4 - (SYM 66) the Ventromedial Prefrontal Cortex as a Potential Target to Enhance Hope for Individuals with Suicidal Thoughts and Behaviors

Background: Hopelessness is a cardinal symptom associated with suicide and involves reduced expectation of positive future outcomes. Those at high suicide risk show less specificity and positivity during episodic future thinking (EFT). EFT involves activation of a prefrontal-temporal-parietal network centered on the ventromedial PFC (vmPFC). We describe two functional MRI studies examining (1) brain activation during EFT for individuals with MDD and prior suicide attempts and current ideation (high suicide risk [MDD+SR]) and (2) feasibility of fMRI-based vmPFC neurofeedback (vmPFC rtfMRI-nf) during positive future thinking for individuals with current suicidal intent or plan (MDD+SI).

Methods: Study 1 included 30 individuals with MDD, 15 with MDD+SR. During fMRI, participants were prompted to imagine personally-relevant positive, negative, and neutral future events (15 sec blocks; 8 blocks/valence) and rate the vividness of each. Group by condition interaction effects were estimated using a whole-brain linear mixed model (p< .005, Monte Carlo corrected). Study 2 included six individuals with MDD+SI. Each of three rtfMRI-nf runs rotated between 40-sec “Rest”, “Count,” or “Imagine” blocks. For the latter, participants imagined personally-relevant future positive events while upregulating vmPFC activity, represented by the height of a red bar. At the end, there was a “Transfer” run in which no neurofeedback was provided.

Results: For Study 1, the MDD+SR group reporting higher vividness for negative and lower vividness for positive events (η²=.07) and exhibited less activation in the vmPFC across “Imagine” conditions compared to “Rest” (76 vox, x,y,z=7,45,-11). In Study 2, a vmPFC linear signal increase was observed, including a 56% increase from the first neurofeedback run to transfer. Participants rated the neurofeedback session as challenging (M=6.17 on 1-10 scale) but reported high success in modulating brain activity (M=6.33) and indicated the session would be moderately to extremely (M=7.2) helpful in their mental health treatment.

Conclusions: Study 1 results suggest suicide risk may relate to reduced vividness for positive future events and reduced vmPFC engagement during EFT, regardless of valence. Study 2 provides initial evidence of feasibility and potential utility of vmPFC rtfMRI-nf training for individuals with suicidal thoughts. Future research is needed to identify relationships to clinical outcomes and develop optimal strategies for enhancing positive future thinking.