Different forms of prefrontal theta burst stimulation for executive function of medication-resistant depression: Evidence from a randomized sham-controlled study
Abstract
Background Even during symptomatic remission, many patients with medication resistant depression (MRD) still demonstrate impaired cognitive function, especially executive function (EF). Theta-burst transcranial magnetic stimulation (TBS) modulates cortical excitability and may treat MRD. Evidences from previous studies show that intermittent TBS (iTBS) produces cortical excitatory effects, while continuous TBS (cTBS) produces a reduction of cortical excitability. EF is highly dependent on prefrontal activity, but the effects of different forms of prefrontal TBS on EF remain unknown. Methods 60 MRD patients were recruited and randomly assigned to one of four groups. Treatment was determined by the group to which an individual was assigned; A: cTBS 1800pulses/session; B: iTBS 1800pulses/session; C: a combination of cTBS+iTBS, 1800pulses/session for each; and D: sham TBS. Wisconsin Card Sorting Test (WCST) for the performance of EF was evaluated before and after 10 daily treatment sessions Results Repeated measures ANOVA, with each WCST index at baseline and 2weeks after TBS as within-subject factors, demonstrated that a statistically significant interaction of TBS groups (G) and antidepressant responses [(R), responses were defined as >50% reduction of depression scores after 2-weeks TBS treatment] on the before-versus-after changes of all WCST indexes (G×R, p<0.05). Responders in Group B, but not in the other groups, showed a significant improvement in WCST performance. Only nonresponders in Group A showed a trend for EF worsening. Conclusions Our findings showed that left prefrontal iTBS, not right prefrontal cTBS, improved EF, and this can be independent from its antidepressant effects.
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The study conducted by Cheng et al. demonstrated that left prefrontal iTBS, not right prefrontal cTBS, exhibited a positive effect on executive function, which may be unrelated to its antidepressant properties.
“Moreover, the study conducted by Cheng et al22 demonstrated that left prefrontal iTBS, not right prefrontal cTBS, exhibited a positive effect on executive function, which may be unrelated to its antidepressant properties.”
From Can Intermittent Theta-Burst Stimulation of Dorsolateral Prefrontal Cortex Relieve Executive Dysfunction in Patients With Late-Life Depression? (2024) · cites this paper as [22]
There were findings of neurocognitive enhancement in executive function (Cheng et al., 2016; Cristancho et al., 2020; Scho et al., 2019).
“executive function (Cheng et al., 2016;Cristancho et al., 2020;Scho et al., 2019)”
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 Cheng et al., 2016
Executive function was the most common neurocognitive domain examined in the included studies.
“Executive function was the most common neurocognitive domain examined in the included studies (Blumberger et al., 2022;Cheng et al., 2016;Cole et al., 2020;Cole et al., 2022;Cristancho et al., 2020;Cristancho et al., 2023;Scho et al., 2019)”
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 Cheng et al., 2016
Cheng et al. (2016) found that changes in complex problem solving and concept formation on the Wisconsin Card Sorting Test were dependent on the type of TBS used and if it had antidepressant benefit.
“Cheng et al. (2016) used the Wisconsin Card Sorting Test (WCST) and found that changes in complex problem solving and concept formation were dependent on the type of TBS used and if it had antidepressant benefit.”
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 Cheng et al., 2016
No other groups (cTBS, iTBS and cTBS, sham TBS) experienced significant change in performance from baseline to post-treatment on the WCST regardless of response, despite large reductions in depression severity between baseline and post-treatment for responders in the active groups (cTBS: -22.5%; iTBS and cTBS: -52.5%).
“In addition, no other groups (cTBS, iTBS and cTBS, sham TBS) experienced significant change in performance from baseline to post-treatment on the WCST regardless of response, despite large reductions in depression severity between baseline and post-treatment for responders in the active groups (cTBS: -22.5 %; iTBS and cTBS: -52.5 %).”
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 Cheng et al., 2016
In five included studies, participants received bilateral TBS.
“In five studies (Blumberger et al., 2022;Cheng et al., 2016;Cristancho et al., 2020;Cristancho et al., 2023;Holczer et al., 2021), participants received bilateral TBS.”
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 Cheng et al., 2016
Some evidence suggested that TBS, independent of its improvement in depression severity, may be associated with improvement in attention, processing speed, aspects of executive function, and verbal recognition.
“and some evidence suggested that TBS, independent of its improvement in depression severity (Cheng et al., 2016;Fitzgerald et al., 2020), may be associated with improvement in attention, processing speed, aspects of executive function, and verbal recognition.”
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 Cheng et al., 2016
Participants who received iTBS alone and experienced a 50% reduction in depression severity (responders) relative to those who had no response showed substantial improvements in WCST performance, including more total correct and conceptual level responses, and fewer errors.
“Participants who received iTBS alone and experienced a 50 % reduction in depression severity (responders) relative to those who had no response showed substantial improvements in WCST performance, including more total correct and conceptual level responses, and fewer errors.”
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 Cheng et al., 2016
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- Authors
- Cheng, C.-M., Juan, C.-H., Chen, M.-H., Chang, C.-F., Lu, H. J., Su, T.-P., Lee, Y.-C., & Li, C.-T.
- Affiliations
- Taipei Veterans General Hospital (TW)
- National Central University (TW)
- Corresponding author
- Li, Cheng-Ta
- Venue
- Progress in Neuro-Psychopharmacology and Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2016-04
- Volume
- 66
- Pages
- 35-40
- ISSN
- 0278-5846 (ISSN-L)
- OpenAlex
- W2271204888
- Cited by
- 63
- References
- 38
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 5 · 2023: 12 · 2022: 7 · 2021: 9 · 2020: 4 · 2019: 4 · 2018: 4 · 2017: 4 · 2016: 2
- FWCI
- 1.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Progress in Neuro-Psychopharmacology and Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Taipei Veterans General Hospital (VGHHUST101-G4-1-2, VGHHUST102-G4-3-1, V103B-007, V103E9-005, V104E9-003, V104B-002)
- Ministry of Science and Technology (103-2314-B-075-072-MY, 104-2325-B-039-004)
- Military Medical Bureau (DV103-12)
- Topics
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
- Keywords
- treatment-resistant depression, theta-burst transcranial magnetic stimulation, intermittent theta burst stimulation, continuous theta burst stimulation, executive function, prefrontal cortex, cortical excitability, cognitive impairment in depression, Wisconsin Card Sorting Test, antidepressant response, treatment response
- MeSH terms
- Adult, Aged, Cognition, Female, Humans, Male, Middle Aged, Neuropsychological Tests, Treatment Outcome, Prefrontal Cortex, Transcranial Magnetic Stimulation, Young Adult, Executive Function, Depressive Disorder, Treatment-Resistant
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