2026 ECNP Congress

PS04-4049

Feasibility of a portable hybrid platform for assessing neuroplasticity and cognition during esketamine treatment in therapy-resistant depression

Stefan Vestring — B. Murphy, V. Galuba, H. Kiiski, R. Rea, E. McWilliams, A. Watrous, E. Tunbridge, C. Normann · University Clinic Freiburg, Psychiatry, Freiburg im Breisgau, Germany

2026 ECNP Congress

Introduction

Major depressive disorder (MDD) is associated with impaired neuroplasticity and cognitive deficits, including impairments in executive function, working memory, and processing speed. These deficits contribute substantially to functional impairment and may serve as early indicators of treatment response. Esketamine enhances synaptic plasticity, demonstrated in preclinical models, providing an opportunity to investigate whether neurophysiological plasticity markers relate to functional cognitive improvement in clinical settings. A key translational challenge is the ecological validity of such assessments: most studies rely on single, clinic-based measurements, limiting insight into day-to-day fluctuations in real-world settings. Mobile technologies enabling repeated at-home monitoring offer a promising solution [3,4], yet despite prior demonstrations of feasibility in other clinical populations, evidence for their utility in patients with MDD undergoing clinical care remains limited.

Aims

The PlastiCogMDD study aims to evaluate the feasibility, adherence, and data quality of a multimodal platform (Neulogiq® [5]) for repeated cognitive and neurophysiological assessment in patients with therapy-resistant MDD, and capture the effects of esketamine on neuroplasticity and cognitive performance markers across both home-based or in-clinic settings. Change in VEP-measured (visually evoked potential) plasticity before and after esketamine versus treatment-as-usual (TAU) control group serves as the primary clinical outcome, measured using portable dry electroencephalography (EEG).

Methods

PlastiCogMDD is a single-centre, unblinded, parallel-group study conducted at the University Medical Center Freiburg (N=54). Patients with therapy-resistant MDD are randomised to observation timeframe, not treatment. Group 1 (MDD TAU + esketamine, n=27) is observed during esketamine initiation; Group 2 (MDD TAU, n=27) is assessed during the clinically indicated waiting period prior to esketamine. All patients continue standard antidepressant treatment. The 22-day observation window combines four structured in-clinic visits, including EEG-based assessments (VEP modulation, auditory steady-state response, resting-state EEG), a visual associative memory task and clinical ratings (Montgomery-Åsberg Depression Rating Scale, Beck Depression Inventory) with continuous at-home assessments via a dedicated tablet twice daily. At-home tasks include cognitive tests (Digit Symbol Substitution Test, N-Back Task) and mood ratings (Visual Analogue Scale). Patient-reported platform usability is assessed at end-of-study via System Usability Scale (SUS). This design allows longitudinal tracking of cognitive and neurophysiological parameters across both settings simultaneously.

Results

Recruitment is progressing above the expected rate; final results are anticipated by Q3 2027. Interim analyses show excellent feasibility: over 95% of all scheduled at-home task sessions were completed and yielded analysable data, including accounting for technical issues and patient non-compliance. Patient-reported burden for at-home assessments was minimal, supporting tolerability of the platform in this clinical population. Mean SUS score was >84, indicating good usability. Raw and processed data examples and interim means from both at-home and in-clinic sessions are presented.

Conclusions

These interim results demonstrate that repeated cognitive and neurophysiological assessment using a portable dry EEG platform is highly feasible and well tolerated in patients with therapy-resistant MDD. The randomisation approach enables the effects of esketamine on neuroplasticity and cognitive markers to be captured within a naturalistic clinical context. These findings support the broader utility of wearable EEG technology for longitudinal monitoring in depression research and clinical practice.

References

  1. Normann, C., Schmitz, D., Fürmaier, A., Döing, C., Bach, M., 2007. Long-term plasticity of visually evoked potentials in humans is altered in major depression. Biological psychiatry, 62(5), 373–380.
  2. Nugent, A. C., Ballard, E. D., Gould, T. D., Park, L. T., Moaddel, R., Brutsche, N. E., Zarate, C. A., Jr., 2019. Ketamine has distinct electrophysiological and behavioral effects in depressed and healthy subjects. Molecular psychiatry, 24(7), 1040–1052.
  3. McWilliams, E. C., Barbey, F. M., Dyer, J. F., Islam, M. N., McGuinness, B., Murphy, B., Nolan, H., Passmore, P., Rueda-Delgado, L. M., Buick, A. R., 2021. Feasibility of Repeated Assessment of Cognitive Function in Older Adults Using a Wireless, Mobile, Dry-EEG Headset and Tablet-Based Games. Frontiers in psychiatry, 12, 574482.
  4. Barbey, F. M., Farina, F. R., Buick, A. R., Danyeli, L., Dyer, J. F., Islam, M. N., Krylova, M., Murphy, B., Nolan, H., Rueda-Delgado, L. M., Walter, M., Whelan, R., 2022. Neuroscience from the comfort of your home: Repeated, self-administered wireless dry EEG measures brain function with high fidelity. Frontiers in digital health, 4, 944753.
  5. McWilliams, E. C., Milanovic, S. M., Elvsåshagen, T., Lew, R., Hopkins, S. C., Andrews, C., Walling, D. P., Islam, M. N., Nolan, H., Koblan, K. S., Murphy, B., 2026. A brief visual evoked potential (VEP) modulation assessment of experience-dependent plasticity recorded via wireless dry-EEG headset in Phase 1 clinical units. Scientific reports, 16(1), 620.