PROJECT SUMMARY / ABSTRACT Epilepsy is an often debilitating neurological condition affecting 3 million Americans and more than 50 million people across the globe. Focal epileptic seizures start in specific brain regions due to abnormal patterns of activity in very specific subpopulations of neurons.
PROJECT SUMMARY The execution of learned sequential motor behaviors, like those involved in playing a well learned tune on the piano, are thought to be supported by precise sequences of neuronal activity in the brain. However, probing the ties between sequential neuronal activity, neuronal connectivity and behavior is challenging without methods for simultaneously observing and controlling neuronal activity with spatial and temporal precision.
This project will transfer a computational modeling technology, "StimVision", from the McIntyre Lab at Case Western Reserve University to the deep brain stimulation (DBS) group at Massachusetts General Hospital (MGH). DBS is currently used to treat severe obsessive-compulsive disorder (OCD) through high-frequency electrical stimulation of the ventral internal capsule/ventral striatum (VC/VS). VC/VS is a complex brain region containing white matter tracts projecting to multiple frontal cortical regions.
Project Summary/Abstract The hippocampus is one of a select few brain regions that retain the ability to generate neurons in adulthood. Research in human patients and animal models suggests that increases and decreases in neurogenesis alter memory function and contribute to the etiology and treatment of emotional disorders. Despite almost 15 years of research linking adult neurogenesis to memory and emotional regulation, almost nothing is known about the circuit and coding mechanisms through which adult neurogenesis influences these processes.
The computational properties of the human brain arise from an intricate interplay between billions of neurons connected in complex networks. However, our ability to study these networks in healthy human brain is limited by the necessity to use noninvasive technologies. This is in contrast to animal models where a rich, detailed view on the cellular level brain function has become available due to recent advances in microscopic optical imaging and genetics.
Project Description Functional MRI (fMRI) based on the blood oxygenation level dependent (BOLD) contrast has become a powerful neuroimaging modality and has gained a prominent position in neuroscience for imaging brain activation at working state and functional connectivity at rest. However, most of fMRI research focus on functional mapping of brain activity at the system level with macroscopic scale. Recently, high-resolution fMRI at ultrahigh field has shown the feasibility of mapping the functional activity of elementary computational units from ocular dominance to orientation column.
PROJECT SUMMARY Our knowledge of signal processing in various parts of the human brain has been heavily influenced by non- invasive functional magnetic resonance imaging (fMRI) experiments. FMRI infers the location and selectivity of neural activity from vascular signals. However, brain circuits are much more complex than regional differences in neuronal selectivity. Specifically, the largest part of the brain (neocortex) accounts for up to 80% of the brain volume and is divided into six distinct layers. Specific computations, e.g., local processing vs. feedforward inputs vs. vs.
The blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI) fluctuations used to map functional connectivity contain a wealth of information about neural activity and physiological processes in the brain. Most functional connectivity studies wish to detect time-varying activity related to cognition and information processing, and view the presence of other contributors to the spontaneous BOLD fluctuations as a complication.
Project Summary / Abstract A major obstacle in the study of human brain function is that we currently have limited understanding of how the measurements made by different instruments, such as fMRI and EEG, relate to one another and to the underlying neuronal circuitry. Significant efforts have led to development of models within various specialist fields, but fragmentation has held us back from advancing our interpretation of the spatiotemporal characteristics of non-invasive imaging signals.
PROJECT SUMMARY/ABSTRACT All fMRI signals have a vascular origin, and this has been believed to be a major limitation to precise spatiotemporal localization of neuronal activation when using hemodynamic functional contrast such as BOLD. However, significant recent discoveries made using powerful ultrahigh-resolution optical imaging techniques have challenged this belief. Unfortunately these measures require invasive procedures and therefore cannot be performed in humans.
