Annika Sauter: Forschungsaufenthalt an der University of Oxford
Background
As part of my PhD project, I investigate the role of the subthalamic nucleus (STN) in motor and cognitive aspects of response control in people with Parkinson’s disease (PD). The STN serves as an integrative control hub within cortico-subcortical control networks, regulating behavior according to internal goals and external demands.
Its role in tuning behavioral output, refining decision thresholds, timing or flexibility is increasingly acknowledged.
Key to this research is the use of deep brain stimulation (DBS), a therapeutic intervention that improves PD motor symptoms through STN stimulation and provides unique insights into its causal contribution to these functions.
It is evident that motor and cognitive control mechanisms are tightly linked. Yet, how the STN contributes to this converging control function remains underexplored.
In a study involving 24 people with PD receiving STN DBS, we employed a novel cueing/conflict paradigm that combines motor control and cognitive control mechanisms. Simultaneously, we recorded cortical electroencephalography (EEG) signals and local field potentials (LFPs) from the STN to explore their putatively shared oscillatory characteristics. Owing to recent technological advances, sensing-enabled DBS implanted pulse generators (IPGs) enable chronic LFP recordings, i.e., outside perisurgical settings, both during active and inactive DBS.
Given the novelty of this recording technique and various pitfalls when analyzing artifact-prone LFP signals, I seeked the expertise of the Tan group with Prof. Dr. Huiling Tan at the University of Oxford, one of the most renowned research groups in this field. The goal of my research stay was to refine my understanding of LFP signal characteristics and to acquire new methodological approaches for corticosubcortical analyses of oscillatory dynamics with regard to our research questions. This stay was generously supported by the Graduate School of the Faculty of Human Sciences.
Research Stay Objectives
A) Customized EEG/LFP Preprocessing Pipeline
A major challenge in combined EEG/LFP recordings is the offline synchronization of signals via time stamps of stimulation artifacts, due to the absence of event markers in LFP data and different sampling rates (EEG: 1000 Hz; LFP: 250 Hz). Additional pitfalls include potential stimulation-induced artifacts and signal distortions (e.g. sub-harmonics) as well as intrinsic LFP recording noise. The Spike2 software (Cambridge Electronic Design; RRID: SCR_000903), routinely used in the Tan group, can facilitate these issues substantially. A key aim of the research stay was thus to gain proficiency in Spike2. Guided by the group’s expertise, this would be a stepping stone to develop a tailored preprocessing pipeline.
B) Fine-tuned analyses to investigate oscillatory dynamics of response reprogramming and conflict resolution
Core to our research was to detect potentially shared oscillatory dynamics underlying response reprogramming and conflict resolution at cortical and STN level, which required time-frequency (TF) transformation of preprocessed data to obtain power values. Therefore, another key goal of the stay was to establish a robust approach for analyzing ON and OFF DBS recordings, including selecting suitable normalization techniques and TF parameters to allow for valid comparisons between conditions. In-depth discussions and the group members’ expertise would be integral to this step.
C) International networking, interdisciplinary exchange and method transfer
In addition to project-related expertise, another key goal of the stay was to broaden my research and personal perspective through interdisciplinary exchange in an international setting. The Tan group is embedded in the Oxford Brain Networks Dynamics Unit, which offers regular seminars and network opportunities, potentially fostering future collaborations. Furthermore, the acquired expertise would also benefit future EEG/LFP projects in my home working group at the University Clinic Cologne, to which I could contribute after my return.
Results
A) Customized EEG/LFP Preprocessing Pipeline
I successfully completed the synchronization of EEG and LFP channels by identifying systematic features of the synchronization artifacts using Spike2. Furthermore, time alignment could be validated via cross-correlations of event-related potentials (ERPs). Discussions with the Tan group and hands-on use of the software deepened my understanding of key LFP signal characteristics, such as ECG artifacts and movement-related spikes, and how they are modulated by filtering and other processing steps.
Based on these insights, I established a customized preprocessing pipeline optimized to preserve relevant effects while minimizing stimulation-related noise, which enables valid ON/OFF comparisons.
B) Fine-tuned analyses to investigate oscillatory dynamics of response reprogramming and conflict
resolution networks
Preprocessed EEG and LFP data were time-frequency (TF) transformed using adapted Hilbert transform functions established by the Tan group. In order to isolate task-related power dynamics across ON and OFF stimulation states, a custom normalization was applied by subtracting the mean frequency power of each epoch. Power differences at cortical and STN levels were analyzed using linear mixed-effects models (LMEs) and interpreted in discussion with the group.
The results revealed shared oscillatory signatures in the lower beta sub-band (LBB; 13–20 Hz) during both response reprogramming (motor control) and conflict resolution (cognitive control) within a fronto-subthalamic network. LBB is principal to PD pathology, as PD motor symptoms are alleviated by LBB suppression through DBS, revealing the central contribution to motor control. Beta synchronization (BBS) has been associated with reduced behavioral flexibility even beyond outright motor control, by stabilizing motor or cognitive states. As a complementary mechanism, beta desynchronization (BBD), appears to promote behavioral flexibility and adaptations across domains.
Our results align with this framework: enhanced pre-response low beta desynchronization (LBBD) was evident in both response reprogramming and conflict resolution, however, differing in cortical topography and sensitivity to DBS. Conflict resolution involved fronto-central LBBD, whereas response reprogramming elicited slightly right-lateralized frontal LBBD, supporting previous studies linking right prefrontal regions to motor planning and control. At the STN, LBBD was only significantly enhanced for conflict resolution. It is, however, conceivable that the limited sample size precluded a STN LBBD signature for reprogramming. In fact, we found a significant impact of STN LBB on error probability, enhancing error rates with increasing LBB (less flexibility) for trials requiring simultaneous reprogramming and conflict resolution. Moreover, DBS selectively influenced reprogramming, for which LBBD was only observed during the OFF state. This suggests that DBS may interfere with anticipatory inhibition of alternative responses, which is beneficial in case the cue was invalid and the alternative response is demanded (diminished reprogramming costs thus absent LBBD). Together, these results add to a growing understanding of how shared LBB dynamics underpin control across motor and cognitive domains. Importantly, differences in DBS modulation and cortical localization suggest partially distinct deployment depending on the type of adjustment.
C) International networking, interdisciplinary exchange and method transfer
During my stay, I had the opportunity to engage with researchers across disciplines at the University of Oxford and refined my analyses with valuable input from the Tan group, who supported me even beyond the period of the stay. This experience broadened my perspective and enhanced our own group’s methodological repertoire, including the implementation of Spike2 in future LFP projects.