2026 ECNP Congress

PS04-4184

The effect of slMFB DBS in depression and OCD on reaction time in a monetary incentive delay task

Dora M. Meyer-Doll — M. Heinrichs, V.A. Coenen, C. Normann, D. Endres, J. Weiser, M. Czornik, J.C. Baldermann-Weiß, T.E. Schlaepfer · Medical Center - University of Freiburg, Department of Psychiatry and Psychotherapy, Freiburg im Breisgau, Germany

2026 ECNP Congress

Background

Reward processing in depression and obsessive-compulsive disorder (OCD) differs from healthy controls [1,2]. Given its structural and functional role in neural reward processing, the superolateral medial forebrain bundle (slMFB) has been identified as target for deep brain stimulation (DBS) in treatment-resistant depression (TRD) and severe, chronic OCD. The hypothesized mode of action is a normalization of the neural activity of the reward network [3, 4, 5], but has not yet been explored systematically in human samples.

Aims

The exploratory study DeCompReS (Depression, Obsessive Compulsive Disorder, Reward Processing and the influence of Deep Brain Stimulation, DRKS00024593) aimed to: (1) examine behavioral indicators of reward processing across depression, OCD, and healthy controls; and (2) assess the acute impact of slMFB DBS (stimulation ON vs. OFF) on these indicators.

Methods

We included 86 participants: TRD with treatment-as-usual (TAU) (n=20), OCD TAU (n=20), healthy controls (n=20), TRD with slMFB DBS (n=16), and OCD with slMFB DBS (n=10). All completed a test battery including a Monetary Incentive Delay Task (MIDT) that used the conditions win, loss and neutral. Depending on their reaction time, participants could earn up to 20€ during the task. Patients with slMFB DBS temporarily deactivated stimulation, repeating the MIDT with a balanced ON-OFF/OFF-ON sequence. Primary outcomes were log reaction times (RTs) as indicators of reward motivated behavior. For analysis, we conducted two separate linear mixed models, one for patients with slMFB DBS (DBS model, 1488 observations) and one for participants without DBS (nonDBS model, 1748 observations). These assessed the effects of task condition, symptom severity (depression and OCD scores) and stimulation status (only in case of slMFB DBS) on log reaction times.

Results

As expected, participants responded faster during win and loss conditions versus neutral (p < 0.01). Higher OCD severity scores predicted lower log RTs in both the DBS model (β (SE) = -0.014 (0.006), p < 0.05, 95% CI = [-0.026, -0.002]) and the nonDBS model (β (SE) = -0.006 (0.003), p < 0.05, 95% CI = [-0.011, 0]). In participants without DBS, higher depression severity predicted higher log RTs (β (SE) = 0.008 (0.003),p < 0.05, 95% CI = [0.001, 0.014]). In patients with slMFB DBS, stimulation ON decreased the log RTs in the win condition (β (SE) = -0.101 (0.04), p < 0.05, 95% CI = [-0.024, -0.179]).

Conclusions

The intended manipulation of the reaction times by task condition was successful in participants with and without DBS. “OCD speeding” was present across groups and might possibly be driven by punishment avoidance. “Depressive slowing” was present in patients without DBS, but was not observed in patients with slMFB DBS. Crucially, turning off slMFB DBS slowed the behavioral response to reward anticipation. This observation supports the hypothesized mode of action of slMFB DBS, that proposes a normalization in reward processing.

References

  1. Huey, E. D., Zahn, R., Krueger, F., Moll, J., Kapogiannis, D., Wassermann, E. M., & Grafman, J. (2008). A psychological and neuroanatomical model of obsessive-compulsive disorder. The Journal of neuropsychiatry and clinical neurosciences, 20(4), 390–408.
  2. Huys, Q. J., Pizzagalli, D. A., Bogdan, R., & Dayan, P. (2013). Mapping anhedonia onto reinforcement learning: a behavioural meta-analysis. Biology of mood & anxiety disorders, 3(1), 12.
  3. Coenen, V. A., Schlaepfer, T. E., Goll, P., Reinacher, P. C., Voderholzer, U., Tebartz van Elst, L., . . . Freyer, T. (2017). The medial forebrain bundle as a target for deep brain stimulation for obsessive-compulsive disorder. CNS Spectrums, 22(3), 8. doi:10.1017/S1092852916000286
  4. Coenen, V. A., Schlaepfer, T. E., Sajonz, B. E. A., Reinacher, P. C., Döbrössy, M. D., & Reisert, M. (2022). “The Heart Asks Pleasure First”—Conceptualizing Psychiatric Diseases as MAINTENANCE Network Dysfunctions through Insights from slMFB DBS in Depression and Obsessive–Compulsive Disorder. Brain Sciences, 12(4), 438.
  5. Schlaepfer, T. E., Bewernick, B. H., Kayser, S., Hurlemann, R., & Coenen, V. A. (2014). Deep brain stimulation of the human reward system for major depression—rationale, outcomes and outlook. Neuropsychopharmacology, 39(6), 1303–1314. doi:10.1038/npp.2014.28