Improving cognition in Early Psychosis using Transcranial Magnetic Stimulation

All interventions/exposure are administered face-to-face with the participant. Prior to TMS the participant will have a functional and structural MRI brain scan. The MRI will be overseen by the lead PI, who is a psychiatrist. Assessment of motor cortex excitability using electromyography electrodes on the skin overlying surface muscles of the arm; single pulses of TMS are given to the motor cortex of the participant to induce contraction of muscle in the arm with a motor potential of greater than 200 µV recorded on electromyography. The stimulation intensity required to evoke contraction at the motor potential of greater than 200 µV on at least 3 out of 5 trials is noted. The stimulation intensity to be used for the intervention will be set to 80 percent of the dose necessary to induce muscle contraction at motor potential of greater than 200 µV i.e. the active motor threshold. The assessment of motor cortex excitability will be performed by the co-PI, who is a neuroscientist, the lead PI, who is a psychiatrist, and a trained RA. Active Intervention: A standard intermittent theta burst stimulation (iTBS) protocol will be used to induce local changes in cortical activity at the left and right dorsolateral prefrontal cortex (in that order), interleaved by 60 minutes between left and right target sites. The iTBS uses a stimulation pattern in which 3 pulses of stimulation are given at 50 Hz, repeated at 5 Hz for 2 secs, with a total of 600 total train pulses at 80 percent of active motor threshold. This dose will be delivered to each site in a single session (interleaved 60 minutes between doses) on one day only. During the interleaved 60 minute period the participant will be required to remain in a quiet room. A trained RA will administer questionnaires (e.g. adverse event log) and take the participant through the tasks that will be undertaken in the MRI. The active intervention will be performed by the co-PI, who is a neuroscientist, the lead PI, who is a psychiatrist, and a trained RA. Placebo Intervention: Placebo stimulation will be administered with a specific coil that is made by the same manufacturer. This coil mimics the noise and effects on the scalp muscles of the real TMS but does not affect the neural activity of the targeted area. The placebo intervention will be performed by the co-PI, who is a neuroscientist, the lead PI, who is a psychiatrist, and a trained RA. Orientation of brain region target for active and placebo intervention is performed using neuro-navigation software and hardware called visor2 (https://www.ant-neuro.com/products/visor2). The visor 2 system uses the participant’s structural MRI scan to personalise the targeting of TMS to the individual’s unique brain anatomy. The orientation of brain region target for active and placebo intervention will be performed the co-PI, who is a neuroscientist, the lead PI, who is a psychiatrist, and a trained RA. The participant will undergo two post-intervention assessments. The participant will complete an adverse event log during (within 60 mins of first TMS) and after TMS dosing (within 60 mins of second TMS and up to 1 week after second TMS). The participant will complete an MRI brain scan within 60 minutes after second TMS dosing so as to measure the functional brain changes that occur as a result of intervention. Both these post-intervention assessments will be overseen by the lead PI, who is a psychiatrist.