Internal segment of globus pallidum leads cortex during error detection: evidence from invasive electrophysiological recordings in dystonia patients

Introduction:Learning new motor tasks requires the ability to monitor ongoing behavior, detect errors and modify the performance accordingly. The generators of the corresponding ERP (error-related negativity, ERN) have been localized in the posterior frontomedian cortex (pFMC) that is intimately connected with the basal ganglia. However, the specific role of the basal ganglia in error-detection, as well as the interaction of the BG with the cortical regions during error-processing remains unclear. Here, we aim to investigate the modulation of neuronal activity in the internal segment of the globus pallidum (GPi) – as main output structure of the BG – by error-detection and conflict-processing.

Method: We recorded local field potentials (LFPs) from the GPi and simultaneous surface EEG (FCz, Cz and Pz) in 10 patients undergoing deep brain stimulation for therapy resistant cervical or segmental dystonia during performance of a flanker paradigm, which elicits laterality mistakes in motor responses. LFPs were recorded bipolarly from adjacent contact pairs of the DBS electrode.

Behavioral data were analysed according to task conditions (congruent/incongruent and correct/incorrect trials). Standard ERP analysis was performed in LFP and EEG signals by averaging response-locked epochs during incongruent correct and incongruent erroneous responses. The result was normalized to the pre-stimulus baseline level (from 100 to 300ms pre-stimulus). Statistical analyses were performed by means of nonparametric pair-wise permutation tests with the difference in sample means as test statistic.

Results: Reaction times in incongruent trials were larger for errors than for correct responses (trend, p=0.07). In GPi-LFPs, the ERP between –100 and 100ms around the button press showed a significantly larger amplitude in error compared to correct incongruent trials (p=0.001) with a maximal difference amplitude at 40ms. In the scalp ERP, the ERN was observed in the difference waveforms of error and correct incongruent trials between 70 and 140ms (p=0.012) and reached its maximum at 120ms.

Conclusions: Our finding of a pallidal error-related ERP suggests that the GPi encodes error processing or is involved in the transmission of information related to erroneous motor responses. Furthermore, the pallidal ERN peaked 80ms earlier than the cortical ERN, which may hint at basal ganglia activity being a precursor and modulator of cortical error-signals.