Cognitive abilities are impaired in neurodevelopmental disorders, including 
autism spectrum disorder (ASD) and schizophrenia. Preclinical models with strong 
endophenotypes relevant to cognitive dysfunctions offer a valuable resource for 
therapeutic development. However, improved assays to test higher order cognition 
are needed. We employed touchscreen technology to design a complex transitive 
inference (TI) assay that requires cognitive flexibility and relational 
learning. C57BL/6J (B6) mice with good cognitive skills and BTBR T+tf/J (BTBR), 
a model of ASD with cognitive deficits, were evaluated in simple and complex 
touchscreen assays. Both B6 and BTBR acquired visual discrimination and 
reversal. BTBR displayed deficits on components of TI, when 4 stimuli pairs were 
interspersed, which required flexible integrated knowledge. BTBR displayed 
impairment on the A > E inference, analogous to the A > E deficit in ASD. B6 and 
BTBR mice both reached criterion on the B > D comparison, unlike the B > D 
impairment in schizophrenia. These results demonstrate that mice are capable of 
complex discriminations and higher order tasks using methods and equipment 
paralleling those used in humans. Our discovery that a mouse model of ASD 
displays a TI deficit similar to humans with ASD supports the use of the 
touchscreen technology for complex cognitive tasks in mouse models of 
neurodevelopmental disorders.