RT Journal Article SR Electronic T1 GABAergic Dysfunction in Essential Tremor: An 11C-Flumazenil PET Study JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1030 OP 1035 DO 10.2967/jnumed.109.074120 VO 51 IS 7 A1 Henning Boecker A1 Adolf Weindl A1 David J. Brooks A1 Andres O. Ceballos-Baumann A1 Christoph Liedtke A1 Matthias Miederer A1 Till Sprenger A1 Klaus J. Wagner A1 Isabelle Miederer YR 2010 UL http://jnm.snmjournals.org/content/51/7/1030.abstract AB 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.