TY - JOUR T1 - GABAergic Dysfunction in Essential Tremor: An <sup>11</sup>C-Flumazenil PET Study JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1030 LP - 1035 DO - 10.2967/jnumed.109.074120 VL - 51 IS - 7 AU - Henning Boecker AU - Adolf Weindl AU - David J. Brooks AU - Andres O. Ceballos-Baumann AU - Christoph Liedtke AU - Matthias Miederer AU - Till Sprenger AU - Klaus J. Wagner AU - Isabelle Miederer Y1 - 2010/07/01 UR - http://jnm.snmjournals.org/content/51/7/1030.abstract N2 - Essential tremor is the most common movement disorder, but the underlying pathophysiology is not well understood. A primary overactivity of cerebellothalamic output pathways is the most conspicuous finding, as indicated by animal and human studies. It has been argued that this overactivity may be due to impaired central inhibition, and converging evidence points toward a potential role of γ-aminobutyric acid (GABA) dysfunction in tremor generation. Methods: Using 11C-flumazenil and PET, we calculated the distribution volume, an index of availability of benzodiazepine receptor sites of the GABAA complex, in a group of 8 patients with bilateral essential tremor, as compared with 11 healthy controls. Results: Significant increases in binding of 11C-flumazenil at the benzodiazepine receptor site of the GABAA receptor in the cerebellum, the ventrolateral thalamus, and the lateral premotor cortex were identified in the essential tremor group. Conclusion: Essential tremor is associated with reduced GABAergic function and increased availability of benzodiazepine receptor sites in brain regions implicated specifically in tremor genesis. This finding is thought to reflect overactivity of cerebellothalamic circuits and, hence, lends support to the “GABA hypothesis” of essential tremor. ER -