Non-invasive brain stimulation increases default mode network functional connectivity in a patient with Posterior Cortical Atrophy

Repetitive transcranial magnetic stimulation (rTMS) has been explored as an intervention in typical amnestic Alzheimer's Disease (AD). However, its effects on episodic and associative memory in atypical forms of AD are less known. Posterior cortical atrophy (PCA) is primarily characterized by visuospatial and visuoperceptual symptoms, although significant episodic memory deficits are often observed. To investigate whether intermittent theta burst (iTBS, a form of rTMS), guided by individualized functional imaging, can modulate functional networks and improve associative memory in a patient with PCA presenting with memory impairments. A stimulation target in the left caudal middle frontal gyrus (cMFG) was selected based on peak functional connectivity with the default mode network (DMN). iTBS was administered to this target in a randomized placebo-controlled paradigm. Primary outcomes were changes in functional connectivity of the stimulation target and associative memory performance. Visuospatial working memory and global cognition were secondary outcomes. Consistent with our hypothesis, active iTBS increased connectivity between the cMFG target and distributed DMN regions. Contrary to our hypothesis, associative memory performance did not improve, but we did observe improvements in visuospatial working memory. This case report supports further controlled clinical trials using functional connectivity guided rTMS in PCA.