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. 2020 Dec 28;11(1):16.
doi: 10.3390/jpm11010016.

Cerebellar GABA Levels and Cognitive Interference in Parkinson's disease and Healthy Comparators

Federica Piras  1 , Daniela Vecchio  1 , Francesca Assogna  1 , Clelia Pellicano  1 , Valentina Ciullo  1 , Nerisa Banaj  1 , Richard A E Edden  2 , Francesco E Pontieri  3 , Fabrizio Piras  1 , Gianfranco Spalletta  1   4
Affiliations

Cerebellar GABA Levels and Cognitive Interference in Parkinson's disease and Healthy Comparators

Federica Piras et al. J Pers Med. .

Abstract

The neuroanatomical and molecular substrates for cognitive impairment in Parkinson Disease (PD) are far from clear. Evidence suggests a non-dopaminergic basis, and a crucial role for cerebellum in cognitive control in PD. We investigated whether a PD cognitive marker (response inhibition) was differently controlled by g-amino butyric acid (GABA) and/or by glutamate-glutamine (Glx) levels in the cerebellum of idiopathic PD patients, and healthy comparators (HC). Magnetic resonance spectroscopy of GABA/Glx (MEGA-PRESS acquisition sequence) was performed at 3 Tesla, and response inhibition assessed by the Stroop Word-Color Test (SWCT) and the Wisconsin Card Sorting Test (WCST). Linear correlations between cerebellar GABA/Glx levels, SWCT time/error interference effects and WCST perseverative errors were performed to test differences between correlation coefficients in PD and HC. Results showed that higher levels of mean cerebellar GABA were associated to SWCT increased time and error interference effects in PD, and the contrary in HC. Such effect dissociated by hemisphere, while correlation coefficients differences were significant in both right and left cerebellum. We conclude that MRS measured levels of cerebellar GABA are related in PD patients with decreased efficiency in filtering task-irrelevant information. This is crucial for developing pharmacological treatments for PD to potentially preserve cognitive functioning.

Keywords: GABAergic signaling; MRS; Parkinson’s Disease; cerebellum; cognition; response inhibition.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Cerebellar GABA and Glx spectra. Legend: (A) Voxel placement in the right hemisphere; (B) acquired Magnetic Resonance Spectroscopy (MRS) spectra with gamma-aminobutyric acid (GABA) and Glutamate/Glutamine complex (Glx) peaks in red, and (C) zoom on GABA and Glx peaks: acquired data are in blue, fit in red and residual in black.
Figure 2
Figure 2
Bivariate scattergrams of the differential relationship in experimental groups between cerebellar gamma-aminobutyric acid (GABA) and cognitive interference. Legend: (A) right and (B) left and right mean values of GABA cerebellar concentration and response inhibition performance in patients diagnosed with Parkinson Disease (PD) and Healthy Comparators (HC), as measured through the time (in seconds) Interference Effect of the Stroop Word-Color Test short version (SWCT sv IE-Time). ppm: parts per million.
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