The Effects of Transcutaneous Vagus Nerve Stimulation on Functional Connectivity Within Semantic and Hippocampal Networks in Mild Cognitive Impairment

• Published in: Neurotherapeutics Vol. 20; no. 2; pp. 419 - 430
• Main Authors: Murphy, Aidan J., O’Neal, Alexandria G., Cohen, Ronald A., Lamb, Damon G., Porges, Eric C., Bottari, Sarah A., Ho, Brian, Trifilio, Erin, DeKosky, Steven T., Heilman, Kenneth M., Williamson, John B.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.03.2023; Springer Nature B.V
• Subjects: Alzheimer's disease; Biomedical and Life Sciences; Biomedicine; Brain - diagnostic imaging; Brain mapping; Cognitive ability; Cognitive Dysfunction - therapy; Dementia disorders; Ear; Female; Functional magnetic resonance imaging; Hippocampus; Humans; Locus coeruleus; Magnetic Resonance Imaging; Neural networks; Neurobiology; Neurodegenerative diseases; Neuroimaging; Neurology; Neurosciences; Neurosurgery; Norepinephrine; Original; Original Article; Patients; Semantics; Sensory neurons; Tau protein; Vagus nerve; Vagus Nerve - physiology; Vagus Nerve Stimulation - methods; Functional connectivity; Resting state fMRI; Transcutaneous vagus nerve stimulation (tVNS); Alzheimers disease; Mild cognitive impairment (MCI); Semantic network
• ISSN: 1933-7213; 1878-7479; 1878-7479
• DOI: 10.1007/s13311-022-01318-4

Better treatments are needed to improve cognition and brain health in people with mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Transcutaneous vagus nerve stimulation (tVNS) may impact brain networks relevant to AD through multiple mechanisms including, but not limited to, projection to the locus coeruleus, the brain’s primary source of norepinephrine, and reduction in inflammation. Neuropathological data suggest that the locus coeruleus may be an early site of tau pathology in AD. Thus, tVNS may modify the activity of networks that are impaired and progressively deteriorate in patients with MCI and AD. Fifty patients with MCI (28 women) confirmed via diagnostic consensus conference prior to MRI (sources of info: Montreal Cognitive Assessment Test (MOCA), Clinical Dementia Rating scale (CDR), Functional Activities Questionnaire (FAQ), Hopkins Verbal Learning Test — Revised (HVLT-R) and medical record review) underwent resting state functional magnetic resonance imaging (fMRI) on a Siemens 3 T scanner during tVNS (left tragus, n  = 25) or sham control conditions (left ear lobe, n  = 25). During unilateral left tVNS, compared with ear lobe stimulation, patients with MCI showed alterations in functional connectivity between regions of the brain that are important in semantic and salience functions including regions of the temporal and parietal lobes. Furthermore, connectivity from hippocampi to several cortical and subcortical clusters of ROIs also demonstrated change with tVNS compared with ear lobe stimulation. In conclusion, tVNS modified the activity of brain networks in which disruption correlates with deterioration in AD. These findings suggest afferent target engagement of tVNS, which carries implications for the development of noninvasive therapeutic intervention in the MCI population.