Noninvasive Neuromodulation and Neuroimaging to Enhance Glymphatic Function for Neurodegenerative and Autoimmune Disorders in Next-Generation Personalized Treatments and Precision Neuropsychiatry: A Perspective Proposal

Transcranial magnetic stimulation-electroencephalography (TMS–EEG) biomarkers have recently become available as a means to obtain new understanding of the causal chains of neuronal signaling in the brain. This is a key piece in the puzzle of how the brain is organized and how it works. Using dMRI tractography, we can map the circuit beneath a chosen cortical target; TMS can then stimulate it, and EEG records responses that reflect—and may even be caused by—activity in that structural circuit. The chain of events after stimulus delivery can be observed and quantified using current neuroimaging and TMS–EEG technology, a matter of tremendous relevance on how to approach novel therapeutic approaches in clinical conditions. Herein, we elaborate upon a perspective of how groundbreaking multi-locus TMS (mTMS) technology associated with EEG and multimodal neuroimaging can be applied to modulate the flow dynamics of the glymphatic system (GS). The enhancement of the GS waste clearance functionality has been shown to improve significantly symptom severity in neurodegenerative disorders such as Alzheimer’s (AD) and Parkinson’s disease (PD) or long COVID. In this perspective paper, we consider that next-generation therapeutics using versatile technologies such as noninvasive neuromodulation and neuroimaging will provide important benefits in public health and in how society can address the management of these difficult-to-deal-with ailments more effectively.