Monitor Neural Activity

Project Summary/Abstract The distributed brain network of the hippocampus supports memory and related cognitive abilities. Disruptions of this network occur in many neurological disorders such as epilepsy, brain injury, and neurodegenerative disease. Brain stimulation targeting the human hippocampal network can produce long-lasting improvements of memory ability, with corresponding increases in brain-activity markers of network function.

Project Summary/Abstract Because activity-dependent plasticity is ubiquitous in the CNS, brain stimulation may have long-term effects on areas to which the stimulated area connects. These effects have received little attention. Nevertheless, recent appreciation of the long-term role of cortex in shaping spinal cord pathways suggests that the long-term spinal effects of cortical stimulation are likely to be substantial. In fact, weak electrical cortical stimulation (ECS) of rat sensorimotor cortex has lasting spinal effects.

PROJECT SUMMARY / ABSTRACT Understanding how cognitively-relevant behavioral functions emerge from activity patterns of identified cell- types is predicated on the ability to record large-scale ensemble dynamics from genetically-identified and longitudinally-tracked neuronal populations across multiple brain regions and layers with high spatial and temporal resolution over behaviorally-relevant time-scales.

ABSTRACT Activity-sensitive fluorescent indicators and microscopy have proven valuable tools for measuring neuronal activity, but most forms of cellular microscopy can produce images of neurons only near the brain surface and generally only after removal of tissues overlying the brain surface, such as bone. Many neurons in neocortex are out of reach of cellular microscopy. Here we propose to optimize 3-photon (3P) excitation fluorescence imaging, a form of cellular microscopy, to enable deeper imaging into the brain.

1 Project Summary: The BRAIN 2025 Report, with the goal to “produce a dynamic picture of the functioning brain 2 by developing and applying improved methods for large-scale monitoring of neural activity” is directly 3 addressed by this application.

The brain is a massively interconnected network of specialized circuits. Three characteristics of these circuits make them particularly challenging: diversity of time scales, diversity of spatial scales, and heterogeneity. Understanding the brain therefore requires spanning these temporal and spatial scales and providing information about cell-types. We need to be able to record the activity of individual neurons across time to understand activity patterns on a millisecond timescale and how those patterns evolve with experience across hours, days, months and even years.

PROJECT SUMMARY The goal of this project is to understand the neurobiological underpinnings of the effects of ultrasound (US) on neural activity. US can modify action potential activity in neurons in vitro and in vivo without damaging neural tissue. This phenomenon can be applied in powerful new tools for basic and clinical neuroscience, with broad impact on public health issues related to mental and neurological disorders.

Project(Summary(/(Abstract! There is a need to understand the mechanisms of neural stimulation technologies (RFA-NS-18-018). The impact of such research increases with both the clinical relevance of a neuromodulation technology and the extent mechanisms are unknown. Spinal Cord Stimulation at kHz frequencies (kHz SCS) has undergone a meteoric clinical and market rise, in the absence of an accepted mechanistic hypothesis. The most peculiar feature of kHz SCS mechanistically is that rapid biphasic stimulation undermines traditional mechanisms of electrical stimulation.

Abstract Nonivasive stimulation of the brain in health and disease is an important goal of the Brain Initiative. Current methods include Transcranial Magnetic Stimulation (TMS), Transcranial Electric Stimulation (TES) and Transcranial Focused Ultrasound Stimulation (TFUS). The mechanisms of the perturbation effects are not well understood.

The use of transcranial magnetic stimulation (TMS) as a therapeutic intervention is FDA-cleared for treating depression, obsessive-compulsive disorder, and migraine, and shows promise for a host of other brain disorders. The appeal of TMS is its safety, non-invasiveness, and well-established capacity for modulating the activity of brain regions. In human subjects, that modulation is assessed only at the gross scale of behavioral, cognitive, or aggregate physiological effects (e.g. EMG, EEG, fMRI).