Cerebellar Functional Abnormalities in Schizophrenia Are Suggested by Classical Eyeblink Conditioning

nia may result from disruptions in a cortico–cerebellar– thalamic–cortical circuit (CCTCC) producing a mental incoordination or “cognitive dysmetria. ” To further eval-uate the cerebellar contribution to this disrupted circuitry, medication-free patients with schizophrenia completed classical eyeblink conditioning, a cerebellar-mediated learning task. Methods: For classical eyeblink conditioning, 70 trials with a tone conditioned stimulus (CS) and air puff uncon-ditioned stimulus (US) were presented to 15 patients with schizophrenia and 15 healthy control subjects. Acquisition rate for the conditioned response (CR) and response timing were compared between the two groups. Results: Patients with schizophrenia displayed facilitated conditioning compared to control subjects based on a greater number of CRs during the session and a faster acquisition of the learned response. Conclusions: Facilitated conditioning suggests that an enhanced excitability in the cerebellum occurs as part of a disrupted CCTCC in schizophrenia. The enhanced cere-bellar-mediated associative learning may be maladaptive in the context of normal cerebro–cerebellar interactions, leading to the characteristic motor and mental incoordi-nation of the disorder. Classical eyeblink conditioning may provide a useful model system for studying cerebellar involvement in the pathogenesis and treatment of schizo-phrenia. Biol Psychiatry 2000;48:204–209 © 2000 So-ciety of Biological Psychiatr