Mechanisms of Response to Therapeutic Intervention in Clinical High Risk (CHR) for Psychosis

The MRI and TMS interventions described below will yield measures of change in the targeted brain regions in post- relative to pre- intervention comparisons. These change measures will be compared relative to changes in the sham/control group and the HC group. Furthermore, they will be compared to HC to assess improvement or normalization of brain function in the targeted brain regions. In addition, the investigators will examine treatment effects on traditional biomarkers that are likely to be impacted by such interventions: ERP, NP and NLP measures. Here, mindfulness meditation practiced during a real-time fMRI NFB session will be used to bring connectivity changes to brain structures involved in positive psychiatric symptoms (e.g. attenuated psychotic symptoms) in order to to reduce them.

Individuals with CHR who are randomly assigned to this arm will receive mb-rt-fMRI-NFB, as do the experimental group, but it will be aimed at a motor cortex location that is not part of the prefrontal neural networks targeted in the experimental group.

In previous work, the investigators used a multivariate pattern analysis to identify functional connectivity correlates of negative symptom severity in a schizophrenia (SZ) group. DLPFC-cerebellum hypo-connectivity was strongly correlated with negative symptoms. In a separate SZ cohort, the investigators used rTMS targeting the cerebellum to manipulate this circuit. The rTMS-induced increase in functional connectivity in a cerebellar-midbrain-DLPFC circuit was strongly linked to negative symptom severity reduction. Furthermore, individuals varied in the degree of change in functional connectivity in response to rTMS. This variation strongly predicted variation in post-rTMS symptom severity. The investigators predict that rTMS based intervention, but not sham rTMS, will similarly impact the cerebellar-midbrain-dorsolateral prefrontal cortex (DLPFC) network in the CHR group receiving real but not sham rTMS.

Individuals with CHR who are randomly assigned to this arm will receive rTMS, as do the experimental group, but it will be aimed at a motor cortex location that is not part of the prefrontal neural networks targeted in the experimental group.