Changes in GABA and glutamate concentrations during memory tasks in patients with Parkinson’s disease undergoing DBS surgery

Abstract

Until now direct neurochemical measurements during memory tasks have not been accomplished in the human basal ganglia. It has been proposed, based on both functional imaging studies and psychometric testing in normal subjects and in patients with Parkinson’s disease (PD), that the basal ganglia is responsible for the performance of feedback-contingent implicit memory tasks. To measure neurotransmitters, we used in vivo microdialysis during deep brain stimulation (DBS) surgery. We show in the right subthalamic nucleus (STN) of patients with PD a task-dependent change in the concentrations of glutamate and GABA during an implicit memory task relative to baseline, while no difference was found between declarative memory tasks. The five patients studied had a significant decrease in the percent concentration of GABA and glutamate during the performance of the weather prediction task (WPT). We hypothesize, based on current models of basal ganglia function, that this decrease in the concentration is consistent with expected dysfunction in basal ganglia networks in patients with PD.

Deep Brain Stimulation Modified Autism-Like Deficits via the Serotonin System in a Valproic Acid-Induced Rat Model

“…A previous study demonstrated that high-frequency DBS induced dyskinesia by activating NMDAR subunit NR2B, while another study revealed that DBS with stimulation in the frequency range of 100–200 Hz maximally activated extrasynaptic NMDARs subunit NR2B [ 72 , 73 ]. Previous studies revealed that DBS not only reduced the concentration of glutamate, but also the expression of GABA, during cognitive testing [ 74 , 75 ]. High-frequency stimulation suppresses spontaneous neuronal firing, suggesting that the stimulus intensity may regulate the inhibitory interneurons [ 76 ].…”

Inhibitory motor dysfunction in parkinson's disease subtypes

“…Similarly, either elevated BG GABA levels (24,25) or reduced left striatum GABA levels (26) have been reported in animal studies. Our study showed reduced GABA+ levels in a BG region, which includes the striatum.…”

“…In previous human studies, GABA levels in the striatum or putamen have been reported to be either reduced, 22 unaltered, 14 or elevated 13,23 in PD compared with healthy controls. Similarly, either elevated BG GABA levels 24,25 or reduced left striatum GABA levels 26 have been reported in animal studies. Our study showed reduced GABA 1 levels in a BG region, which includes the striatum.…”

Deep Brain Stimulation to Alleviate Freezing of Gait and Cognitive Dysfunction in Parkinson's Disease: Update on Current Research and Future Perspectives

“…It was demonstrated in hemiparkinsonian rats that 6-hydroxydopamine lesioning increased the levels of glutamate and gamma-amino butyric acid (GABA) in striatum and SNr, which could be normalized by chronic STN-DBS (Chassain et al, 2016 ). As glutamate and GABA are closely related to the memory function in PD patients (Buchanan et al, 2014 ), it suggests STN-DBS may influence the basal ganglia networks which are associated with cognitive functions. Meanwhile, since pedunculopontine tegmental nucleus (PPTg) acts as an interface between the basal ganglia and cerebellum, it has potentials to influence motor control as well as cognitive functions (Mori et al, 2016 ).…”