Don McLaren Talk Abstract

See below for the Abstract for Don McLaren's talk. As a reminder he will be talking in BO20 at 4pm on the 21st of July. Hope to see you all there. Best, Jonny *The Potential of Functional MRI in Early Phase Clinical Trials: Looking Forward* With promising therapies for Alzheimer’s disease (AD) entering clinical trials, functional magnetic resonance imaging (fMRI) has potential as a biomarker of trait or state to identify individuals who may be at higher risk or who are showing early neurophysiological changes in cognitive networks, and as a biomarker of rate, effect or efficacy to provide an early biological signal to prognosticate, gauge clinical progression or treatment response. The majority of fMRI studies in patients with AD have nevertheless focused on regional task-related activity rather than how functional connectivity during performance of a cognitive task can be related to disease stage, treatment or a clinical outcome measure. The use of fMRI in clinical trials will require a network perspective of brain activity and connectivity. The utilization of fMRI in clinical trials requires: (1) a well-known underlying pathology; (2) a well-validated reliable cognitive paradigm; and (3) sensitive and reliable analysis methodology. Using Alzheimer’s disease an exemplar, I will outline the pathological processes in Alzheimer’s disease. I will describe several paradigms for probing episodic memory, the hallmark symptom in Alzheimer’s disease. Finally, I will discuss different fMRI analysis approaches and how to could be leveraged in clinical trials. In particular, I will focus on using generalized psychophysiological interactions (gPPI) to identify potential candidate networks for cognitive and pharmacological interventions. Nevertheless, it is important to recognize that fMRI will never be the sole determinant in making decisions about to proceed or stop a clinical trial. To that end, I will briefly present some novel ideas about improving sensitivity of cognitive performance measures in longitudinal studies and mention some recent findings in other imaging modalities. I will end with some thoughts about how to integrate multiple modalities. The goal of bringing imaging and other modalities into a clinical trial is reduce the duration and number of subjects in the trial without compromising the science. Ultimately, using fMRI as a complementary approach in clinical trials will improve the throughput.