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

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.

Empagliflozin attenuates neurodegeneration through antioxidant, anti-inflammatory, and modulation of α-synuclein and Parkin levels in rotenone-induced Parkinson’s disease in rats

“…The neurodegeneration process appears as a consequence of dopaminergic neurons damage in substantia nigra, inducing a marked decline in the striatum levels of dopamine (DP) ( Acar et al, 2019 ). Although most research has focused on the basal ganglia in Parkinson's disease pathology, some evidence suggests that the cerebellum also contributes to PD related to motor and cognitive decline through the loss of Purkinje cells neurons, which were present in the cerebellum and were responsible for regulating and coordinating movement via releasing of GABA neurotransmitter ( Hasan et al, 2020a , Piras et al, 2021 ). Globally, PD affects 1% of people over the age of 60 and 5% of people over the age of 85 ( Balestrassi and Silva, 2021 ).…”

Reduced Hippocampal GABA+ Is Associated With Poorer Episodic Memory in Healthy Older Women: A Pilot Study

“…Likewise, several studies reported that GABA+ concentrations in the dorsal anterior cingulate and in the occipital cortex are associated with measures of executive and visuo-perceptual functions, respectively (Marenco et al, 2018;Simmonite et al, 2019). Furthermore, Piras et al (2019Piras et al ( , 2020 found cerebral GABA levels to be associated with performance in phonemic fluency and in the Stroop Color-Word Test, a measure of response inhibition (Piras et al, 2019(Piras et al, , 2020). Thus, it is possible that the relation between GABA+ levels and cognition is not specific to memory.…”

The Relative Contribution of Cochlear Synaptopathy and Reduced Inhibition to Age-Related Hearing Impairment for People With Normal Audiograms

“…Therefore, the wave V/I amplitude ratio may not be a good indicator for central GABAergic inhibition, which may explain the lack of a correlation between this measure and the SCWT inhibition score. Thus, it remains possible that the SCWT inhibition score provides a measure of central GABAergic inhibition as indicated by the magnetic resonance spectroscopy studies on the relation between GABA levels and SCWT performance (e.g., Kühn et al, 2016; Mamiya et al, 2021; Piras et al, 2021; Sofuoglu et al, 2005).…”

“…We found an association between decreased inhibition, as assessed by the SCWT, and worse auditory temporal processing and SRTN (Figure 5A-C). Although the SCWT measures behavioral inhibition, GABA magnetic resonance spectroscopy studies have shown that performance of the SCWT is accompanied by GABA increases in the anterior cingulate cortex (Kühn et al, 2016), the caudate nucleus in the front-striatal circuitry (Mamiya et al, 2021) and the cerebellum (Piras et al, 2021). Furthermore, Sofuoglu et al (2005) showed that increasing synaptic GABA levels enhanced Stroop interference inhibition in a clinical study.…”

“…The Stroop test is widely and primarily used to assess the ability to inhibit cognitive interference that occurs when the processing of a specific stimulus feature impedes the simultaneous processing of a second stimulus feature, for example, when naming the ink color in which a color name is printed. Stroop inhibition, however, has also been associated with GABA levels in the brain (e.g., Kühn et al, 2016; Mamiya et al, 2021; Piras et al, 2021; Sofuoglu et al, 2005). Here, the Stroop test was used to directly assess the ability to inhibit cognitive interference as well as to indirectly assess GABA levels (Figure 1).…”