PT - JOURNAL ARTICLE AU - Batsikadze, Giorgi AU - Pakusch, Johanna AU - Klein, Michael AU - Ernst, Thomas Michael AU - Thieme, Andreas AU - Nicksirat, Seyed Ali AU - Steiner, Katharina Marie AU - Nio, Enzo AU - Genc, Erhan AU - Maderwald, Stefan AU - Deuschl, Cornelius AU - Merz, Christian Josef AU - Quick, Harald H. AU - Mark, Melanie D. AU - Timmann, Dagmar TI - Mild Deficits in Fear Learning: Evidence from Humans and Mice with Cerebellar Cortical Degeneration AID - 10.1523/ENEURO.0365-23.2023 DP - 2024 Feb 01 TA - eneuro PG - ENEURO.0365-23.2023 VI - 11 IP - 2 4099 - http://www.eneuro.org/content/11/2/ENEURO.0365-23.2023.short 4100 - http://www.eneuro.org/content/11/2/ENEURO.0365-23.2023.full SO - eNeuro2024 Feb 01; 11 AB - Functional brain imaging studies in humans suggest involvement of the cerebellum in fear conditioning but do not allow conclusions about the functional significance. The main aim of the present study was to examine whether patients with cerebellar degeneration show impaired fear conditioning and whether this is accompanied by alterations in cerebellar cortical activations. To this end, a 2 d differential fear conditioning study was conducted in 20 cerebellar patients and 21 control subjects using a 7 tesla (7 T) MRI system. Fear acquisition and extinction training were performed on day 1, followed by recall on day 2. Cerebellar patients learned to differentiate between the CS+ and CS−. Acquisition and consolidation of learned fear, however, was slowed. Additionally, extinction learning appeared to be delayed. The fMRI signal was reduced in relation to the prediction of the aversive stimulus and altered in relation to its unexpected omission. Similarly, mice with cerebellar cortical degeneration (spinocerebellar ataxia type 6, SCA6) were able to learn the fear association, but retrieval of fear memory was reduced. In sum, cerebellar cortical degeneration led to mild abnormalities in the acquisition of learned fear responses in both humans and mice, particularly manifesting postacquisition training. Future research is warranted to investigate the basis of altered fMRI signals related to fear learning.