Theory & Data Analysis Tools

Abstract Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation method which can alter brain activity in humans in a safe manner. Due its ease of application and ability to target specific brain regions, the repetitive application of TMS (rTMS) has the potential of augmenting or even replacing classic pharmacologic treatment-strategies. However, due to the enormous parameter space concerning its application (amplitude, coil position and orientation), optimal, i.e., personalized stimulation parameters for rTMS are very difficult to determine.

Project Summary Based on the gate-control theory of pain, traditional spinal cord stimulation (SCS) to treat chronic back/leg pain utilizes 40-60 Hz stimulation that activates spinal dorsal columns to elicit paresthesia over a patient’s painful region. This paresthesia-based SCS is only effective for 40-50% of patients with chronic back/leg pain, and the efficacy gradually reduces over time. A recent advance in SCS employs a high-frequency (10 kHz) biphasic stimulation waveform (HF10-SCS) at a subthreshold intensity that is paresthesia-free.

PROJECT SUMMARY/ABSTRACT: Electrical brain stimulation (EBS) is a FDA-approved neuromodulation therapy applied to several neurological disorders. However, the molecular basis of its efficacy remains unclear. Here we propose investigation of a glial mechanism for EBS mediated by astrocytes-derived extracellular vesicles (EVs). We recently discovered from both in vitro and in vivo experiments that electrical stimulation affects the release of EVs from astrocytes.

Project Abstract Electrical stimulation is widely used to activate and/or disrupt neuronal activity. Despite its critical importance in experimental and clinical neuroscience, at present, there is no validated method to predict which neural elements of the brain will be activated by a given stimulation regime. Based on our pilot studies, we propose here to develop a novel computational approach for predicting the specific neurons which will be activated by a given stimulation protocol, based on neuron shape, location, type and connectivity.

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 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).