AI-Driven Neural Surrogates for In Silico Design of Cognitive-Affective Neuromodulation Targets
Marco Rothermel, Madleen Stenger, Soroush Daftarian, Svenja Jule Francke, Bita Shariatpanahi, José C. García Alanis, Mohammad-Ali Nikouei Mahani, Stefan G. Hofmann, Tim Hahn, Hamidreza Jamalabadi
Abstract
In neuropsychiatry, the primary goal is often not only to decode brain activity but to change it, for example to lessen a negative affective bias or an overly salient memory. Motivated by control theory, we develop an AI-driven neural-surrogate framework that proposes candidate representational changes and tests their predicted perceptual effects from snapshots of stimulus-evoked fMRI activity, without physical stimulation. The framework combines fMRI decoding, deep generative modeling, and constrained latent-space steering. Valence and memorability are used only as worked examples. Using more than 36,000 image-fMRI observations from four deeply sampled Natural Scenes Dataset participants, subject-specific models recovered coarse generative structure from visually responsive cortex (two-way identification, 0.79-0.88; chance, 0.5). Graded perturbations were reconstructed as images and evaluated with automated scorers and human ratings from 7,200 trials by 18 participants. In the primary VDVAE model, valence shifted from -0.61 to +1.03 SD and memorability from -1.34 to +1.45 SD; a later Versatile Diffusion refinement reduced or altered these effects. Across five perturbation levels, human valence ratings moved in the predicted direction under the linear time-correction model (mean slope, 0.038 SD per unit of alpha; 95 percent CI, 0.003-0.074; positive in 16 of 18 participants). Perceived memorability did not change reliably. Baseline agreement with the automated assessor was suggestive for valence (r = 0.30) and weak for memorability (r = 0.10). Extreme perturbations drifted from the original stimulus, so intended change must be weighed against loss of fidelity. These findings provide a falsifiable upstream method for designing and behaviorally testing candidate representational targets for future neuromodulation in psychiatry, while marking the limits of the present static approximation.