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Cited by 12Transcranial Magnetic Stimulation StudiesDementia and Cognitive Impairment ResearchTraumatic Brain Injury Research

A phase I trial of accelerated intermittent theta burst rTMS for amnestic MCI

Open access
Aghamoosa, Stephanie, Lopez, James, Rbeiz, Katrina, Fleischmann, Holly H, Horn, Olivia, Madden, Katrina, Caulfield, Kevin A, Antonucci, Michael U +3 more·2024·Journal of Neurology, Neurosurgery & Psychiatry
DOI 10.1136/jnnp-2023-332680PMC PMC11483208
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Abstract

Background: Emerging evidence suggests that repetitive transcranial magnetic stimulation (rTMS) enhances cognition in mild cognitive impairment (MCI). Accelerated intermittent theta burst stimulation (iTBS) rTMS protocols are promising as they substantially reduce burden by shortening the treatment course, but the safety, feasibility, and acceptability of iTBS have not been established in MCI. Methods: 24 older adults with amnestic MCI (aMCI) due to possible Alzheimer’s disease enrolled in a phase I trial of open-label accelerated iTBS to the left dorsolateral prefrontal cortex (8 stimulation sessions of 600 pulses of iTBS/day for 3 days). Participants rated common side effects during and after each session and retrospectively (at post-treatment and 4-week follow-up). They completed brain MRI (for safety assessments and electric field modeling), neuropsychiatric evaluations, and neuropsychological testing before and after treatment; a subset of measures was administered at follow-up. Results: Retention was high (95%) and there were no adverse neuroradiological, neuropsychiatric, or neurocognitive effects of treatment. Participants reported high acceptability, minimal side effects, and low desire to quit despite some rating the treatment as tiring. Electric field modeling data suggest that all participants received safe and therapeutic cortical stimulation intensities. We observed a significant, large effect size (d=0.98) improvement in fluid cognition using the NIH Toolbox Cognition Battery from pre-treatment to post-treatment. Conclusions: Our findings support the safety, feasibility, and acceptability of accelerated iTBS in aMCI. In addition, we provide evidence of target engagement in the form of improved cognition following treatment. These promising results directly inform future trials aimed at optimizing treatment parameters. Trial registration number: NCT04503096.

AI snapshot

Written from the paper’s full text.

TL;DR

In this open-label phase I trial, accelerated intermittent theta burst rTMS to the left dorsolateral prefrontal cortex was safe, feasible, tolerable, and acceptable in older adults with amnestic MCI due to possible Alzheimer’s disease, with 95% retention and no serious adverse events. Fluid cognition improved significantly from pre- to post-treatment (Cohen’s d = 0.98), but the single-arm design precludes efficacy conclusions.

Key findings

  • Safety/feasibility: 24 participants enrolled, 22 initiated treatment, and 21 completed all procedures (95% retention); there were no serious adverse events and no adverse neuroradiological, neuropsychiatric, or neurocognitive effects. MoCA scores showed no decrement pre- to post-treatment (p = .725).
  • Electric field modeling indicated all participants received safe and therapeutic cortical stimulation intensities, with an average E-field magnitude of 65.32 V/m (SD = 10.39; range = 48.53–88.54 V/m).
  • Tolerability/acceptability: modal symptom ratings were 0; headache and pain were the most commonly endorsed symptoms, generally resolving post-session. Participants reported high acceptability and low desire to quit, though some rated treatment as mildly stressful and moderately tiring.
  • Cognition: significant large effect-size improvement in NIH Toolbox Cognition Battery Fluid Cognition Composite from pre- to post-treatment (d = 0.98, p < .001), improving from about −1 SD to −0.7 SD; 17/21 improved, 6/21 improved ≥0.5 SD, and none declined ≥0.5 SD. No significant changes were found on the standard neuropsychological battery, and depressive symptoms did not change (HAM-D p = .296; GDS p = .897).

Methods

  • Open-label phase I single-site trial in older adults with amnestic MCI due to possible AD; 67 screened, 24 enrolled, 22 initiated treatment, 21 completers. Participants were 61.5–85.2 years old (M = 74.1, SD = 5.71), predominantly White/non-Hispanic (n = 23), and roughly half female (n = 13).
  • Intervention: accelerated iTBS to the left dorsolateral prefrontal cortex at F3, delivered as 8 sessions/day for 3 days within an 8-day span, 600 pulses/session, 14,400 total pulses, at 120% resting motor threshold (mean = 43.5 ± 6.2% maximal stimulator output), using MagVenture MagPro with neuronavigation.
  • Measures/analysis: pre- and post-treatment brain MRI, neuropsychiatric scales (C-SSRS, YMRS), MoCA, neuropsychological testing, NIH Toolbox Cognition Battery, HAM-D, and GDS; symptom and acceptability questionnaires during/after sessions and at post-treatment. Paired t-tests, Wilcoxon signed-rank tests for non-normal standard neuropsychology scores, Cohen’s d effect sizes, and R version 4.2.3 were used.

Limitations

  • Stated by the paper: single-arm, open-label design with no sham/comparator, randomization, or blinding; possible placebo/expectancy and practice effects; modest sample size; no formal sample size calculation; durability of gains unknown; syndromic rather than biomarker-based diagnostic characterization.
  • Evident from the text: single-site recruitment and a predominantly White/non-Hispanic, college-educated sample limit generalizability.
  • Evident from the text: the Fluid Cognition Composite was abbreviated because the picture sequence memory test was omitted, and participants engaged in computerized cognitive training (BrainHQ) during inter-session breaks, although sensitivity analyses suggested it did not impact treatment outcomes.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1136/jnnp-2023-332680

Cites

70 of 70 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

26 of 34 cited sources checked · 15 supported · 1 flagged · accuracy not yet measured

  • Premisecitation

    Time commitment is a common barrier to engaging in interventions for older adults with MCI.

    “time commitment is a common barrier to engaging in interventions [53]”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [53] Locke, 2014, A patient-centered analysis of enrollment and retention in a randomized behavioral trial of two cognitive rehabilitation interventions for mild cognitive impairment, J Prev Alzheimers Dis source

      The Discussion says time commitment was a relatively low concern for this group, although it concerned some participants. It identifies travel distance and lack of a program partner as more prominent barriers, contrary to describing time commitment as a common barrier in this study. (LLM, conf=0.86)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
  • Premisecitation

    One randomized, double-blind, sham-controlled iTBS trial in mild to moderate AD dementia found improved associative memory and global cognition after 14 days of 3 stimulation sessions each at 70% rMT (25,200 total pulses).

    “one randomized, double-blind, sham-controlled iTBS trial conducted in mild to moderate AD dementia found improved associative memory and global cognition after 14 days of 3 stimulation sessions each at 70% rMT (25,200 total pulses) [27].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [27] Wu, 2022, Accelerated intermittent Theta-burst stimulation broadly ameliorates symptoms and cognition in Alzheimer’s disease: a randomized controlled trial, Brain Stimul source

      The Methods describe a randomized, double-blind, sham-controlled 14-day iTBS trial in patients with AD, and the Results report improved associative memory and global-cognition scores at week 2. The participant criteria (Methods, §2.3) are consistent with mild to moderate dementia. The passages retrieved from the intervention section do not establish three sessions per day, 70% rMT, or 25,200 total pulses, so those protocol details remain unsupported by the available passages. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
  • Findingcitation

    This improvement is greater than the small-to-medium practice effect reported in the normative sample for this battery.

    “this improvement is greater than the small-to-medium practice effect reported in the normative sample for this battery [44]”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [44] source

      The Results section (Test–Retest Reliability and Practice Effects; page not provided) reports a small-to-medium practice effect for the Fluid Cognition composite (d = 0.42). But that estimate came from 89 retested participants described as a convenience sample, not a normative sample; the Discussion says national norming was still under way. The cited paper also cannot establish whether the citing study’s improvement was greater without that improvement’s magnitude. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
  • Premisecitation

    Individuals with aMCI typically demonstrate attenuated practice effects.

    “individuals with aMCI typically demonstrate attenuated practice effects [54,55]”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [54] Hammers, 2021, Reliable change in cognition over 1 week in community-dwelling older adults: a validation and extension study, Arch Clin Neuropsychol source
    • cites [55] Jutten, 2020, Lower practice effects as a marker of cognitive performance and dementia risk: a literature review, Alzheimers Dement (Amst) source
  • Interpretationown data

    The study provides evidence of target engagement in the form of improved cognition following treatment.

    “we provide evidence of target engagement in the form of improved cognition following treatment.”
    • Also stated in: § DISCUSSION · boosted
      “demonstrating target engagement within less than a third of the treatment days required in the prior study of iTBS for AD [27].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [27] Wu, 2022, Accelerated intermittent Theta-burst stimulation broadly ameliorates symptoms and cognition in Alzheimer’s disease: a randomized controlled trial, Brain Stimul source
  • May combine two claims. 22
  • Classified as probably not a substantial claim. 17

  • May combine two claims.

    Premisecitation

    There is some indication of increased adherence and faster treatment response for accelerated iTBS compared to conventional rTMS.

    “with some indication of increased adherence and faster treatment response compared to conventional rTMS [22–25].”
    Quote in the paperSubstantial claim3 of 4 sources checked
    • cites [22] Tovar-Perdomo, 2017, High frequency repetitive transcranial magnetic stimulation treatment for major depression: dissociated effects on psychopathology and neurocognition, J Affect Disord source

      The rTMS Procedure passage (page unavailable) describes twice-daily high-frequency rTMS, and Psychopathology pre-post HF-rTMS reports symptom improvement by week 3. Neither passage compares accelerated iTBS with conventional rTMS or reports comparative adherence or response speed. Searches for iTBS, adherence, and faster comparative response found no passage addressing that claim. (LLM, conf=0.77)

      Experimental — accuracy not yet measured
    • cites [23] source

      The Results (page unavailable) report a significant treatment effect by Day 3, consistent with an indication of faster response than a conventional multiweek rTMS course. But the Procedures describe accelerated 10 Hz rTMS, not accelerated iTBS, and the Results report two treatment discontinuations without showing increased adherence relative to conventional rTMS. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [24] source
    • cites [25] Williams, 2018, High-dose spaced Theta-burst TMS as a rapid-acting antidepressant in highly refractory depression, Brain source

      The Letter to the Editor (page unavailable) reports that accelerated iTBS produced responses in five of six participants by the end of a five-day course, supporting an indication of rapid response. It does not establish a faster response than conventional rTMS or increased adherence; one participant stopped treatment early. The study was small, open-label, and had no conventional-rTMS comparison group. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    The l-dlPFC is a key node of the frontoparietal network that is less activated during cognitive tasks in MCI relative to healthy controls.

    “the l-dlPFC (i.e., middle frontal gyrus) being a key node of the frontoparietal network that is less activated during cognitive tasks in MCI relative to healthy controls [16].”
    Quote in the paperSubstantial claim1 of 1 sources checked

  • May combine two claims.

    Interpretationcitation

    The observed E-field values are considered to be in the therapeutic range and consistent with expectations given 120% rMT stimulation.

    “These values are considered to be in the therapeutic range and consistent with expectations given 120% rMT stimulation [52].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [52] Van Hoornweder S , Nuyts M , Frieske J , et al . A systematic review and large-scale Tes and TMS electric field modeling study reveals how outcome measure selection alters results in a person- and montage-specific manner. bioRxiv 2023.:2023.02.22.529540. doi:10.1101/2023.02.22.529540 source

      The Electric Field Models section (p. 5) reports simulations at 50% stimulator output, not 120% resting motor threshold. Recommendation #3 (pp. 28–29) discusses why an optimal E-field dose depends on the outcome measure and other factors, but does not identify a therapeutic range or establish that the citing paper’s values fall within one. Searches for 120% rMT and a therapeutic E-field range found no passage addressing either assertion. (LLM, conf=0.76)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Study design and conductreasoning

    A formal sample size calculation was not performed; sample size was based on the primary aims of generating estimates of feasibility, acceptability, and outcome variability for future trials.

    “Since this was a phase I feasibility study, a formal sample size calculation was not performed but was instead based on our primary aims of generating estimates of feasibility, acceptability, and outcome variability to aid in the planning of future sufficiently powered trials [49].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [49] Eldridge, 2016, CONSORT 2010 statement: extension to randomised pilot and feasibility trials, BMJ source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The optimal inter-session interval for same-day rTMS sessions has not been systematically evaluated.

    “the optimal inter-session interval for same-day rTMS sessions has not been systematically evaluated, with protocols ranging from 10 minutes to 2 hours [19]”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [19] Caulfield, 2022, A Transdiagnostic review of safety, efficacy, and parameter space in accelerated transcranial magnetic stimulation, J Psychiatr Res source

      In Results, Part 3 (page unavailable), the review says the effect of intersession interval on treatment response is unclear and cannot be disentangled from other parameters in published datasets. But Discussion, Area 3 (page unavailable), describes a study that systematically compared 0-, 10-, and 30-minute intervals using MEP changes, so saying the interval has not been systematically evaluated is too absolute. The cited 10-minute-to-2-hour range is also not the review’s reported range: it describes intervals up to 640 minutes across diagnoses. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    The NIH Toolbox Cognition Battery was developed using advanced psychometrics to attenuate floor or ceiling effects, making it ideal for assessing change.

    “which was developed using advanced psychometrics to attenuate floor or ceiling effects [43], thereby making it ideal for assessing change.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [43] source

      The Development of the Cognition Battery section describes computer-adaptive testing and item response theory for the language tests, but not for the entire battery. The Results summary reports minimal floor and ceiling effects in adults aged 20–65 and calls the findings encouraging for repeated and longitudinal measurement. It does not establish that advanced psychometrics attenuated those effects or that the battery is ideal for assessing change. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Study design and conductcitation

    The picture sequence memory test was not administered to mitigate participant burden and to minimize practice effects.

    “The picture sequence memory test was not administered to mitigate participant burden and to minimize practice effects given that it has been reported to have the largest effect size change over a comparable retest interval [43].”
    Quote in the paperSubstantial claim1 of 1 sources checked

  • May combine two claims.

    Interpretationcitation

    That no adverse events occurred is noteworthy because older adults have a higher likelihood of brain lesions, which may increase risk for TMS-related adverse events.

    “Older adults have a higher likelihood of having brain lesions [50] which may increase risk for TMS-related adverse events [51]; that no adverse events (e.g. seizures) occurred is therefore noteworthy.”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [50] Sandeman, 2013, Incidental findings on brain MR imaging in older community-dwelling subjects are common but serious medical consequences are rare: a cohort study, PLoS One source
    • cites [51] source

  • May combine two claims.

    Premisecitation

    The l-dlPFC is integral to higher-order cognition and modulates episodic memory in MCI by enhancing encoding and facilitating retrieval.

    “l-dlPFC is integral to higher-order cognition (i.e., executive function) [10,11], which modulates episodic memory in MCI by way of enhancing encoding and facilitating retrieval [12–14].”
    Quote in the paperSubstantial claim3 of 5 sources checked
    • cites [10] source
    • cites [11] source
    • cites [12] source

      The passage labeled Abstract (page unavailable) says that declining executive function impairs strategic processing at encoding and retrieval, supporting a general link between executive function and memory. It discusses age-associated frontal-striatal changes, but does not establish this mechanism specifically for the left dorsolateral prefrontal cortex or for people with MCI. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [13] source
    • cites [14] source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    A Brainsight Neuronavigation system ensured accuracy, reliability, and reproducibility of coil placement both within and between sessions.

    “A Brainsight Neuronavigation system (Version 2.4.8) ensured accuracy, reliability, and reproducibility of coil placement both within and between sessions [35].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [35] Caulfield, 2022, Neuronavigation maximizes accuracy and precision in TMS positioning: evidence from 11,230 distance, angle, and electric field modeling measurements, Brain Stimul source

      The Results (Experiment 1A–B; page unavailable) report substantially smaller coil-placement deviations with neuronavigation than with cap targeting across sessions, supporting improved accuracy and consistency. The Methods (Neuronavigation procedure; page unavailable) identify the system as Brainsight Version 2.4.7, not the citing sentence’s Version 2.4.8. The paper supports improved placement rather than a guarantee that placement was accurate and reproducible within and between sessions. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    High frequency rTMS to l-dlPFC is well-established efficacious for alleviating depression, particularly in older adults.

    “the well-established efficacy of high frequency rTMS to l-dlPFC for alleviating depression, particularly in older adults [58]”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [58] Valiengo, 2022, Repetitive transcranial magnetic stimulation for major depressive disorder in older adults: systematic review and meta-analysis, J Gerontol A Biol Sci Med Sci source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Roughly half of the sample was female (n = 13).

    “roughly half female (n = 13)”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    At baseline, participants performed about −1 SD below the normative mean on fluid cognition, improving to −0.7 SD at post-treatment.

    “At baseline, participants performed about −1 SD below the normative mean (T = 50, SD = 10) on average and this improved to −0.7 SD at post-treatment.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Participants rated several logistical matters favorably, including the condensed treatment schedule, scheduling flexibility, and interactions with study staff.

    “They also rated several logistical matters favorably, including the condensed treatment schedule, scheduling flexibility, and interactions with study staff.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    The sample was composed of older adults with a mean age of 74.1 years (range 61.5-85.2, SD = 5.71).

    “This sample was composed of older adults (range: 61.5 – 85.2 years, M = 74.1, SD = 5.71)”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Momentary assessments revealed that although some participants experienced moderate levels of expected symptoms (headache, scalp pain) during stimulation, these ratings returned to mild/none after stimulation ceased.

    “Momentary assessments revealed that although some participants experienced moderate levels of expected symptoms (i.e., headache, scalp pain) during stimulation, these ratings returned to mild/none after stimulation ceased.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    All participants were independent per the Lawton instrumental activities of daily living scale, scoring 8/8 except one who scored 6/8.

    “all participants were independent per the Lawton instrumental activities of daily living scale [33]; all scored 8/8 (i.e., no difficulties), except for one participant who scored 6/8 due to choosing not to drive and receiving reminders to take their medications.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [33] Graf, 2008, The Lawton instrumental activities of daily living scale, Am J Nurs source

  • May combine two claims.

    Findingown data

    Participants felt highly motivated, interested, and committed to completing the treatment.

    “feeling highly motivated, interested, and committed to completing the treatment.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    The sample was predominantly White/non-Hispanic (n = 23; Black/non-Hispanic: n = 1).

    “predominantly White/non-Hispanic (n = 23; Black/non-Hispanic: n = 1)”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    Out of 67 potential participants screened, 24 individuals with aMCI were enrolled and 22 initiated treatment.

    “Out of 67 potential participants screened, 24 individuals with aMCI were enrolled; 22 initiated treatment (see Figure 1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingreasoning

    Treatment was rated as highly tolerable and acceptable.

    “treatment was rated as highly tolerable and acceptable”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Most participants reported high motivation, interest, and commitment to the treatment paired with low desire to quit and an openness to engage in future treatment.

    “most participants reporting high motivation, interest, and commitment to the treatment paired with low desire to quit and an openness to engage in future treatment”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    The sample had a college education on average (range 12-20 years, M = 15.9, SD = 2.5).

    “with a college education on average (range: 12 – 20 years, M = 15.9, SD = 2.5).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Across all measures, effects were generally rated as minimal/mild when experienced, and most participants reported none.

    “Across all measures, effects were generally rated as minimal/mild when experienced, and most participants reported none.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    10-15 minutes is safe and highly acceptable as an inter-session interval for same-day rTMS sessions.

    “our findings suggest that 10–15 minutes is safe and highly acceptable”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductnone given

    Each MRI study was reviewed by a board-certified neuroradiologist to identify any pre- to post-treatment change and to document incidental findings.

    “Each study was reviewed by a board-certified neuroradiologist (M.A.) to identify any pre- to post-treatment change and to document incidental findings (see Supplement for acquisition parameters).”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    The study used the NIHTB-CB.

    “our use of the NIHTB-CB”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    The final sample size of N = 21 treatment completers will allow estimates of standard deviations of continuous outcome variables for future sample size calculations.

    “Our final sample size of N = 21 treatment completers will allow us to obtain estimates of the standard deviations of continuous outcome variables with which to conduct sample size calculations for a future definitive trial.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    The study took a comprehensive approach to monitoring side effects, incorporating current and retrospective ratings at multiple timescales.

    “We took a comprehensive approach to monitoring side effects, incorporating both current and retrospective ratings at a range of timescales (i.e., in the moment, in the previous 24–48 hours, and over the duration of the treatment).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    iTBS has shown promise in enhancing cognition in healthy adults.

    “iTBS has shown promise in enhancing cognition in healthy adults [26]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [26] Pabst, 2022, A systematic review and meta-analysis of the efficacy of intermittent Theta burst stimulation (iTBS) on cognitive enhancement, Neurosci Biobehav Rev source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    The trial was registered on ClinicalTrials.gov and approved by the Medical University of South Carolina Institutional Review Board.

    “This open-label phase I trial was registered on ClinicalTrials.gov (NCT04503096) and approved by the Medical University of South Carolina Institutional Review Board (Pro00100536).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Accelerated iTBS may be a more feasible and accessible treatment option for people with MCI than conventional rTMS.

    “Thus, accelerated iTBS may be a more feasible and accessible treatment option for people with MCI than conventional rTMS.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Completing a conventional course of rTMS, requiring 4–6 weeks of once daily treatment, is burdensome and logistically difficult for those with cognitive impairment.
    • Rests on an assumption: There is a lack of studies of accelerated iTBS for MCI.

  • May combine two claims.

    Study design and conductreasoning

    The findings are limited by the single-arm, open-label design of this phase I trial; there was no sham or comparator condition, randomization, or blinding of participants or experimenters.

    “our findings are limited by the single-arm, open-label design of this phase I trial; there was no sham or comparator condition, randomization, or blinding of participants or experimenters.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    It remains possible that the improvements in fluid cognition may be attributable, at least in part, to placebo effect.

    “it remains possible that the improvements in fluid cognition may be attributable, at least in part, to placebo effect”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The study provided transparent reporting of all dosing parameters to facilitate replication or systematic investigations of individual parameters in future studies.

    “We have provided transparent reporting of all dosing parameters to facilitate replication or systematic investigations of individual parameters in future studies.”
    Quote in the paperNot a substantial claim
35 of 35

  • The paper relies on this without support.

    Completing a conventional course of rTMS, requiring 4–6 weeks of once daily treatment, is burdensome and logistically difficult for those with cognitive impairment.

    “While these emerging findings are promising, completing a conventional course of rTMS, requiring 4–6 weeks of once daily treatment, may be burdensome and logistically difficult for those with cognitive impairment.”

  • The paper relies on this without support.

    There is a lack of studies of accelerated iTBS for MCI.

    “With the lack of studies of accelerated iTBS for MCI, an important first step towards advancing this promising, low-burden neuromodulation treatment is to systematically evaluate its safety and to carefully consider factors that may impact its implementation.”

  • The paper relies on this without support.

    Accelerated iTBS substantially reduces the frequency and duration of treatment sessions.

    “One of the greatest benefits of accelerated iTBS is the substantial reduction in the frequency and duration of treatment sessions.”

  • The paper relies on this without support.

    The NIHTB-CB is more psychometrically robust than standard neuropsychological tests.

    “which is more psychometrically robust than standard neuropsychological tests”
4 of 4

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. American Psychiatric Association . Diagnostic and statistical manual of mental disorders (DSM-5®). American Psychiatric Pub, 2013. Available: https://psychiatryonline.org/doi/book/10.1176/appi.books.9780890425596 · DOI · Paper page

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Authors
Aghamoosa, S., Lopez, J., Rbeiz, K., Fleischmann, H. H., Horn, O., Madden, K., Caulfield, K. A., Antonucci, M. U., Revuelta, G., McTeague, L. M., & Benitez, A.
Affiliations
Medical University of South Carolina (US)
Corresponding author
Aghamoosa, Stephanie
ORCID
Venue
Journal of Neurology, Neurosurgery & Psychiatry
Publisher
BMJ
Published
2024-05-06
Volume
95
Issue
11
Pages
1036-1045
ISSN
  • 0022-3050 (ISSN-L)
  • 1468-330X
DOI
10.1136/jnnp-2023-332680
PMC
PMC11483208
OpenAlex
W4396673621
Semantic Scholar
5a0c478ac60cb6a879a94b7abc28cf810fd9ac00
Cited by
12
References
70
Citations by year
2026: 5 · 2025: 4 · 2024: 3
FWCI
1.87
Type
journal article
Language
en
Open access
Locations
  • Journal of Neurology Neurosurgery & Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion)
Funders
  • National Center for Medical Rehabilitation Research (P2CHD086844 pilot project #29)
  • Alzheimer's Association (AARF-21-850073)
  • National Institute of General Medical Sciences (P20 GM109040)
  • New Vision Research Foundation (NVR2020-001-3)
  • National Institute on Aging (1R01AG081237-01)
Topics
  • Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
Keywords
accelerated intermittent theta burst stimulation, repetitive transcranial magnetic stimulation, amnestic mild cognitive impairment, Alzheimer's disease, dorsolateral prefrontal cortex, fluid cognition, treatment safety and feasibility, treatment acceptability, electric field modeling, target engagement, older adults
MeSH terms
Dorsolateral Prefrontal Cortex, Aged, Aged, 80 and over, Alzheimer Disease, Amnesia, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neuropsychological Tests, Theta Rhythm, Treatment Outcome, Transcranial Magnetic Stimulation, Cognitive Dysfunction

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.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-28.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-28.

Cited sources are checked by gpt-6-sol.

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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