Objective: To elucidate the role of human cerebellum in the reward processing system, of which a new cerebellar circuitry was recently identified in mice [1].

Background: Recent studies in mouse models have indicated that the cerebellum has a direct connection with the ventral tegmental area [1], a brain region located in midbrain responsible for reward processing and encoding. However, whether the cerebellum modulates the reward circuit in humans still remains unclear. Impulsivity [2] and compulsivity [3] are two symptoms related to abnormal reward processing; therefore, we tested this cerebellar reward hypothesis by studying impulsivity and compulsivity in patients with cerebellar ataxia.

Method: ​​​​We performed a cross-sectional study of 30 cerebellar ataxia patients and 30 age-matched controls recruited from the Ataxia Clinic at Columbia University Medical Center. Impulsivity and compulsivity were measured using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease-Rating Scale (QUIP-RS) [4]. We compared total QUIP-RS and domain-specific subscales of QUIP-RS between ataxic patients and controls. Using linear regression models, we investigated whether the severity of impulsivity and compulsivity was associated with the severity of ataxia, measured by the Scale for Assessment and Rating of Ataxia (SARA) score [5], or depression, measured by Beck’s Depression Inventory (BDI) [6], in ataxia patients.

Results: ​​​​We found that cerebellar ataxia cases have higher total QUIP-RS scores (19.33 ± 15.29 vs. 11.67 ± 8.80, p = 0.006). Individuals with cerebellar ataxia also demonstrated the domain-specific impulsivity and compulsive behaviors in gambling (0.77 ± 1.63 vs. 0.27 ± 0.78, p = 0.007), eating (4.00 ± 3.70 vs. 2.77 ± 2.75, p = 0.035), hobbyism-punding (6.90 ± 6.62 vs. 3.17 ± 3.25, p < 0.001), and excessive medication-use  (2.13 ± 3.28 vs. 0.38 ± 0.85, p < 0.001). Impulsivity and compulsivity, especially impulsive eating (β = 0.845, 95% CI: 0.336 – 1.355, p = 0.001) and excessive medication-use (β = 1.248, 95% CI: 0.647 – 1,849, p < 0.001), are associated with depression (β = 0.168, 95% CI: 0.044 – 0.292, p = 0.008) but not with ataxia (β = 0.062, 95% CI: -0.093 – 0.218, p = 0.419).

Conclusion: ​​​​​​Individuals with cerebellar ataxias are more impulsive and compulsive, and these symptoms might be part of the broader spectrum of the cerebellar cognitive affective syndrome [7].

References: [1] Carta I, Chen CH, Schott AL, et al. Cerebellar modulation of the reward circuitry and social behavior. Science. 2019;363(6424). [2] Burnett Heyes S, Adam RJ, Urner M, et al. Impulsivity and Rapid Decision-Making for Reward. Front Psychol. 2012;3:153. [3] Figee M, Vink M, de Geus F, et al. Dysfunctional reward circuitry in obsessive-compulsive disorder. Biol Psychiatry. 2011;69(9):867-74 [4] Weintraub D, Hoops S, Shea JA, et al. Validation of the questionnaire for impulsive-compulsive disorders in Parkinson’s disease. Mov Disord. 2009;24(10):1461-7. [5] Schmitz-Hübsch T, du Montcel ST, Baliko L, et al. Scale for the assessment and rating of ataxia: development of a new clinical scale. Neurology. 2006;66(11):1717-20. [6] Beck, A.T., Ward, C. H., Mendelson, M, et al. An inventory for measuring depression. Arch Gen Psychiatry. 1961;4:561-71. [7] Argyropoulos GPD, van Dun K, Adamaszek M, et al. The Cerebellar Cognitive Affective/Schmahmann Syndrome: a Task Force Paper. Cerebellum. 2020;19(1):102-125.

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