ABSTRACT NUMBER: ESOC2026A1634 BEYOND CORTICAL LOCALIZATION: FRONTAL CORTICO-SUBCORTICAL CIRCUITS AND CLINICAL SYMPTOMS

Abstract Background and aims The interpretation of neurological symptoms has traditionally relied on cortical localization, assigning each clinical sign to a specific brain area. However, clinical practice and functional neuroimaging have shown limitations of this focal approach. Behavior, language, and movement emerge from dynamic cortico-subcortical networks in which the cortex communicates with the basal ganglia, thalamus, and other deep structures through specific functional loops. Methods We present three patients with distinct clinical manifestations. The first patient, a 71-year-old woman, presented with tremors and bradykinesia. The second patient, a 42-year-old woman, developed headaches, visual impairment, and abulia. The third patient, a 64-year-old woman, presented with fluctuating aphasia and emotional dysregulation. Results In all cases, the diagnostic work-up began with neuroimaging, which revealed frontal lesions involving the subcortical structures. In the first patient, MRI showed compression of the right caudate nucleus and putamen, explaining tremors and bradykinesia through disruption of the dorsolateral frontostriatal motor circuit. In the second patient, a right frontal lesion caused a mass effect on the anterior cingulate cortex and basal ganglia, correlating with abulia due to anterior cingulate circuit dysfunction. In the third patient, compression of the left dorsolateral and orbitofrontal regions was associated with fluctuating aphasia and emotional disinhibition, reflecting dysfunction of the dorsolateral prefrontal and orbitofrontal circuits. Conclusions Dysfunction of cortico-subcortical circuits can produce neurological and behavioral symptoms that mimic cortical or psychiatric syndromes, highlighting the limitations of a purely cortical localization model. A network-based approach improves the clinical interpretation, diagnostic orientation, and prognostic assessment of frontal lesions. Conflict of interest Irene Díaz-Díaz: nothing to disclose Figure 1 - belongs to Results