Network-based neuromodulation for posterior cortical atrophy

University Of Michigan At Ann Arbor, Ann Arbor MI

Investigators

Abstract

Abstract This is the first study to evaluate the effects of personalized brain stimulation as a potential treatment for those with posterior cortical atrophy (PCA), a condition that is most often caused by Alzheimer’s disease (AD). Individuals with PCA generally have intact vision but, as pathology spreads through the brain, have increasing difficulty “making sense” of what they see. Examples of this visuospatial impairment include difficulty locating objects in crowded environments (e.g., locating items in a full refrigerator) or traveling from one location to another (i.e., spatial navigation). Both recent findings in the literature and our preliminary data suggest that the Dorsal Attention Network (DAN) is affected early in the course of PCA, which means that treatments targeting this network may be able to improve functioning in everyday life. We test this possibility by providing personalized brain stimulation for those with PCA. Specifically, we will use each participant’s functional magnetic resonance imaging (fMRI) brain scans to identify the DAN and measure how well it is functioning relative to other brain networks. We will then develop a personalized high-definition transcranial direct current stimulation (HD-tDCS) montage that delivers electrical current to key regions of the DAN, ensuring they are aligned with the participant’s fluorodeoxyglucose (FDG) positron emission tomography (PET) scan. Importantly, our novel methods allow us to equate the the amount of electricity delivered to the DAN for each participant, thereby markedly reducing the variability seen with traditional one-size-fits all brain stimulation approaches. Using a double blind randomized controlled trial format (i.e., active vs. sham), we will evaluate HD-tDCS induced changes in the DAN using fMRI and a combination of tasks that reflect real-world performance. For example, we will use using eye-tracking to evaluate participants’ ability to identify objects in crowded environments as well as an innovative immersive virtual reality (iVR) spatial navigation paradigm. Moreover, we will use functional near infrared spectroscopy (fNIRS) to evaluate changes in brain activity during this spatial navigation task. Importantly, we will evaluate these changes after relatively brief (i.e., 8 session Randomized Controlled Trial) and a subsequent open-label 6-month period of HD-tDCS. The extended duration is possible thanks to our first-of-its-kind personalized 3D- printed headgear and validated training program that teaches informants to administer HD-tDCS remotely as we supervise through videoconference. The open-label format allows us to refine methods and determine optimal treatment parameters necessary for a subsequent large-scale trial. Finally, we will perform exploratory analyses to identify participant-level factors associated with treatment response in order to refine a subsequent late-stage clinical trial. Our approach builds on decades of efforts to enhance early detection of AD pathology in vivo by translating this knowledge into personalized treatment protocols that target dysfunctional networks. Our plans to explore response heterogeneity will further promote precision brain stimulation for those with PCA and, ultimately, other neurodegenerative conditions in subsequent Phase II/III trials.