Self-control and motivation in addictions

Harmful alcohol use is one of the most pressing public health issues internationally. In the United Kingdom, alcohol misuse represents 10% of the burden of disease and death costing in excess of £21 billion per year. Despite this, these disorders remain poorly treated emphasizing the urgent need to develop novel therapeutic approaches. This proposal aims to understand the interaction between impulsivity and motivation, processes fundamental to regulating behavior and crucial to understanding the risk for and relapse in addictions. Impulsivity or self-control is the tendency towards rapid poorly considered decisions or the inability to stop actions. There are multiple types of impulsivity. Here I focus on a specific form known as waiting impulsivity, or the tendency to act too early. Waiting impulsivity has robust evidence in animal studies for an association with addictions, and is less well understood in humans. I propose that waiting impulsivity in humans involves two processes: voluntary stopping and motivation. Voluntary stopping involves the internal decision to stop. Motivation involves the role of rewards to influence actions or energize behavior. I use a novel task and multiple innovative techniques to understand this relationship between voluntary stopping and motivation and the relationship between prefrontal cortical brain regions and the basal ganglia. I then develop an intervention based on these processes to train voluntary self-control in alcohol use disorders paired with stimulation of the underlying brain network. Finally I extend this to a population level and ask how these processes along with other factors predict alcohol misuse. Together these studies emphasize a testable theory-driven model of waiting impulsivity with immediate translational treatment for addictions.

Harmful alcohol use is a major international public health issue. It remains poorly treated emphasizing the need for novel therapeutic approaches. Understanding the interaction of self-control and motivation is crucial to the capacity to regulate behavior and to the risk for and relapse underlying substance use disorders. Impulsivity or self-control is a heterogeneous construct with multiple subtypes. Waiting impulsivity, a subtype of impulsivity, characterized by anticipatory early responses, has a robust preclinical history and association with addictions but is poorly understood in humans. Waiting impulsivity itself is comprised of multiple components. Here I propose a model of waiting impulsivity involving intentional inhibition and motivation mediated by opponent dorsomedial and ventral prefrontal processes. Intentional inhibition is a uniquely human construct involving the inhibition of responding based on internal and voluntary processes which are likely highly relevant to the real world self-control of addictions. I use a novel task developed in my group and multimodal techniques in healthy controls to interrogate the underlying neural architecture of intentional inhibition and motivation. I then uniquely capitalize on patient populations who have undergone deep brain stimulation to allow direct modulation and dissociation of these relevant networks to understand the underlying cognitive neuroanatomy. I then test a mechanistically-informed intervention for alcohol use disorders combining a behavioural intervention to train self-control and non-invasive neuromodulation to enhance network activity. Finally, I seek to contextualize these measures at the population neuroscience level and ask how these factors predict addiction behaviours on a data-driven dimensional population level. Together these studies emphasize a testable theory-driven neurobiologically coherent model of waiting impulsivity with immediate translational treatment for addictions.

Potential beneficiaries of this proposal include academic researchers, clinicians, government and non-government organizations and charities and patient support groups involved in optimizing the recognition and treatment of addictions. The research output from understanding the basic neuroscience of intentional inhibition and motivation will benefit academic researchers. The research output from the intervention and population-level predictors will benefit academic researchers, clinicians and organizations and patient support groups. The intervention, if successful, can be adapted to an accessible online task that can be disseminated on a much wider basis. The use of pharmacological management for the treatment of addictions, while effective in therapeutic trials, has not translated into widespread use. The development of novel non-pharmacological therapeutic strategies that isolate specific behavioural interventions and seek to optimize the underlying neural network using a safe non-interventional technique may be more likely to be utilized. This research, along with other research on behavioural intervention training, should if effective, potentially lead to changes in therapeutic guidelines for addictions. Understanding predictors for alcohol misuse can lead to the development of algorithmic predictors to early identification of those at risk for alcohol misuse leading to earlier interventions. Were the development of such an algorithm possible, this could lead to important public health policies and benefits.

The researchers on the project will acquire skills in optimizing task development, imaging and neuromodulation skills, recruitment and interactions with patient population, management of clinical research and advanced statistical techniques.