Loss of inhibition in sensorimotor networks in focal hand dystonia.

Abstract

OBJECTIVE:

To investigate GABA-ergic receptor density and associated brain functional and grey matter changes in focal hand dystonia (FHD).

METHODS:

18 patients with FHD of the right hand and 18 age and gender matched healthy volunteers (HV) participated in this study. We measured the density of GABA-A receptors using [11C] Flumazenil and perfusion using [15O] H2O. Anatomical images were also used to measure grey matter volume with voxel-based morphometry (VBM).

RESULTS:

In FHD patients compared to HV, the vermis VI of the right cerebellum and the left sensorimotor cortex had a decrease of Flumazenil binding potential (FMZ-BP), whereas the striatum and the lateral cerebellum did not show significant change. Bilateral inferior prefrontal cortex had increased FMZ-BP and an increase of perfusion, which correlated negatively with disease duration. Only the left sensorimotor cortex showed a decrease of grey matter volume.

INTERPRETATION:

Impairments of GABAergic neurotransmission in the cerebellum and the sensorimotor cortical areas could explain different aspects of loss of inhibitory control in FHD, the former being involved in maladaptive plasticity, the latter in surround inhibition. Reorganization of the inferior prefrontal cortices, part of the associative network, might be compensatory for the loss of inhibitory control in sensorimotor circuits. These findings suggest that cerebellar and cerebral GABAergic abnormalities could play a role in the functional imbalance of striato-cerebello-cortical loops in dystonia.

• Authors: Cecile Gallea, Priyantha Herath, Valerie Voon, Alicja Lerner, John Ostuni, Ziad Saad, Shantalaxmi Thada, Jeffrey Solomon, Silvina G Horovitz, Mark Hallett
• Journal: NeuroImage. Clinical (Neuroimage Clin) Vol. 17 Pg. 90-97 ( 2018) ISSN: 2213-1582 [Electronic] Netherlands
• PMID: 29062685 (Publication Type: Journal Article)

Chemical References

• Carbon Radioisotopes
• GABA Modulators
• Oxygen Isotopes
• Oxygen Radioisotopes
• Flumazenil

Topics

• Adult
• Aged
• Brain Mapping
• Carbon Radioisotopes (pharmacokinetics)
• Case-Control Studies
• Cerebellum (diagnostic imaging, drug effects)
• Cerebrovascular Circulation
• Dystonic Disorders (diagnostic imaging, pathology)
• Female
• Flumazenil (pharmacokinetics)
• GABA Modulators (pharmacokinetics)
• Humans
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Neural Pathways (diagnostic imaging)
• Oxygen Isotopes (pharmacokinetics)
• Oxygen Radioisotopes (pharmacokinetics)
• Positron-Emission Tomography
• Prefrontal Cortex (diagnostic imaging, drug effects)
• Young Adult