2026 ECNP Congress

PS01-1145

Mental imagery in anxiety and depressive disorders: neuroimaging correlates for psychotherapy, neurofeedback, and neuromodulation

Giorgio Ratti — C. Bonivento, F. Bottaro, G. Delvecchio, M. Nobile, B. Tomasino, E. Maggioni, P. Brambilla · University of Milan, Department of Pathophysiology and Transplantation, Milan, Italy

2026 ECNP Congress

Introduction

Mental imagery enables sensory-like simulation relevant to autobiographical memory, future anticipation, rehearsal, and threat processing. In anxiety and depressive disorders, maladaptive imagery may involve altered scene generation and heightened emotional reactivity to internally generated images.

Aim(s): We reviewed functional magnetic resonance imaging (fMRI) studies using mental imagery paradigms in anxiety disorders (ANX) and major depressive disorder or clinically relevant depressive symptoms (DEP), focusing on neural systems relevant to psychotherapy, neurofeedback, and neuromodulation.

Methods

PubMed, Scopus, and Web of Science were searched to 30 June 2025 following PRISMA 2020. We included original adult fMRI studies in ANX or DEP samples who completed a mental imagery task. Extracted variables included diagnosis, sample size, task, modality, statistical model and thresholds, and neural and symptom outcomes. Given heterogeneity in diagnoses, paradigms, and outcomes, we used narrative synthesis with descriptive statistics.

Results

The search identified 653 records. Nine studies met inclusion criteria: five in ANX and four in DEP. Across ANX studies, heterogeneity precluded pooling, but findings converged on threat-reactive corticolimbic and prefrontal systems during directed threat imagery and disorder-relevant affective scripts. Buff et al. studied 19 patients with generalised anxiety disorder and 19 controls: disorder-related scripts increased anxiety, arousal, amygdala, dorsomedial and ventrolateral prefrontal, and thalamic activation, with reduced ventromedial prefrontal/subgenual anterior cingulate activity [1]. DEP studies included 61 clinical participants and 53 controls, plus one healthy neurofeedback trainee. Hach et al. used spatiotemporal partial least squares and showed reduced recruitment of hippocampal, parahippocampal, precuneus, and cuneus regions during past and future event construction, alongside weaker hippocampal connectivity [2]. In social imagery, Gillard et al. reported engagement of bilateral insula, thalamus, and pre/postcentral gyrus across groups. Recurrent chronic depression was associated with increased right middle frontal gyrus activation independent of memory type, and positive affect change correlated with dorsal anterior cingulate and insular activity [3]. In first-person state/psychological imagery, Tomasino et al. found differential activation of the left superior frontal gyrus, orbital part, and right putamen in major depressive disorder versus controls [4]. Pereira et al. tested real-time fMRI neurofeedback in seven women with mild to moderate depressive symptoms. Classifier accuracy improved across training (median Session 4 minus Session 1 = 6.563%, range 4.10-27.34, Wilcoxon two-tailed p = 0.031), with improvement on the Hamilton Depression Rating Scale (median = 7, range 2-15, p = 0.016) and Beck Depression Inventory-II (median = 8, range 1-15, p = 0.031). Scores were maintained at 10 days without further significant change [5].

Conclusions

Mental imagery paradigms reveal disorder-relevant neural signatures across ANX and DEP. ANX findings suggest altered corticolimbic responses during threat-related imagery. DEP evidence suggests reduced episodic scene construction within hippocampal-posterior medial systems, together with increased fronto-striatal and salience-related engagement during social or self-referential emotional imagery. These findings provide a neurobiological rationale for imagery-focused psychotherapy and identify candidate targets for neurofeedback and neuromodulation. However, evidence remains limited by small samples, heterogeneous tasks, and few intervention studies. Larger pre-registered multimodal studies are needed before clinical translation can be established.

References

  1. Buff, C., Schmidt, C., Brinkmann, L., Gathmann, B., Tupak, S., Straube, T., 2018. Directed threat imagery in generalized anxiety disorder. Psychol. Med. 48, 617-628. doi:10.1017/S0033291717001957.
  2. Hach, S., Tippett, L.J., Addis, D.R., 2014. Neural changes associated with the generation of specific past and future events in depression. Neuropsychologia 65, 41-55. doi:10.1016/j.neuropsychologia.2014.10.003.
  3. Gillard, J., Werner-Seidler, A., Dalgleish, T., Stretton, J., 2023. Script-driven imagery of socially salient autobiographical memories in major depressive disorder. Sci. Rep. 13, 14577. doi:10.1038/s41598-023-41486-7.
  4. Tomasino, B., Piani, M.C., Maggioni, E., Bonivento, C., D’Agostini, S., Balestrieri, M., Brambilla, P., 2025. First person state/psychological imagery modulates the orbital frontal gyrus and the putamen in individuals with depression. Front. Psychiatry 16, 1583482. doi:10.3389/fpsyt.2025.1583482.
  5. Pereira, J.A., Ray, A., Rana, M., Silva, C., Salinas, C., Zamorano, F., Irani, M., Opazo, P., Sitaram, R., Ruiz, S., 2022. A real-time fMRI neurofeedback system for the clinical alleviation of depression with a subject-independent classification of brain states. Front. Hum. Neurosci. 16, 933559. doi:10.3389/fnhum.2022.933559.