In Vivo Cortical Excitability Modulation in Major Depressive Disorder

Обзор

The pathophysiology of Major Depression Disorder (MDD) is unclear, with several theories for its neurobiological mechanisms. One possible explanation is the presence of altered neuroplasticity, which can be studied by Transcranial Magnetic Stimulation (TMS). Using TMS to study these mechanisms is performed by applying electromagnetic stimuli to the motor cortex, to obtain measures of temporary cortical excitability modulation. It is known that depressed patients with higher cortical modulation are more responsive to a TMS treatment course. However, it is unknown if there are differences in cortical modulation between depressed patients and healthy subjects. Our goal is to answer this question and contribute towards clarification of the neuroplasticity mechanisms underlying MDD. Accordingly, the investigators will access cortical excitability modulation measures in both depressed patients and healthy volunteers and compare their results. The investigators will also re-assess these measures after 6 weeks of antidepressant treatment. Finally, the investigators will study the association between cortical excitability measures and cognitive processes using an innovative cognitive task.

Подробное описание

Study objectives

The aim of this study is to evaluate differences in the modulation of cortical excitability by a repetitive Transcranial Magnetic Stimulation (rTMS) protocol between patients with Major Depressive Disorder (MDD) and healthy people. The investigators hypothesize that patients with MDD exhibit less modulation of cortical excitability when compared to healthy people.

In order to accomplish this goal the investigators will:

* Compare measures of cortical excitability between patients with MDD and healthy individuals; * Compare the degree of modulation of cortical excitability in motor cortex after the application of rTMS, between healthy individuals and patients with MDD; * Study the progression/evolution of these measures in the group of patients with MDD after 6 weeks of antidepressant treatment, while comparing patients that respond to treatment with patients with symptoms resistant to treatment; * Analyze the relationship between cortical excitability measures and cortical excitability modulation. Study participants will perform a psychophysical task, on a computer game, in order to evaluate certain cognitive processes and understand if there are differences in performance between patients with depression and healthy subjects.

Data Collection

* Clinical assessment: Clinical interview will be performed with help of psychiatric, psychological and cognitive psychometric instruments (self-report questionnaires and structured interviews) to assess the participants' health. * Behavioural assessment: Participants will perform a psychophysical task in the form of a computer game. * Neurophysiological evaluation: protocol for assessing excitability and excitability modulation of the motor cortex by EMT and EMTr (ETBi).

Procedures

The participants recruited for the present project will be patients who are already being treated by health professionals at the Champalimaud Clinical Center, as well as healthy individuals, recruited from the nearby community. One cohort will include patients with active/symptomatic MDD and a second cohort will include patients with MDD in remission that are still in treatment. The third cohort will include a control group of healthy individuals. After they are referred to participate in this study, and if consent to participate is collected, they will be assessed to confirm their eligibility and group allocation will be performed. The study participants from all three observational groups will be submitted to (1) full clinical information assessment, (2) will be asked to perform a psychophysical task, i.e. a computer game. Finally, (3) the neurophysiological evaluation protocol will be applied. This neurophysiological evaluation protocol will be performed in two visits separated by at least 48h. This will make it possible to assess cortical excitability measures in both hemispheres independently and safely, allowing the acquisition of interhemispheric asymmetry measures. The order in which the cerebral hemispheres will be assessed will be randomized between participants. The first visit should take no longer than 120 minutes, and the second will last less than 45 minutes. Participants in the study will also be asked to come for a second study visit, to the Champalimaud Clinical Center, approximately 6 weeks after the first visit, the same study protocol will be repeated, in two consecutive sessions with the same procedures.Participants will not be rewarded monetarily; they will be supported for travel to the Clinical Center that may be necessary outside their individual clinical follow-up

Вмешательства

• Другое No intervention/expousure
  No interventions/expousure since this is an observational study.

Первичные конечные точки

• Baseline left cortical excitability modulation [Срок оценки: Baseline]

Вторичные конечные точки (1)

• Left cortical excitability modulation changes according to treatment response [Срок оценки: Baseline and after ~6 weeks.]

Критерии участия

Inclusion criteria (clinical groups):

1\. Diagnosis of major depressive episode or disorder as provided in the Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5) (American Psychiatric Association. 2013).

Exclusion criteria (clinical groups):

• Moderate to severe suicide risk;
• Known personal history of bipolar disorder or psychotic disorder;
• Alcohol or other substance abuse and/or dependence;
• Developmental disorder;
• Dementia;
• Presence of uncontrolled active medical illness;
• Known structural lesion of the central nervous system;
• Electrical or metallic brain implants;
• Cardiac implants;
• Epilepsy;
• Active use of medication known to cause seizures;
• Pregnancy;
• Breastfeeding.

For the healthy control group, participants will also be recruited at the Champalimaud Clinical Center, by advertisement in places of public circulation. The recruitment of this population will be done in order to generate a pairing with both clinical groups in terms of age and sex. The same exclusion criteria will be applied, as well as the presence of any history of neuropsychiatric disease. The total number of participants for this study will be approximately 90 volunteers. Exclusion criteria will be assessed through self-report and/or MINI.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Португалия · 1 центр

• Champalimaud Foundation — Lisbon

Публикации

• Benussi A, Di Lorenzo F, Dell'Era V, Cosseddu M, Alberici A, Caratozzolo S, Cotelli MS, Micheli A, Rozzini L, Depari A, Flammini A, Ponzo V, Martorana A, Caltagirone C, Padovani A, Koch G, Borroni B. Transcranial magnetic stimulation distinguishes Alzheimer disease from frontotemporal dementia. Neurology. 2017 Aug 15;89(7):665-672. doi: 10.1212/WNL.0000000000004232. Epub 2017 Jul 26. PMID 28747446
• Blumberger DM, Vila-Rodriguez F, Thorpe KE, Feffer K, Noda Y, Giacobbe P, Knyahnytska Y, Kennedy SH, Lam RW, Daskalakis ZJ, Downar J. Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial. Lancet. 2018 Apr 28;391(10131):1683-1692. doi: 10.1016/S0140-6736(18)30295-2. Epub 2018 Apr 26. PMID 29726344
• Chang WH, Fried PJ, Saxena S, Jannati A, Gomes-Osman J, Kim YH, Pascual-Leone A. Optimal number of pulses as outcome measures of neuronavigated transcranial magnetic stimulation. Clin Neurophysiol. 2016 Aug;127(8):2892-2897. doi: 10.1016/j.clinph.2016.04.001. Epub 2016 Apr 12. PMID 27156431
• Chung SW, Hill AT, Rogasch NC, Hoy KE, Fitzgerald PB. Use of theta-burst stimulation in changing excitability of motor cortex: A systematic review and meta-analysis. Neurosci Biobehav Rev. 2016 Apr;63:43-64. doi: 10.1016/j.neubiorev.2016.01.008. Epub 2016 Feb 3. PMID 26850210
• Cincotta M, Giovannelli F, Borgheresi A, Balestrieri F, Toscani L, Zaccara G, Carducci F, Viggiano MP, Rossi S. Optically tracked neuronavigation increases the stability of hand-held focal coil positioning: evidence from "transcranial" magnetic stimulation-induced electrical field measurements. Brain Stimul. 2010 Apr;3(2):119-23. doi: 10.1016/j.brs.2010.01.001. Epub 2010 Jan 29. PMID 20633439
• Concerto C, Lanza G, Cantone M, Pennisi M, Giordano D, Spampinato C, Ricceri R, Pennisi G, Aguglia E, Bella R. Different patterns of cortical excitability in major depression and vascular depression: a transcranial magnetic stimulation study. BMC Psychiatry. 2013 Nov 9;13:300. doi: 10.1186/1471-244X-13-300. PMID 24206945
• Daskalakis ZJ, Farzan F, Barr MS, Maller JJ, Chen R, Fitzgerald PB. Long-interval cortical inhibition from the dorsolateral prefrontal cortex: a TMS-EEG study. Neuropsychopharmacology. 2008 Nov;33(12):2860-9. doi: 10.1038/npp.2008.22. Epub 2008 Mar 5. PMID 18322469
• Fitzgerald, Paul B., and Z. Jeff Daskalakis. Repetitive Transcranial Magnetic Stimulation Treatment for Depressive Disorders: A Practical Guide. Heidelberg: Springer, 2013.

Идентификаторы

NCT: NCT05441969 · PDM-TMS

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗