{"doi":"10.1002/mds.29409","title":"Subthalamic Physiology in Genetic Subtypes of Parkinson's Disease","abstract":"We read with interest the recent article by Weill et al.1 The authors collected local field potential (LFP) activity during implantation of subthalamic nucleus (STN) electrodes. They compared β-activity in genetic subtypes and idiopathic PD (iPD). No differences were found in β-activity, and the authors conclude that, in the future, similar adaptive deep brain stimulation (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 preoperative 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 based on genotype do not exist. In the present study, the authors examined only β-activity. Though β-power can be used for adaptive DBS, low-frequency (LF)/β-power ratio may be advantageous over β-activity alone.2 Combining peak β-power, which mainly reflects the dorsal STN, with LF activity (4–12 Hz), which has a more diffuse signal,3 allows for a broader representation of STN 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 the asymmetry of β-activity among 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 between β-power within the STN and the amount of β-power before entering the STN. In contrast, we selected the contact with the highest β-peak and then calculated β-ratio as the relationship between the area under the frequency with the highest β-power ±2 Hz 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, whereas 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 were collected using a single recording system, whereas the authors in the present study used two different systems in a nonrandom manner, which was not considered in their statistical analysis. The lack of statistical differences does 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 based on genotype exist, before concluding that a uniform approach to adaptive DBS should be employed. (1) Design and execution, (2) writing of the initial draft, and (3) editing of the final version of the manuscript. G.D.P.: 1–3 F.J.D., J.L.S., M.J.M., M.A., S.S., L.V.M., D.M.C.: 3 Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.","journal":"Movement Disorders","year":2023,"id":409697,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9526,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":491026,"name":"Fabian J. David","orcid":"0000-0001-7780-788X","position":1,"is_corresponding":false},{"id":1189239,"name":"Jay L. Shils","orcid":"0000-0002-2284-3530","position":2,"is_corresponding":false},{"id":491027,"name":"Miranda J. Munoz","orcid":"0000-0002-3782-6530","position":3,"is_corresponding":false},{"id":849832,"name":"Mitra Afshari","orcid":"0000-0003-4803-953X","position":4,"is_corresponding":false},{"id":542253,"name":"Sepehr Sani","orcid":"0000-0002-1737-5269","position":5,"is_corresponding":false},{"id":542254,"name":"Leo Verhagen Metman","orcid":"0000-0002-5503-1475","position":6,"is_corresponding":false},{"id":289902,"name":"Daniel M. Corcos","orcid":"0000-0001-7440-6458","position":7,"is_corresponding":false},{"id":446789,"name":"Gian Pal","orcid":"0000-0003-1048-6182","position":0,"is_corresponding":true}],"reference_count":7,"raw_metadata":null,"created_at":"2026-07-19T01:21:27.199694Z","pmid":"37475610","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}