of 1 to 3 millimeters spatial resolution. The term `mesoscale' has come to denote the resolution of a finer granularity of neuronal organization, to show functional organization across the depth and along the surface of the cortex. Mesoscale fMRI representation of neural activity, however, is not firmly established. A primary objective of this research is to evaluate fMRI's ability to accurately differentiate neuronal activity in cortical layers and columns.

Project Summary The main objective of the proposed research is to develop a wearable transcranial focused ultrasound (tFUS) environment that reversibly modulates (either elicits or suppresses) region-specific neural activities of the brain.

Project Abstract Completely noninvasive neuromodulation using focused ultrasound (FUS) offers the promise of precisely stimulating specific targets deep in the brain. FUS is already used to deliver precise ablations deep in the brain. A CT scan is currently used to calculate the phase aberration corrections. The focal spot is calibrated by imaging a 5°C temperature rise. Both the CT scan and tissue heating are unacceptable in normal volunteers. Beyond that, skulls with similar CT scans vary widely in their ultrasound attenuation.

Project Summary/Abstract: During the past two decades, functional Magnetic Resonance Imaging (fMRI) has become ubiquitous in studies of the human brain function. Similarly, Transcranial Magnetic Stimulation (TMS) has established its role as one of the most widely used neuromodulation techniques. Both of these methods have gained popularity due to their safe and noninvasive nature in addition to their wide availability.

This project will develop a low-noise transcranial magnetic stimulation (TMS) system. TMS is a technique for non-invasive brain stimulation using strong, brief magnetic pulses. TMS is widely used as a tool for probing brain function and is an FDA approved treatment for depression. A significant limitation of TMS, however, is that the magnetic pulse delivery is associated with a loud clicking sound as high as 140 dB resulting from electromagnetic forces. The loud noise significantly impedes both basic research and clinical applications of TMS.

Abstract This project seeks to develop a wireless, minimally invasive bi-directional deep brain stimulation technology based on remote heating of magnetic nanoparticles. Reliably modulating the activity of specific neuronal populations is essential to establishing causal links between neural firing patterns and observed behaviors. Electrical stimulation, as well as its recent non-invasive alternatives, ultrasound and electromagnetic induction, do not discriminate between cell types and have limited spatial resolution.

Aimed at revolutionizing our understanding of the brain, the BRAIN initiative calls for “improvement of existing non-invasive neuromodulation” techniques.