Abstract: A striking neurochemical form of compartmentalization has been found in the striatum of humans and other species, dividing it into striosomes and matrix. The function of this organization has been unclear, but the anatomical connections of striosomes indicate their relation to emotion-related brain regions including the medial prefrontal cortex. Here, I will present the first evidence of the cortical-striosomal circuit function in approach-avoidance conflict conditions known to evoke anxiety in humans. My work elucidates that chronic stress leads to dysfunction of the cortical-striosomal circuit, causing abnormal decision-making. Additionally, I will present novel methods for neuronal circuit isolation and decoding that significantly extend the scope of analysis of the multi-dimensional non-linear networks present in the striatum and other brain regions. My findings demonstrate that cognitive and emotion-related functions, like sensory-motor processing, are subject to encoding within compartmentally organized representations in the forebrain. Decoding of the cortical-striosomal circuit may lead to development of treatment for stress-related disorders.