Autor(es): Mendonça, Marcelo ; Cotovio, Gonçalo ; Barbosa, Raquel ; Grunho, Miguel ; Oliveira-Maia, AJ
Data: 2022
Identificador Persistente: http://hdl.handle.net/10362/142071
Origem: Repositório Institucional da UNL
Assunto(s): connectivity; deep brain stimulation; Holmes tremor; movement disorders; n-of-1 trials; Neuropsychology and Physiological Psychology; Neurology; Psychiatry and Mental health; Biological Psychiatry; Behavioral Neuroscience; SDG 3 - Good Health and Well-being
Funding Information: AJO-M was national coordinator for Portugal of a non-interventional study (EDMS-ERI-143085581, 4.0) to characterize a Treatment-Resistant Depression Cohort in Europe, sponsored by Janssen-Cilag, Ltd. (2019–2020), is recipient of a grant from Schuhfried GmbH for norming and validation of cognitive tests, and is national coordinator for Portugal of trials of psilocybin therapy for treatment-resistant depression, sponsored by Compass Pathways, Ltd. (EudraCT number 2017-003288-36 and 2020-001348-25), and of esketamine for treatment-resistant depression, sponsored by Janssen-Cilag, Ltd. (EudraCT NUMBER: 2019-002992-33). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Funding Information: GC was supported by Fundação para a Ciência e Tecnologia (FCT) through a Ph.D. Scholarship (SFRH/BD/130210/2017). RB was supported by Fundação para a Ciência e Tecnologia (FCT) through a Ph.D. Scholarship (SFRH/BD/143797/2019) and Prémio João Lobo Antunes by Santa Casa da Misericórdia de Lisboa. AJO-M was supported by grant FCT-PTDC/MEC-PSQ/30302/2017-IC&DT-LISBOA-01-0145-FEDER, funded by national funds from FCT/MCTES and co-funded by FEDER, under the Partnership Agreement Lisboa 2020 – Programa Operacional Regional de Lisboa. GC and AJO-M were supported by grant FCT-PTDC/MED-NEU/31331/2017, funded by FCT/MCTES. MM and AJOM were supported by grant EurDyscover – EJPRD19-135, funded by FCT/MCTES through the European Joint Programme for Rare Disease. MM was supported by grant UIBD/04443/2020, funded by FCT/MCTES. Funding Information: GC was supported by Fundação para a Ciência e Tecnologia (FCT) through a Ph.D. Scholarship (SFRH/BD/130210/2017). RB was supported by Fundação para a Ciência e Tecnologia (FCT) through a Ph.D. Scholarship (SFRH/BD/143797/2019) and Prémio João Lobo Antunes by Santa Casa da Misericórdia de Lisboa. AJO-M was supported by grant FCT-PTDC/MEC-PSQ/30302/2017-IC&DT-LISBOA-01-0145-FEDER, funded by national funds from FCT/MCTES and co-funded by FEDER, under the Partnership Agreement Lisboa 2020 – Programa Operacional Regional de Lisboa. GC and AJO-M were supported by grant FCT-PTDC/MED-NEU/31331/2017, funded by FCT/MCTES. MM and AJOM were supported by grant EurDyscover – EJPRD19-135, funded by FCT/MCTES through the European Joint Programme for Rare Disease. MM was supported by grant UIBD/04443/2020, funded by FCT/MCTES. Publisher Copyright: Copyright © 2022 Mendonça, Cotovio, Barbosa, Grunho and Oliveira-Maia.
Deep brain stimulation (DBS) is part of state-of-the-art treatment for medically refractory Parkinson’s disease, essential tremor or primary dystonia. However, there are multiple movement disorders that present after a static brain lesion and that are frequently refractory to medical treatment. Using Holmes tremor (HT) as an example, we discuss the effectiveness of currently available treatments and, performing simulations using a Markov Chain approach, propose that DBS with iterative parameter optimization is expected to be more effective than an approach based on sequential trials of pharmacological agents. Since, in DBS studies for HT, the thalamus is a frequently chosen target, using data from previous studies of lesion connectivity mapping in HT, we compared the connectivity of thalamic and non-thalamic targets with a proxy of the HT network, and found a significantly higher connectivity of thalamic DBS targets in HT. The understanding of brain networks provided by analysis of functional connectivity may thus provide an informed framework for proper surgical targeting of individual patients. Based on these findings, we argue that there is an ethical imperative to at least consider surgical options in patients with uncommon movement disorders, while simultaneously providing consistent information regarding the expected effectiveness and risks, even in a scenario of surgical-risk aversion. An approach based on n-of-1 DBS trials may ultimately significantly improve outcomes while informing on optimal therapeutic targets and parameter settings for HT and other disabling and rare movement disorders.
