Temporal dynamics of intranasal oxytocin in human brain electrophysiology

Abstract

Oxytocin (OT) is a key modulator of human social cognition, popular in behavioral neuroscience. To adequately design and interpret intranasal OT (IN-OT) research, it is crucial to know for how long it affects human brain function once administered. However, this has been mostly deduced from peripheral body fluids studies, or uncommonly used dosages. We aimed to characterize IN-OT’s effects on human brain function using resting-state EEG microstates across a typical experimental session duration. Nineteen healthy males participated in a double-blind, placebo-controlled, within-subject, cross-over design of 24 IU of IN-OT in 12-min windows 15 min-to-1 h 42min after administration. We observed IN-OT effects on all microstates, across the observation span. During eyes-closed, IN-OT increased duration and contribution of A and contribution and occurrence of D, decreased duration and contribution of B and C; and increased transition probability C-to-B and C-to-D. In eyes-open, it increased A-to-C and A-to-D. As microstates A and D have been related to phonological auditory and attentional networks, respectively, we posit IN-OT may tune the brain for reception of external stimuli, particularly of social nature—tentatively supporting current neurocognitive hypotheses of OT. Moreover, we contrast our overall results against a comprehensive literature review of IN-OT time-course effects in the brain, highlighting comparability issues.

Sniffing oxytocin: Nose to brain or nose to blood?

“…Of note, while the enhancement effect of OXT on delta-beta low CFC occurred from Rest 3 to 6 (i.e., 30-75 min post-treatment) and was strongest in Rest 4 (i.e., 45 min post-treatment) compared to the other two groups, its effects on delta-beta high CFC were exclusively restricted to Rest 4. These time courses for rsEEG effects of intranasal OXT are very similar to those previously reported for changes in EEG microstate features [ 35 ] and regional cerebral blood flow changes [ 27 , 48 ]. However, our findings are inconsistent with a previous study reporting that intranasal OXT decreased delta-beta CFC [ 37 ].…”

“…While previous studies have tended to focus on either task-based or resting-state fMRI responses to OXT [ 2 , 3 , 33 ], going forward, and to facilitate simultaneous blood sampling and taking physiological measures, another option is to capitalize on resting-state electroencephalography (rsEEG). To date, relatively few studies have studied effects of intranasal OXT on rsEEG with some evidence for effects on microstates [ 34 , 35 ]. Other promising candidates are measures of neural synchronization between alpha and theta rhythms [ 36 ] and also altered delta-beta cross frequency coupling (CFC) [ 37 ].…”

Temporal profile of intranasal oxytocin in the human autonomic nervous system at rest: An electrocardiography and pupillometry study

“…Naturally, for pupil size, the analysis was only performed for the eyes-open condition. Regarding the mood scales, we have reported on the same analysis earlier in a sample differing in one subject (Zelenina et al, 2022). LMMs are suitable for datasets with missing data and inter-individual random differences (Meteyard and Davies, 2020) and allow for the inclusion of covariates of no interest that vary within subjects.…”

“…However, there is, thus far, inconsistency in findings, variability in the methods and in the outcomes and response biomarkers measured ( Winterton et al, 2021 ), with insufficient metanalytical evidence of improvement in clinical populations ( Huang et al, 2021 ; Sabe et al, 2021 ). Intranasal OT (IN-OT) is, by far, the most frequent route of OT administration in human neuroscience studies, and we have recently summarized these studies ( Zelenina et al, 2022 ). Overall, IN-OT’s temporal profile (i.e., across a typical neuroscience experimental session time) at rest has been characterized by OT measurement in peripheral fluids (i.e., blood plasma, saliva and urine) and central nervous system OT measurements (i.e., in cerebral spinal fluid) or activity (via blood oxygen level-dependent activation using magnetic resonance imaging (MRI), and, by us, microstates using electroencephalography (EEG) ( Zelenina et al, 2022 ).…”

“…Intranasal OT (IN-OT) is, by far, the most frequent route of OT administration in human neuroscience studies, and we have recently summarized these studies ( Zelenina et al, 2022 ). Overall, IN-OT’s temporal profile (i.e., across a typical neuroscience experimental session time) at rest has been characterized by OT measurement in peripheral fluids (i.e., blood plasma, saliva and urine) and central nervous system OT measurements (i.e., in cerebral spinal fluid) or activity (via blood oxygen level-dependent activation using magnetic resonance imaging (MRI), and, by us, microstates using electroencephalography (EEG) ( Zelenina et al, 2022 ). However, to the best of our knowledge, the temporal profile of IN-OT is still unexamined in the peripheral nervous system at rest.…”