Non-invasive Neuromodulation Targeting Approach by Mapping Stimulations and Lesions That Modify Visual Memory

Therapeutic brain stimulation is believed to target specific networks, but targeting approaches for memory remain debated. For other symptoms, neuromodulation targets have been localized by mapping connectivity of lesions and stimulation sites to specific symptoms. This approach has yielded networks for global memory, but it remains unclear whether it applies to specific types of memory. Here, we mapped connectivity of stimulation sites, lesions, and atrophy patterns associated with different memory types. We included 544 individuals across three datasets: transcranial magnetic stimulation (N=262), penetrating head trauma (N=169), and ischemic stroke (N=113). We identified a network preferentially connected to lesions and stimulation sites specifically associated with changes in visual memory. Of note, the direction of this effect was inverted depending on whether lesions or stimulation occurred at younger age or an older age, consistent with prior results. This age effect was replicated in an independent dataset of patients with preclinical Alzheimer's disease (N=1240). To examine neuromodulation targets, we computed electrical field models for potential TMS sites that overlap with the networks derived from each stimulation or lesion dataset; the resulting targets intersected with established targets that demonstrated efficacy for treating memory impairment - precuneus, cortical-hippocampal network, and dorsolateral prefrontal cortex - with peak intersection at medial posterior parietal lobe, angular gyrus, and left anterior middle frontal gyrus, respectively. Future head-to-head clinical trials are needed to systematically compare these proposed neuromodulation targets against each other.