Executive Summary : | Impulsivity is a behavioral defect where an action is taken hastily without foresight, often unnecessarily risky and inappropriate. This tendency is associated with neuropsychiatric disorders such as addiction, bipolar disorder, obsessive compulsive disorder (OCD), conduct disorder, and personality disorders. The major neural center involved in controlling impulsive behavior is the nucleus accumbens (NAc), which is the major component of ventral striatum. NAc is involved in decision making and reward-related behavior. Neuromodulation refers to the alteration of nerve activity through targeted delivery of a stimulus, such as electrical stimulation or chemical agents, to specific neurological sites in the body. Deep brain stimulation (DBS) is a highly effective neuromodulation technique, but it is an invasive technique with low success rates and surgical complications. Non-invasive techniques like transcranial electrical stimulation (tES), transcranial magnetic stimulation (TMS), and focused ultrasound (FUS) are being researched for their ability to influence deep brain structures like NAc. NAc is a potential target for the treatment of pathological impulsive behavior, and medium spiny projection (MSP) neurons are the principal neurons of NAc. It is possible to study the effects of ultrasonic stimulation of NAc and its behavioral manifestations using computational models of MSP neurons. This project aims to develop computational models of NAc neurons in healthy and disease conditions and explore the effects of ultrasonic stimulation. The project aims to study the transient changes in the activity of NAc-H neurons as a result of ultrasonic stimulation, observe short term and long term changes in the activity of NAc-H neurons, and study the transient short term and long term effects on NAc-D neurons as a result of ultrasonic stimulation and explore the implications of these changes on pathological impulsive behavior. There is immense scope and relevance for this project to be commenced in India, as there is no single work reported from India that addresses this important research problem. The project will involve constructing a biophysically detailed model of the NAc-H neuron, incorporating synaptic plasticity, and predicting variations in impulsive behavior based on the variations in the electrical activities of NAc-H neurons. A variant of NAc-H model called NAc-D will be constructed, and the biophysical behavior of the NAc-D in the presence of ultrasound stimulation will be compared with the normal activity of a NAc neuron. The study aims to identify the optimal parameters for ultrasonic stimulation to treat pathological impulsive behavior. The study will also investigate the unfavorable behavioral implications of the variation in neuronal activity of NAc-H and NAc-D neurons caused by ultrasound stimulation. The expected outcome is a detailed understanding of the changes in biophysics and excitability of normal and abnormal NAc neurons elicited by ultrasound stimulation. This study will provide insights into whether and how pathological impulsive behavior can be controlled using ultrasonic stimulation. The findings from the study will help design and develop ultrasonic neuromodulation systems that can be used for the treatment of disorders such as addiction, OCD, and bipolar disorder.
References include studies on the effects of selective lesions of the nucleus accumbens core or shell on inhibitory control and amphetamine-induced impulsive behavior. Ultrasound modulates ion channel currents and induces behavioral avoidance through noninvasive ultrasound deep brain stimulation of the nucleus accumbens. Deep brain stimulation of the nucleus accumbens core affects trait impulsivity in a baseline-dependent manner. The study also explores the evolution in the treatment of psychiatric disorders from psychosurgery to psychopharmacology to neuromodulation. The study also investigates the mechanobiology of brain function and the potential of ultrasound in exciting neurons via mechanosensitive calcium accumulation and ion channel amplification. Overall, the findings from this study will help improve the treatment of various disorders, including addiction, OCD, and bipolar disorder. |