GABAergic changes in the thalamocortical circuit in Parkinson's disease.

Parkinson's disease is characterized by bradykinesia, rigidity, and tremor. These symptoms have been related to an increased gamma-aminobutyric acid (GABA)ergic inhibitory drive from globus pallidus onto the thalamus. However, in vivo empirical evidence for the role of GABA in Parkinson's disease is limited. Some discrepancies in the literature may be explained by the presence or absence of tremor. Specifically, recent functional magnetic resonance imaging (fMRI) findings suggest that Parkinson's tremor is associated with reduced, dopamine-dependent thalamic inhibition. Here, we tested the hypothesis that GABA in the thalamocortical motor circuit is increased in Parkinson's disease, and we explored differences between clinical phenotypes. We included 60 Parkinson patients with dopamine-resistant tremor (n = 17), dopamine-responsive tremor (n = 23), or no tremor (n = 20), and healthy controls (n = 22). Using magnetic resonance spectroscopy, we measured GABA-to-total-creatine ratio in motor cortex, thalamus, and a control region (visual cortex) on two separate days (ON and OFF dopaminergic medication). GABA levels were unaltered by Parkinson's disease, clinical phenotype, or medication. However, motor cortex GABA levels were inversely correlated with disease severity, particularly rigidity and tremor, both ON and OFF medication. We conclude that cortical GABA plays a beneficial rather than a detrimental role in Parkinson's disease, and that GABA depletion may contribute to increased motor symptom expression.

Magnetic Resonance Imaging-guided Focused Ultrasound Thalamotomy for Parkinson's Disease.

Thalamotomy is effective in treating refractory tremor in Parkinson's disease (PD). We herein report a PD patient who underwent left ventral intermediate nucleus and ventro oralis posterior nucleus thalamotomy using magnetic resonance imaging-guided focused ultrasound (MRgFUS). Right-side resting tremor and rigidity were abolished immediately following the ultrasound energy delivery. In addition, left-side resting tremor and rigidity also improved. No adverse events occurred during the procedure. We observed the exacerbation of bradykinesia, which might have been caused by edema around the target. This is the first report of thalamotomy using MRgFUS for PD patient from Japan. Further investigations concerning the efficacy and safety of this procedure are necessary.