Localization of the subthalamic nucleus in Parkinson disease using multiunit activity

Abstract

Background: Refinement of the subthalamic nucleus (STN) coordinates using intraoperative microelectrode recordings (MER) is routinely performed during deep brain stimulation (DBS) surgeries in Parkinson disease (PD). The commonly used criteria for electrophysiological localization of the STN are qualitative. The goal of this study was to validate quantitative STN detection algorithm (QD) derived from the multi-unit activity in a prospective setting.

Methods: Ten PD patients underwent STN DBS surgery. The MUA was obtained by removing large spikes close to microelectrode using wavelet method and integrating the 500-2000Hz band in the power spectral density. The qualitative intraoperative mapping of the STN using MER (IOM) versus QD was compared using Bland-Altman and Pearson's correlation analysis.

Results: The clinical efficacy was confirmed in all subjects. The mean difference between IOM and QD of the dorsal/ventral border was 0.31±0.84/0.44±0.47mm. Using Bland-Altman statistic, only 2/36 (5.6%) differences (one for the dorsal border and one for the ventral border) were out of ±2 sd line of measurement differences. Correlation between dorsal border/ventral border positions obtained by IOM and QD was 0.79, p<0.0001/0.91, p<0.0001.

Conclusion: Both methods are in reasonable agreement and are strongly correlated. The QD gives objective coordinates of the STN borders at high precision and may be more accurate than IOM. Prospective blinded comparative studies where the DBS leads will be placed using either QD or IOM are warranted.

Figure 1

An example of the post-operative imaging with implanted DBS leads. Axial (A) and coronal (B) images showed the DBS leads inside the STN at both sides. Data from subject #5.

Figure 2

Example of a raw MER and data despiking. Upper panel shows one second of the STN activity superimposed upon the despiked neuronal activity. Lower panel (duration of the signal is 0.007 sec) shows a single spike that was detected and removed from the neuronal signal.

Figure 3

A typical profile of MUA during DBS surgery. The advancing microelectrode moves from left to right towards the anatomical target that is at 0 mm on the x axis. The microelectrode crosses the thalamus, the zona incerta (ZI), STN and the substantia nigra (SN). There is usually a transient zone (TZ) with fluctuating MUA between the STN and SN. The ZI region tends to be variable. Each dot corresponds to an average MUA obtained from 10 seconds of MER. Data from subject #6, right STN.

Figure 4

Comparison IOM and QD. In this subject (#10, left STN), the dorsal STN borders obtained by both methods were identical at depth 2.3 mm above the anatomical target. The ventral border obtained by IOM was 1.6 mm below the anatomical target but according to the QD the microelectrode never left the STN and therefore the ventral border was assigned at the deepest MER at 2.8 mm below the anatomical target. ◄ = dorsal border using QD, ■ = ventral border using QD; = dorsal border using IOM, ↑ = ventral border using IOM. Shaded rectangle demarcates the STN derived from the IOM.

Figure 5

Comparison of optimal and suboptimal tracks. The anterior track gave the optimal length of the STN using both IOM and QD (4.6 versus 5.2 mm). The microelectrode at the central track entered the STN at a much deeper point (0.51 mm below the anatomical target) compared to the microelectrode in the anterior track (3.2 mm above the target). Only a small portion of the STN was captured by the central track. For descriptions of markers see legend to Figure 4. The shaded rectangle applies for the anterior track. Data from subject #6, left STN.

Figure 6

Comparison of two similar tracks. Both anterior and central tracks assign reasonable length to the STN (anterior track = 5.2 mm, central track = 3.98 mm). It was not straightforward using IOM, the golden standard, to decide which track was more optimal. QD shows that the microelectrode in the anterior track entered the STN first while the central track microelectrode entered the STN after advancing the drive deeper by 1.2 mm. Overlay of the MUA of both tracks confirmed that the longer portion of the STN was captured by an anterior track (“Best”). Note also that the MUA remains elevated at the end of recording at the electrode depth 3.52 mm, indicating that the microelectrode was still within the STN. Further advancement of the microelectrode was not done because the sufficient length of the STN has already been captured. For descriptions of markers see legend to Figure 4. Data from subject #8, left STN.

Figure 7

Example of a track that missed the target, subject #9, left STN. The anterior track missed the STN using both IOM and QD criteria. The microelectrode in the central track entered the STN and captured the optimal STN length (4.8 mm using IOM, 5.74 mm using QD). The dorsal borders were identical compared the IOM with the QD. According to the QD, the microelectrode never exited the STN. For descriptions of markers see legend to Figure 4. Data from subject #9, left STN.

Figure 8

Comparisons of the STN detection by IOM and QD. Each bar represents localization of the STN in one subject. The top of each bar corresponds to the STN entry (dorsal border) and the bottom of the bar corresponds to the exit from the STN (ventral border). The values above the anatomical target (at 0 mm) are positive, values below the target are negative. Only the best track is shown when simultaneously recording more than one track.