A pilot randomized sham controlled trial of bilateral iTBS for depression and executive function in older adults
Abstract
Introduction: Executive function deficits (EFD) in late life depression (LLD) are associated with poor outcomes. Dysfunction of the cognitive control network (CCN) has been posited in the pathophysiology of LLD with EFD. Methods: Seventeen older adults with depression and EFD were randomized to iTBS or sham for 6 weeks. Intervention was delivered bilaterally using a recognized connectivity target. Results: A total of 89% (17/19) participants completed all study procedures. No serious adverse events occurred. Pre to post‐intervention change in mean Montgomery‐Asberg‐depression scores was not different between iTBS or sham, p = 0.33. No significant group‐by‐time interaction for Montgomery‐Asberg Depression rating scale scores (F 3, 44 = 0.51; p = 0.67) was found. No significant differences were seen in the effects of time between the two groups on executive measures: Flanker scores (F 1, 14 = 0.02, p = 0.88), Dimensional‐change‐card‐sort scores F 1, 14 = 0.25, p = 0.63, and working memory scores (F 1, 14 = 0.98, p = 0.34). The Group‐by‐time interaction effect for functional connectivity (FC) within the Fronto‐parietal‐network was not significant (F 1, 14 = 0.36, p = 0.56). No significant difference in the effect‐of‐time between the two groups was found on FC within the Cingulo‐opercular‐network (F 1, 14 = 0, p = 0.98). Conclusion: Bilateral iTBS is feasible in LLD. Preliminary results are unsupportive of efficacy on depression, executive function or target engagement of the CCN. A future Randomized clinical trial requires a larger sample size with stratification of cognitive and executive variables and refinement in the target engagement.
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The 2023 pilot RCT did not provide evidence in favor of the effectiveness of bilateral iTBS as a treatment for depression or EFD in the elderly.
“Unfortunately, this pilot study did not provide evidence in favor of the effectiveness of bilateral iTBS as a treatment for depression or EFD in the elderly.”
From Can Intermittent Theta-Burst Stimulation of Dorsolateral Prefrontal Cortex Relieve Executive Dysfunction in Patients With Late-Life Depression? (2024) · cites this paper as [17]
Other rTMS studies in late-life depression found no significant changes in cognitive function after treatment.
“However, other studies found no significant changes in cognitive function after treatment.”
Four studies included measures of attention and working memory.
“Four studies (Cole et al., 2020;Cristancho et al., 2023;Fitzgerald et al., 2020;Holczer et al., 2021) included measures of attention and working memory.”
From Neurocognitive effects of theta burst stimulation for treatment-resistant depression in adults: A systematic review and recommendations for future research (2025) · cites this paper as Cristancho et al., 2023
Neither Cristancho et al. (2020) nor Cristancho et al. (2023) found significant results related to the DCCS.
“Neither study found significant results related to the DCCS”
From Neurocognitive effects of theta burst stimulation for treatment-resistant depression in adults: A systematic review and recommendations for future research (2025) · cites this paper as Cristancho et al., 2023
A follow-up study by Cristancho et al. (2023) and a study by Blumberger et al. (2022) failed to replicate the earlier finding of significant improvement on the Flanker Inhibitory Control and Attention Test.
“but a follow up study by Cristancho et al. (2023) and a study by Blumberger et al. (2022) failed to replicate that earlier finding.”
From Neurocognitive effects of theta burst stimulation for treatment-resistant depression in adults: A systematic review and recommendations for future research (2025) · cites this paper as Cristancho et al., 2023
Cristancho et al. (2020) and Cristancho et al. (2023) assessed the impact of TBS on performance on the Frontal Systems Behavioral Scale executive subscale and the NIH Toolbox Dimensional Change Card Sort.
“Cristancho et al. (2020) and Cristancho et al. (2023) also assessed the impact of TBS on performance on the Frontal Systems Behavioral Scale (FrSBe) executive subscale and the NIH Toolbox Dimensional Change Card Sort (DCCS).”
From Neurocognitive effects of theta burst stimulation for treatment-resistant depression in adults: A systematic review and recommendations for future research (2025) · cites this paper as Cristancho et al., 2023
A follow-up study by Cristancho et al. (2023) failed to replicate the finding of a significant decrease in dysexecutive-behavior.
“a follow-up study by Cristancho et al. (2023) failed to replicate that finding.”
From Neurocognitive effects of theta burst stimulation for treatment-resistant depression in adults: A systematic review and recommendations for future research (2025) · cites this paper as Cristancho et al., 2023
NIH Toolbox cognitive measures were used in three studies.
“The NIH Toolbox cognitive measures were also used in three studies (Blumberger et al., 2022;Cristancho et al., 2020;Cristancho et al., 2023).”
From Neurocognitive effects of theta burst stimulation for treatment-resistant depression in adults: A systematic review and recommendations for future research (2025) · cites this paper as Cristancho et al., 2023
Cristancho et al. (2023) found no significant change in working memory within or between groups between timepoints using the NIH Toolbox List Sorting Working Memory Test.
“Cristancho et al. (2023) found no significant change in working memory within or between groups between timepoints using the NIH Toolbox List Sorting Working Memory Test.”
From Neurocognitive effects of theta burst stimulation for treatment-resistant depression in adults: A systematic review and recommendations for future research (2025) · cites this paper as Cristancho et al., 2023
Cristancho et al. (2023) found no within- or between-group differences on the NIH Toolbox Crystallized Composite score.
“Cristancho et al. (2023) used the NIH Toolbox cognitive battery Crystallized Composite score (Oral Reading Recognition and Picture Vocabulary) to measure crystallized intelligence and found no within-or between-group differences.”
From Neurocognitive effects of theta burst stimulation for treatment-resistant depression in adults: A systematic review and recommendations for future research (2025) · cites this paper as Cristancho et al., 2023
Only three studies included a follow-up timepoint more than three days after the end of TBS treatment.
“Only three studies included a follow-up timepoint more than three days after the end of TBS treatment (Blumberger et al., 2022;Cole et al., 2020;Cristancho et al., 2023)”
From Neurocognitive effects of theta burst stimulation for treatment-resistant depression in adults: A systematic review and recommendations for future research (2025) · cites this paper as Cristancho et al., 2023
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“sequential bilateral approach of inhibitory stimulation (1 Hz) to the right DLPFC and excitatory stimulation (10 Hz) to the left DLPFC has demonstrated efficacy with standard rTMS(54,55) and theta burst (continuous TBS right and iTBS left)(56) and has recently shown efficacy in older adults.(57,58) Notwithstanding the…”
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- Authors
- Cristancho, P., Arora, J., Nishino, T., Berger, J., Carter, A., Blumberger, D., Miller, P., Snyder, A., Barch, D., & Lenze, E. J.
- Affiliations
- Washington University in St. Louis (US)
- Centre for Addiction and Mental Health (CA)
- Division of Biostatistics School of Medicine Washington University in St. Louis St. Louis Missouri USA
- Corresponding author
- Cristancho, Pilar
- ORCID
- Venue
- International Journal of Geriatric Psychiatry
- Publisher
- Wiley
- Published
- 2022-12-09
- Volume
- 38
- Issue
- 1
- Pages
- e5851-e5851
- ISSN
- 0885-6230 (ISSN-L)
- 1099-1166
- OpenAlex
- W4311672114
- Semantic Scholar
- b08c9142ec735d73544fdb779c991ec88aec8004
- Cited by
- 19
- References
- 59
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 11
- FWCI
- 1.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Journal of Geriatric Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Foundation for Barnes-Jewish Hospital
- National Center for Advancing Translational Sciences (KL2Tr002346)
- Topics
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- geriatric depression, executive dysfunction, cognitive control network, older adults, functional connectivity, frontoparietal network, cingulo-opercular network, working memory, sham-controlled intervention, non-invasive brain stimulation
- MeSH terms
- Aged, Humans, Transcranial Magnetic Stimulation, Executive Function
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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