Explicit outcome expectations correlate with specific activation in the caudate nucleus and red nucleusBrain scans show how expectations influence the way we heal

To investigate the characteristics of brain region activation associated with explicit outcome expectation effects in treatment contexts, and to identify core brain regions consistently involved across diverse experimental paradigms. A systematic search was conducted for studies published from January 1, 2014, to December 31, 2025. Functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) studies investigating treatment expectation effects were included. In neuroimaging paradigms, these effects are commonly induced through explicit outcome expectations via verbal instructions or contextual cues. Risk of bias was assessed using the ROB 2.0 and ROBINS-I tools. Activation likelihood estimation (ALE) meta-analysis was performed using GingerALE 3.0.2 based on whole-brain activation coordinates. Results were visualized using Mango software. Sensitivity analyses were performed by excluding the study with the highest risk of bias and using a leave-one-study-out approach. Additionally, a qualitative synthesis of activation foci was conducted across four domains to address paradigm heterogeneity. A total of 21 articles with 855 subjects were included in this study, consisting of 17 randomized controlled trials and 4 non-randomized studies. The risk of bias assessment indicated that only five RCTs were rated as low risk, while approximately three-quarters of studies showed some concerns or high risk. Most studies modulated expectations through interventions such as verbal instruction and pain stimulation. Convergent neuroimaging studies implicated the insula, frontal lobe, striatum, and additional relevant brain regions. The ALE meta-analysis identified two significant activation clusters located in the caudate nucleus/lentiform nucleus and the red nucleus. Sensitivity analyses indicated that the majority of findings remained stable. Qualitative domain-based synthesis further revealed consistent striatal activation across all domains, together with distinct domain-specific activation patterns. The findings of this study suggest that explicit outcome expectation effects, as a core operationalized component of treatment expectation, do not rely on a single brain region but emerge from distributed and dynamically interacting neural systems that depend on reward expectation and information integration. The coordinated activity of multiple brain regions collectively supports the generation of explicit outcome expectations. The striatum serves as a shared core substrate across different expectancy domains, while domain-specific activation reflects functional specialization for distinct contexts. These findings provide important evidence for elucidating the neural correlates of explicit outcome expectation effects and establish a foundation for further brain mechanism-based intervention strategies. Trial Registration: PROSPERO: CRD420251074894.