Behavioral Proxy Validity in Macaque Neuroscience: Developmental Competence and Contextual Interpretability

Behavioral measures are central to nonhuman primate neuroscience, but their use as proxies for cognitive, affective, or clinical constructs requires more than accurate detection. We argue that behavioral inference depends primarily on two often- underexamined prerequisites: developmental competence and contextual interpretability. Developmental competence requires that the animal has acquired the experience, repertoire, and physiological capacity to express the target behavior. Contextual interpretability requires that functional significance be evaluated within the animal's developmental, social, and experimental setting. Without these prerequisites, immaturity or restricted rearing may mimic dysfunction, and adaptive coping may be mislabeled as pathology. We illustrate how proxies fail through developmental immaturity, definitional ambiguity, multifunctionality, and circular validation, and synthesize these considerations into a three-stage operational framework-Define, Interpret, and Validate-for evaluating behavioral proxies. To assess how frequently these inferential gaps occur in current practice, we conducted a mini-review of depression-related behavioral proxies across 56 macaque studies. We found that rearing history was sufficiently reported in only 17.9% of studies; operational definitions were increasingly omitted (from 26.3% absent in 2010-2019 to 58.3% in 2020-2026); contextual interpretation was considered in only 26.8%; and independent validation preceded model assignment in only 3.6%. These findings highlight the need for better-supported proxies, requiring developmental conditions aligned with experimental aims, a reproducible inferential workflow, and integration of ethological expertise with neural and physiological validation. Behavioral proxies should be treated not as convenient readouts but as construct-linked hypotheses to be defined, interpreted, and validated.