Several neurological diseases are accompanied by rhythmic oscillatory dysfunctions in various frequency ranges and disturbed cross-frequency relationships on regional, interregional, and whole brain levels. Knowledge of these disease-specific oscillopathies is important mainly in the context of deep brain stimulation (DBS) therapy. Electrophysiological biomarkers have been used as input signals for adaptive DBS (aDBS) as well as preoperative outcome predictors. As movement disorders, particularly Parkinson's disease (PD), are among the most frequent DBS indications, the current research of DBS is the most advanced in the movement disorders field. We reviewed the literature published mainly between 2010 and 2020 to identify the most important findings concerning the current evolution of electrophysiological biomarkers in DBS and to address future challenges for prospective research.

Central European Institute of Technology Brain and Mind Research Program Masaryk University Brno Czech Republic

Movement Disorders Center 1st Department of Neurology Masaryk University School of Medicine St Anne's Hospital Pekařská 53 656 91 Brno Czech Republic

Zobrazit více v PubMed

Alegre M, Alonso-Frech F, Rodríguez-Oroz MC, Guridi J, Zamarbide I, Valencia M, Manrique M, Obeso JA, Artieda J (2005) Movement-related changes in oscillatory activity in the human subthalamic nucleus: ipsilateral vs. contralateral movements. Eur J Neurosci 22:2315–2324 PubMed DOI

Androulidakis AG, Kühn AA, Chen CC, Blomstedt P, Kempf F, Kupsch A, Schneider GH, Doyle L, Dowsey-Limousin P, Hariz MI, Brown P (2007) Dopaminergic therapy promotes lateralized motor activity in the subthalamic area in Parkinson’s disease. Brain 130(Pt 2):457–468 PubMed DOI

Barow E, Neumann WJ, Brücke C, Huebl J, Horn A, Brown P et al (2014) Deep brain stimulation suppresses pallidal low frequency activity in patients with phasic dystonic movements. Brain 137(Pt 11):3012–3024 PubMed DOI

Benabid AL, Chabardes S, Mitrofanis J, Pollak P (2009) Deep brain stimulation of the subthalamic nucleus for the treatment of Parkinson’s disease. Lancet Neurol 8(1):67–81 PubMed DOI

Bočková M, Rektor I (2019) Impairment of brain functions in Parkinson’s disease reflected by alterations in neural connectivity in EEG studies: a viewpoint. Clin Neurophysiol 130(2):239–247 PubMed DOI

Bočková M, Chládek J, Jurák P, Halámek J, Rapcsak SZ, Baláž M, Chrastina J, Rektor I (2017) Oscillatory reactivity to effortful cognitive processing in the subthalamic nucleus and internal pallidum: a depth electrode EEG study. J Neural Transm 124(7):841–852 PubMed DOI

Bočková M, Lamoš L, Klimeš P, Jurák P, Halámek J, Goldemundová S, Baláž M, Rektor I (2020) Suboptimal response to STN-DBS in Parkinson’s disease can be identified via reaction times in a motor cognitive paradigm. J Neural Transm 127(12):1579–1588 PubMed DOI

Bonanni L, Thomas A, Tiraboschi P, Perfetti B, Varanese S, Onofrj M (2008) EEG comparisons in early Alzheimer’s disease, dementia with Lewy bodies and Parkinson’s disease with dementia patients with a 2 year follow-up. Brain 131(Pt 3):690–705 PubMed DOI

Bouthour W, Mégevand P, Donoghue J, Lüscher C, Birbaumer N, Krack P (2019) Biomarkers for closed-loop deep brain stimulation in Parkinson disease and beyond. Nat Rev Neurol 15(6):343–352 PubMed DOI

Brown P (2006) Bad oscillations in Parkinson’s disease. J Neural Transm Suppl 70:27–30

Cagnan H, Brittain JS, Little S, Foltynie T, Limousin P, Zrinzo L et al (2013) Phase dependent modulation of tremor amplitude in essential tremor through thalamic stimulation. Brain 136:3062–3075 PubMed DOI PMC

Cagnan H, Pedrosa D, Little S, Pogosyan A, Cheeran B, Aziz T et al (2017) Stimulating at the right time: phase-specific deep brain stimulation. Brain 140(1):132–145 PubMed DOI PMC

Cagnan H, Denison T, McIntyre C, Brown P (2019) Emerging technologies for improved deep brain stimulation. Nat Biotechnol 37(9):1024–1033 PubMed DOI PMC

Castaño-Candamil S, Piroth T, Reinacher P, Sajonz B, Coenen VA, Tangermann M (2020) Identifying controllable cortical neural markers with machine learning for adaptive deep brain stimulation in Parkinson’s disease. Neuroimage Clin. https://doi.org/10.1016/j.nicl.2020.102376 PubMed DOI PMC

Chen CC, Hsu YT, Chan HL, Chiou SM, Tu PH, Lee ST et al (2010) Complexity of subthalamic 13–35 Hz oscillatory activity directly correlates with clinical impairment in patients with Parkinson’s disease. Exp Neurol 224(1):234–240 PubMed DOI PMC

Deffains M, Bergman H (2019) Parkinsonism-related β oscillations in the primate basal ganglia networks—recent advances and clinical implications. Parkinsonism Relat Disord 59:2–8 PubMed DOI PMC

Deffains M, Iskhakova L, Katabi S, Israel Z, Bergman H (2018) Longer β oscillatory episodes reliably identify pathological subthalamic activity in Parkinsonism. Mov Disord 33(10):1609–1618 PubMed DOI

DeLong MR, Huang KT, Gallis J, Lokhnygina Y, Parente B, Hickey P et al (2014) Effect of advancing age on outcomes of deep brain stimulation for Parkinson disease. JAMA Neurol 71(10):1290–1295 PubMed DOI

DiMarzio M, Madhavan R, Joel S, Hancu I, Fiveland E, Prusik J et al (2020) Use of functional magnetic resonance imaging to assess how motor phenotypes of Parkinson’s Disease respond to deep brain stimulation. Neuromodulation 23(4):515–524 PubMed DOI

Ferreira D, Jelic V, Cavallin L, Oeksengaard AR, Snaedal J, Høgh P et al (2016) Electroencephalography is a good complement to currently established dementia biomarkers. Dement Geriatr Cogn Disord 42(1–2):80–92 PubMed DOI PMC

French Stimulation dans Trouble Obsessionnel Compulsif (STOC) Study Group, Welter ML, Burbaud P, Fernandez-Vidal S, Bardinet E, Coste J, Piallat B et al (2011) Basal ganglia dysfunction in OCD: subthalamic neuronal activity correlates with symptoms severity and predicts high-frequency stimulation efficacy. Transl Psychiatry. https://doi.org/10.1038/tp.2011.5 DOI

Geraedts VJ, Koch M, Contarino MF et al (2021) Machine learning for automated EEG-based biomarkers of cognitive impairment during deep brain stimulation screening in patients with Parkinson’s disease. Clin Neurophysiol 132(5):1041–1048 PubMed DOI PMC

Habets JGV, Heijmans M, Kuijf ML, Janssen MLF, Temel Y, Kubben PL (2018) An update on adaptive deep brain stimulation in Parkinson’s disease. Mov Disord 33(12):1834–1843. https://doi.org/10.1002/mds.115 PubMed DOI PMC

Herron JA, Thompson MC, Brown T, Chizeck HJ, Ojemann JG, Ko AL (2017) Chronic electrocorticography for sensing movement intention and closed-loop deep brain stimulation with wearable sensors in an essential tremor patient. J Neurosurg 127(3):580–587 PubMed DOI PMC

Herz DM, Little S, Pedrosa DJ, Tinkhauser G, Cheeran B, Foltynie T et al (2018) Mechanisms Underlying decision-making as revealed by deep-brain stimulation in patients with Parkinson’s disease. Curr Biol 28(8):1169-1178.e6 PubMed DOI PMC

Horn A, Reich M, Vorwerk J, Li N, Wenzel G, Fang Q et al (2017) Connectivity predicts deep brain stimulation outcome in Parkinson disease. Ann Neurol 82(1):67–78 PubMed DOI PMC

Kühn AA, Kupsch A, Schneider GH, Brown P (2006) Reduction in subthalamic 8–35 Hz oscillatory activity correlates with clinical improvement in Parkinson’s disease. Eur J Neurosci 23(7):1956–1960 PubMed DOI PMC

Little S, Pogosyan A, Neal S, Zavala B, Zrinzo L, Hariz M et al (2013) Adaptive deep brain stimulation in advanced Parkinson disease. Ann Neurol 74(3):449–457 PubMed DOI PMC

Little S, Beudel M, Zrinzo L, Foltynie T, Limousin P, Hariz M et al (2016a) Bilateral adaptive deep brain stimulation is effective in Parkinson’s disease. J Neurol Neurosurg Psychiatry 87(7):717–721 PubMed DOI PMC

Little S, Tripoliti E, Beudel M, Pogosyan A, Cagnan H, Herz D et al (2016b) Adaptive deep brain stimulation for Parkinson’s disease demonstrates reduced speech side effects compared to conventional stimulation in the acute setting. J Neurol Neurosurg Psychiatry 87(12):1388–1389 PubMed DOI PMC

López-Azcárate J, Tainta M, Rodríguez-Oroz MC, Valencia M, González R, Guridi J, Iriarte J, Obeso JA, Artieda J, Alegre M (2010) Coupling between beta and high-frequency activity in the human subthalamic nucleus may be a pathophysiological mechanism in Parkinson’s disease. J Neurosci 30(19):6667–6677 PubMed DOI PMC

Lozano AM, Lipsman N, Bergman H, Brown P, Chabardes S, Chang JW et al (2019) Deep brain stimulation: current challenges and future directions. Nat Rev Neurol 15(3):148–160 PubMed DOI PMC

Markser A, Maier F, Lewis CJ, Dembek TA, Pedrosa D, Eggers C et al (2015) Deep brain stimulation and cognitive decline in Parkinson’s disease: the predictive value of electroencephalography. J Neurol 262:2275–2284 PubMed DOI

McIntyre CC, Savasta M, Kerkerian-Le Goff L, Vitek JL (2004) Uncovering the mechanism(s) of action of deep brain stimulation: activation, inhibition, or both. Clin Neurophysiol 115(6):1239–1248 PubMed DOI

Meidahl AC, Moll CKE, van Wijk BCM, Gulberti A, Tinkhauser G, Westphal M et al (2019) Synchronised spiking activity underlies phase amplitude coupling in the subthalamic nucleus of Parkinson’s disease patients. Neurobiol Dis 127:101–113 PubMed DOI PMC

Middlebrooks EH, Grewal SS, Stead M, Lundstrom BN, Worrell GA and Van Gompel JJ (2018) Differences in functional connectivity profiles as a predictor of response to anterior thalamic nucleus deep brain stimulation for epilepsy: a hypothesis for the mechanism of action and a potential biomarker for outcomes. Neurosurg Focus 45(2):E7

Molina R, Okun MS, Shute JB, Opri E, Rossi PJ, Martinez-Ramirez D et al (2018) Report of a patient undergoing chronic responsive deep brain stimulation for Tourette syndrome: proof of concept. J Neurosurg 129(2):308–314 PubMed DOI

Moll CKE, Engel AK (2017) Phase matters: cancelling pathological tremor by adaptive deep brain stimulation. Brain 140(1):5–8 PubMed DOI

Neumann WJ, Jha A, Bock A, Huebl J, Horn A, Schneider GH et al (2015) Cortico-pallidal oscillatory connectivity in patients with dystonia. Brain 138(Pt 7):1894–1906 PubMed DOI

Neumann WJ, Horn A, Ewert S, Huebl J, Brücke C, Slentz C, Schneider GH, Kühn AA (2017) A localized pallidal physiomarker in cervical dystonia. Ann Neurol 82(6):912–924 PubMed DOI

Neumann WJ, Huebl J, Brücke C, Lofredi R, Horn A, Saryyeva A et al (2018) Pallidal and thalamic neural oscillatory patterns in tourette’s syndrome. Ann Neurol 84(4):505–514 PubMed DOI

Neumann WJ, Turner RS, Blankertz B, Mitchell T, Kühn AA, Richardson RM (2019) Toward Electrophysiology-based intelligent adaptive deep brain stimulation for movement disorders. Neurotherapeutics 16(1):105–118 PubMed DOI PMC

Onofrj M, Espay AJ, Bonanni L, Delli Pizzi S, Sensi SL (2019) Hallucinations, somatic-functional disorders of PD-DLB as expressions of thalamic dysfunction. Mov Disord 34(8):1100–1111 PubMed DOI PMC

Oswal A, Litvak V, Brücke C, Huebl J, Schneider GH, Kühn AA, Brown P (2013) Cognitive factors modulate activity within the human subthalamic nucleus during voluntary movement in Parkinson’s disease. J Neurosci 33:15815–15826 PubMed DOI PMC

Oswal A, Beudel M, Zrinzo L, Limousin P, Hariz M, Foltynie T, Litvak V, Brown P et al (2016) Deep brain stimulation modulates synchrony within spatially and spectrally distinct resting state networks in Parkinson’s disease. Brain 139(Pt 5):1482–1496 PubMed DOI PMC

Piña-Fuentes D, Beudel M, Little S, van Zijl J, Elting JW, Oterdoom DLM et al (2018) Toward adaptive deep brain stimulation for dystonia. Neurosurg Focus 45(2):E3 PubMed DOI

Rappel P, Marmor O, Bick AS, Arkadir D, Linetsky E, Castrioto A et al (2018) Subthalamic theta activity: a novel human subcortical biomarker for obsessive compulsive disorder. Transl Psychiatry. https://doi.org/10.1038/s41398-018-0165-z PubMed DOI PMC

Rosa M, Arlotti M, Ardolino G, Cogiamanian F, Marceglia S, Di Fonzo A et al (2015) Adaptive deep brain stimulation in a freely moving Parkinsonian patient. Mov Disord 30(7):1003–1005 PubMed DOI PMC

Schuepbach WMM, Rau J, Knudsen K, Volkmann J, Krack P, Timmermann L et al (2013) Neurostimulation for Parkinson’s disease with early motor complications. N Engl J Med 368(7):610–622 PubMed DOI

Sherdil A, Chabardès S, David O, Piallat B (2020) Coherence between the hippocampus and anterior thalamic nucleus as a tool to improve the effect of neurostimulation in temporal lobe epilepsy: An experimental study. Brain Stimul 13(6):1678–1686

Swann NC, de Hemptinne C, Thompson MC, Miocinovic S, Miller AM, Gilron R et al (2018) Adaptive deep brain stimulation for Parkinson’s disease using motor cortex sensing. J Neural Eng. https://doi.org/10.1088/1741-2552/aabc9b PubMed DOI PMC

Tan H, Debarros J, He S, Pogosyan A, Aziz TZ, Huang Y et al (2019) Decoding voluntary movements and postural tremor based on thalamic LFPs as a basis for closed-loop stimulation for essential tremor. Brain Stimul 12(4):858–867 PubMed DOI PMC

Telkes I, Viswanathan A, Jimenez-Shahed J, Abosch A, Ozturk M, Gupte A, Jankovic J, Ince NF (2018) Local field potentials of subthalamic nucleus contain electrophysiological footprints of motor subtypes of Parkinson’s disease. Proc Natl Acad Sci U S A 115(36):E8567–E8576 PubMed DOI PMC

Tinkhauser G, Pogosyan A, Debove I, Nowacki A, Shah SA, Seidel K et al (2018) Directional local field potentials: a tool to optimize deep brain stimulation. Mov Disord 33(1):159–164 PubMed DOI PMC

Yakufujiang M, Higuchi Y, Aoyagi K, Yamamoto T, Abe M, Okahara Y et al (2019) Predictive potential of preoperative electroencephalogram for neuropsychological change following subthalamic nucleus deep brain stimulation in Parkinson’s disease. Acta Neurochir 161(10):2049–2058 PubMed DOI PMC

The effect of deep brain stimulation in Parkinson's disease reflected in EEG microstates