FV 8. The effect of repeated blocks of intermittant theta burst stimulation (iTBS) over the dorsolateral prefrontal cortex (dlPFC) on fronto-striatal connectivity. A 18F-DesmethoxyFallypride (DMFP) Positron Emission Tomography study (PET)

Background. Frontostriatal networks are neural pathways formed between frontal lobe regions and striatum that is involved in cognitive and behavioural processes. Transcranial Magnetic Stimulation (TMS) is able to modulate connectivity in the human brain and it is widely used for clinical purposes to treat depression patients. This exploratory PET and TMS multimodal study would contribute to better understand the role of striatal dopaminergic neurotransmission in the fronto-striatal area.Objective. The main objective of the study is to investigate the fronto-striatal connectivity by measuring the release of dopamine in the striatum in response to an excitatory intermittent theta burst stimulation (iTBS) of the left-dlPFC. APETmeasurement was performed by using the18F-DesmethoxyFallypride (DMFP)radioligand,that is a high affinityreceptor-antagonist which competes with endogenous Dopamine neurotransmitters for D2/D3 receptor binding.Methods. The study was conducted on 23 healthy participants, who underwent iTBS sham (control) and verum stimulations on separate days. The PET scan lasted 120 mins, consisting of 4 iTBS stimulations delivered to the left-DLPFC at 30 mins interval. In verum stimulation, 90% of resting motor threshold (rMT) was used as the stimulation intensity.The excitatory iTBS protocol is delivered in a sequence of trains (burst of 10 pulses in 2 secs having inter train interval of 8 secs), with a total duration of 190 secs. PET dynamic data was analysed using reference region method in which cerebellum was used as the reference region (due to lack of D2-D3 receptors). Binding Potentials (BP) are the main outcome measure representing the ligand binding which is inversely proportional to the Dopamine (DA) levels.Mean Binding Potentials in the sub-regions of the striatum (Nucleus Caudate and Putamen) were compared between the sham and verum stimulation using analysis of variance (ANOVA).Results. iTBS stimulation of the left DLPFC increased thedopamine release (as reflected by BPs) in the striatum areas (putamen and nucleus caudate) in the verum stimulation, as compared to sham stimulation.Although the increase in dopamine release did not differ between the first block of stimulation, we observed significant increase after two, three and fourth blocks of stimulation.Conclusion. Our data suggest that the efficiency of iTBS protocol can effectively enhance fronto-striatal connectivity by applying a higher number of stimuli (i.e., 3rd & 4th TMS block but not 1st-& 2nd block). This minimal time stimulation protocol can be used as a therapy for treating Depression patients by presenting it in the repeated blocks of short intervals. This scheme could prevent the long stimulation protocols, and be less painful.Fig. 1. Figure represents the statistically significant main effect of TMS. The verum stimulation shows a reduction of 8.6% [18F]DMFP Binding Potential as compared to the sham stimulation.Fig. 2. Percentage reduction in [18F] desmethoxyfallypride-binding potentials extracted from the difference of sham and verum stimulation in healthy subjects. Dose-dependent iTBS aftereffects seem to be more pronounced at 3rd block and 4th block respectively as compared to 1st and 2nd block of TMS.