Background Impulsivity describes the tendency to make risky and unplanned decisions, to pick immediate reward over a bigger reward after a period or to not be able to resist the urge to do something. Empathy refers to the ability to be sensitive to and vicariously experience other people's feelings and to create working models of emotional states. Recent neuroscientific research have found that the left frontal part of the brain (left dorsal lateral frontal cortex, RDLPFC) is important in the control of impulsive behaviour and empathy. Self-report questionnaires have been proven valid measures at assessing impulsivity and empathy. Repetitive Transcranial Magnetic Stimulation (rTMS) is a widely used non-invasive brain stimulation procedure; stimulation can be applied at different brain regions depending on the administration method. It temporally changes the way that this part of the brain functions, providing us a further understanding of how this part works. Recent research has found that rTMS on the LDLPFC changes performance based tasks measuring different types of impulsivity and empathy. This study aims to investigate this further to look at the LDLPFC stimulation using the newer form of high-frequency rTMS, intermittent theta burst stimulation (iTBS) and its effects on empathy and two different types of impulsivity. Of interest is also how innate impulsive personality type and empathy trait relate to performance on these tasks.

Aims The specific purposes of this study are to (i) examine whether iTBS is an effective technique for modulating impulsivity and empathy, and to (ii) examine the relationship between the modulatory effects of the iTBS and baseline self-reported impulsivity and empathy.

The key objectives of this study are to examine whether the specific iTBS protocol at RDLPFC can effectively modulate two subtypes of impulsivity (delayed discounting and reflection impulsivity) and empathy, and to examine whether the participant's baseline self-reported impulsivity and empathy scores mediate the modulatory effects of the iTBS on impulsivity and empathy respectively in normal healthy young adults. The secondary objectives of this study are to examine whether the self-reported measures of impulsivity and empathy correlate with their performance-based counterparts.

Experimental protocol and methods The proposed study will be a single-centre, crossover design study, taking place at Queens Medical Centre, Nottinghamshire NHS Trust. Participants (male students or staff) will be recruited from the University of Nottingham. A potential participant will be asked to complete the TMS screening questionnaire to ensure that there are no contraindications to using TMS. After the written informed consent is obtained, he will then be asked to complete an online questionnaire (Barratt Impulsiveness Scale -version 11, BIS-11) measuring self-report impulsivity. The scores obtained from BIS-11 will be one of the screening criteria. If the potential participant is eligible for taking part in the study, he will be invited to the two laboratory sessions. He will then be asked to perform three computerised tasks assessing impulsivity and empathy before and after the iTBS administration. Each session of iTBS will apply 600 pulses to the LDLPFC, with 20 2-second trains and an 8-second inter-train interval for a total stimulation time of 190 seconds. Sham iTBS condition will be administered with the same methodology used for active iTBS condition with a sham coil mimicking noises and vibrations without delivery of magnetic pulses. Participants will be asked to guess which rTMS condition is real after completing the whole study to ascertain that whether the sham manipulation is successful or not. Participants will be monitored if they experience any adverse events during the rTMS session and instructed to report any experience of adverse events after each rTMS session. Tolerability will be presented as the number of reported adverse events and the number of dropouts due to adverse events.

Measurable end points/statistical power of the study To detect the change in impulsivity and empathy resulted from the iTBS intervention, G\*Power 3.1.9.2 was used to estimate sample size required in consideration of interaction effect (impulsivity group × iTBS conditions) of repeated measure ANOVA. The following parameters were selected: effect size f = 0.20 (equivalent to d = 0.40, estimated from the results of previous meta-analyses), alpha error probability = .05, power = (1- β error probability) = .80, number of groups = 2, number of measurements = 2 and correlation among repeated measurements = 0.6. A minimum of total sample size of 42 subjects will be required. Considering the dropout rate of 0.20 (according to previous rTMS studies), 54 subjects will be required for the study, including 27 high impulsivity participants and 27 low impulsivity participants.