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Title:
Differential outcomes of rTMS and anesthesia effects on functional
connectivity in the rat brain

Authors & affiliations:
11

1

1

Julia Boonzaier , Geralda A.F. van Tilborg , Milou Straathof , Petar I. Petrov , Caroline L.
1
121van Heijningen , Gerard van Vliet , Nickolay Smirnov , Annette van der Toorn ,1
1Sebastiaan F. Neggers , Rick M. Dijkhuizen
1

University Medical Center Utrecht, The Netherlands
2
Neurosoft, Ivanovo, Russia
J.Boonzaier@umcutrecht.nl

Abstract: (Your abstract must use Normal style and must fit in this box. Your abstract should be nolonger than 300 words. The box will ‘expand’ over 2 pages as you add text/diagrams into it.)

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive
neuromodulation technique routinely used in humans in their awake state. In
contrast, rTMS experiments in rodents are often executed under anesthesia toallow for reproducible and focal stimulation. Effects of rTMS on neural networks
are, however, reliant on underlying brain activity at the time of stimulation, andmay therefore be significantly affected by the anesthetic state. Using lowfrequency rTMS, this study tested whether resting-state functional connectivity
in stimulated cortical tissue is diversely affected by different anesthetics.
Naïve, male Sprague Dawley rats were divided into three experimental groups.
All animals received 20 minutes rTMS (1Hz) for four consecutive days, while
anesthetized with either isoflurane (n=5), dexmedetomidine (n=6) or propofol(n=6). Stimulation was applied over the right sensorimotor cortex, using a 25mm
figure-of-eight coil (Neurosoft Ltd.). Preceding and following rTMS, functional
MRI was performed while animals were anesthetized with separate anesthetics.
Spatiotemporal correlations between low-frequency BOLD fluctuations
representing functional connectivity, were calculated between primary andsecondary motor cortices, primary and secondary somatosensory cortices,thalamus, and caudate putamen. Changes in inter- and intrahemisphericfunctional connectivity were evaluated with a mixed-design ANOVA (RStudioInc.v.0.99.903).
There was a significant effect of anesthesia on functional connectivity between
different inter- and intrahemispheric regions, with generally higher values in
isoflurane-anesthetized animals as compared to dexmedetomidine and propofol
anesthesia. In addition, there was a tendency of lower functional connectivity,
particularly between sensorimotor cortex and thalamus (Fig.1).

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Low-frequency rTMS has the ability to reduce cortical excitability, an effect thatshares similarities with long-term depression. Consequently, this may lead tosignificant changes in functional connectivity within the stimulated network.
Although we observed tendencies for lowered functional connectivity after lowfrequency rTMS, this varied considerably between different anesthetics. Our
results emphasize the importance of considering the effect of anesthesia on theoutcome of experimental rTMS.