We read with interest the recent article by Weill et al.1 The authors collected local field potential activity during implantation of subthalamic nucleus (STN) electrodes. They compared beta (β) activity in genetic subtypes and idiopathic PD (iPD). No differences in β-activity were found and the authors conclude that, in the future, similar adaptive DBS algorithms would be applicable across groups.
This study’s strengths include examination of different PD genetic subtypes and robust electrophysiological data. However, we suggest the results should be interpreted cautiously. Our understanding of the role of genetics as part of the pre-operative DBS process is still in its nascent stages and further work examining electrophysiological and other biomarkers is needed before we can conclude that group differences do not exist based on genotype.
In the present study, the authors examined only β-activity. Though β-power can be used for adaptive DBS, low frequency (LF)/beta power ratio may be advantageous over β-activity alone.2 Combining peak β-power, which mainly reflects dorsal STN, with LF activity (4–12 Hz), which has a more diffuse signal,3 allows for broader representation of STN local field potential (LFP) activity, which may be beneficial for adaptive DBS. Importantly, increases in LFP activity in delta (1–4 Hz) and theta (4–7 Hz) bands have been implicated in cognitive control.4 Changes in delta and theta activity have yet to be examined in glucocerebrosidase (GBA1) mutation carriers, a population at high risk for cognitive decline.5 Other genetic PD subtypes may have phenotypic features pertinent to DBS outcomes, with electrophysiologic correlates, which require examination.
The authors also examined asymmetry of β-activity amongst the groups by calculating an asymmetry index (AI) and found no differences between GBA1 and iPD patients which they conclude is in contrast to our previous report.6 Critical differences between the two studies make it difficult to draw this conclusion. The authors calculated β-ratio as the relationship of β-power within STN compared with the amount of β-power prior to entering STN. In contrast, we selected the contact with the highest β-peak, then calculated β-ratio as the relationship between the area under the frequency with the highest β-power +/− 2Hz, and the area under the entire β-band. These two methodologies of calculating β-ratio are fundamentally different, so comparing AI from these studies is problematic. The authors examined GBA1 subjects with various mutations, while all our GBA1 subjects carried the E326K variant. This is an important distinction as different mutation types alter glucocerebrosidase enzymatic activity to varying degrees,5 which may have differential neurophysiological effects. Our data was collected using a single recording system, while the authors in the present study used two different systems in a non-random fashion, which was not considered in their statistical analysis.
The lack of statistical differences do not necessarily mean that the groups were similar.7 Continued work is needed to understand the electrophysiologic basis of not only motor, but also cognitive and other non-motor symptoms, to determine if group differences exist based on genotype, before concluding that a uniform approach to adaptive DBS should be employed.
Financial Disclosures:
GDP received grant support from National Institute of Neurological Disorders and Stroke, and consulting fees from Guidepoint, Kyowa Kirin. FJD and MJM received grant support from NIH. JLS, nothing to report. MA received grant support from Abbott, PSG, NIH. SS received grant support from NIH, Medtronic, Abbott, and Boston Scientific. SS consults for Insightec and received royalties from Globus Medical. LVM received grant support from NIH, consulting fees from AbbVie, Abbott, Avion and Clinical Trial Agreement-related salary support from Medtronic, Abbott, Boston Sci, AbbVie, Neuroderm. DMC received grant support from NIH and Michael J. Fox and receives lecture and reviewer fees from NIH.
Funding sources: National Institute of Neurological Disorders and Stroke (K23-NS097625, GDP (PI); R01NS092950, DMC (PI); T32 NS047987, F31 NS120695, MJM).
References:
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