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.
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