Striatal and thalamic GABA level concentrations play differential roles for the modulation of response selection processes by proprioceptive information

Abstract

The selection of appropriate responses is a complex endeavor requiring the integration of many different sources of information in fronto-striatal-thalamic circuits. An often neglected but relevant piece of information is provided by proprioceptive inputs about the current position of our limbs. This study examines the importance of striatal and thalamic GABA levels in these processes using GABA-edited magnetic resonance spectroscopy (GABAMRS) and a Simon task featuring proprioception-induced interference in healthy subjects. As a possible model of deficits in the processing of proprioceptive information, we also included Parkinson's disease (PD) patients in this study. The results show that proprioceptive information about unusual postures complicates response selection processes in controls, but not in PD patients. The well-known deficits of PD patients in processing proprioceptive information can turn into a benefit when altered proprioceptive information would normally complicate response selection processes. Striatal and thalamic GABA levels play dissociable roles in the modulation of response selection processes by proprioceptive information: Striatal GABA levels seem to be important for the general speed of responding, most likely because striatal GABA promotes response selection. In contrast, the modulation of response conflict by proprioceptive information is closely related to thalamic GABA concentrations with higher concentration being related to a smaller response conflict effect. The most likely explanation for this finding is that the thalamus is involved in the integration of sensorimotor, attentional, and cognitive information for the purpose of response formation. Yet, this effect in the thalamus vanishes when controls and PD patients were analyzed separately.

Individual Differences in Resting Corticospinal Excitability Are Correlated with Reaction Time and GABA Content in Motor Cortex

“…Similar to what we observed here between GABA and CS excitability, these other processes may also be sensitive to GABA availability. Interestingly, our findings were regionally specific to M1, similar to other reports relating GABA concentrations to physiological or behavioral measures (Grachev and Apkarian, 2000;Grachev et al, 2001;Boy et al, 2011;Dharmadhikari et al, 2015;Durst et al, 2015;Heba et al, 2016;Mikkelsen et al, 2016). GABA concentration in the three other cortical regions measured showed no relationship with CS excitability.…”

Individual differences in GABA content are reliable but are not uniform across the human cortex

“…Abnormalities in GABA concentrations have been associated with neurological diseases and trauma (Blicher et al, 2015; Dharmadhikari et al, 2015; Draper et al, 2014; Hattingen et al, 2014; van der Hel et al, 2013). Given the reliability observed here in healthy individuals, it may be possible to relate local changes in GABA to patterns of recovery.…”

Inhibitory motor dysfunction in parkinson's disease subtypes

“…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.…”

“…Firstly, a larger VOI (included striatum, globus pallidus, part of thalamus, and other gray- and white-matter structures) was chosen for our study (3 × 3 × 2 cm 3 ) because of the different data acquisition strategy. Indeed, thalamic GABA levels in references (22) and (14) are significantly reduced. Secondly, there are differences between methodologies – our study is closest in methodology to (14).…”

“…Indeed, thalamic GABA levels in references (22) and (14) are significantly reduced. Secondly, there are differences between methodologies – our study is closest in methodology to (14). And in this study, water was used as reference to quantify GABA levels rather than Cr (24,27).…”