Vision: Minimally invasive control and regulation of neural circuity
The brain is a network, and as we learn more about the pathophysiology of neurologic diseases, it is increasing clear that they are not isolated to a specific brain region but emerge from a dysfunction in brain networks. Neuronal atrophy in some of the main functional hubs of these networks, such as the hippocampus, thalamus, amygdala, and trigeminal nuclei, and abnormal connectivity among these regions, may underlie many of the symptoms and progression of neurologic diseases. Indeed, epilepsy, Alzheimer’s disease, Parkinson’s disease, neuropathic pain, and depression all exhibit loss of neurons and reduced neuronal density as well as altered connectivity of key regions. As we begin to identify some of the circuits common to the pathophysiology of many of these diseases, we can take advantage of new, minimally invasive, and highly targeted interventions, such as neuromodulation and neural interface technologies, to help treat drug resistant patients with debilitating symptoms but no surgical cure.
We envision a future in which neuroengineering of the brain to alleviate a wide range of neurological symptoms will be possible, without incision, and within either the home or outpatient setting. Patients who do not respond to drug therapies and are not candidates for neurosurgery, with idiopathic disease etiology, will have available minimally invasive neuromodulation therapeutic options. Over time, such options could replace more conventional, invasive surgical procedures. Coupled to minimally invasive neuromodulation methods, there is a need for comfortable, wearable, thin-film electronic sensors to monitor neural activity, so that modulation can be performed in real time and with high responsiveness. Neural interface technologies involved in detection, recording, and processing of signals from brain and integrated analysis of neural signals, powered by machine-learning algorithms, will provide defined outputs relayed to portable devices to provide monitoring ability at home, and effective communication with a care provider.
Project Name: The neuroinflammatory response in the fourth dimension: Creating a neuronal organoid-on-a-chip platform to assess the impact of circadian dysregulation on the immune response to Alzheimer’s disease
PIs: Jonathan Dordick, PhD (RPI), Jennifer Hurley, PhD (RPI), Mariana Figueiro, PhD (Mount Sinai)
Abstract: Chronic circadian disruption (CD), e.g., via shift work, overexposure to light at night, or dim light during the day, can lead to a wide array of negative health effects, including an increase in the risk for, and severity of Alzheimer’s disease andrRelated dementias (Adrds). As Adrd cases are expected to reach more than 150 million worldwide by 2050, the development and improvement of treatment options for Adrd is essential. We hypothesize that circadian rhythms play a pivotal role in the nature and progression of macrophage/microglial responses towards amyloid beta (Aβ), and that by using patient-derived macrophages and neurons, we can address how CD impacts human macrophages at the individual level. To test this hypothesis, we will use animal models to analyze the impact of CD on neuroinflammation and investigate the effect of CD on human entrained and disrupted Adrd patients. A key aspect of this project is to create and exploit a 3D neuronal organoid-on-a-chip platform to assess CD-induced changes on neuronal cell populations and neuroinflammation.
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