Frontal Pole Neuromodulation for Impulsivity and Suicidality in Veterans With Mild Traumatic Brain Injury and Common Co-Occurring Mental Health Conditions: Protocol for a Pilot Randomized Controlled Trial

May combine two claims.

Individuals without a history of mTBI who attempted suicide or have a history of SI also show diminished VMPFC volume and reduced connectivity between the prefrontal cortex and the limbic system.

“Interestingly, individuals without a history of mTBI who attempted suicide or have a history of SI also show diminished VMPFC volume and reduced connectivity between the prefrontal cortex and the limbic system, further supporting it as a potential therapeutic target [31,81].”

• cites [31] sourceDisputed

  The Methods define the ventromedial prefrontal cortex as part of the MPFC region studied. The Discussion reports structural impairments in suicide attempters in the VLPFC, DPFC and OFC, but not MPFC—contrary to the claimed VMPFC reduction. This structural imaging study does not establish reduced prefrontal–limbic connectivity or the claim about people with suicidal ideation or no mTBI history. (LLM, conf=0.88)

  Checked by a reasoning model — may be wrong.

  Experimental — accuracy not yet measured
• cites [81] sourcePartly supported

  The Results report reduced frontal-lobe volume in psychiatric inpatients who recently attempted suicide compared with depressed non-attempters. They do not identify a VMPFC reduction, and they found no significant volumetric differences for the suicidal-ideation group. The study assessed brain volumes, not prefrontal–limbic connectivity; its Methods establish absence of head trauma for healthy controls, not for the psychiatric patients. (LLM, conf=0.89)

  Experimental — accuracy not yet measured

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

TMS was approved by the US Food and Drug Administration in 2008 for the treatment of major depressive disorder.

“TMS was subsequently approved by the US Food and Drug Administration (FDA) in 2008 for the treatment of major depressive disorder [20].”

• cites [20] sourcePartly supported

  The Abstract states that the NeuroStar TMS device received FDA approval in October 2008 for a specific form of medication-refractory depression. The Discussion clarifies that approval was limited to a specified protocol, device, and patient population. The citing sentence gets the year and depression indication right but describes the approval more broadly than the source does. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

May combine two claims.

A meta-analysis of psychosocial factors found that difficulties in social and occupational functioning were strongly tied to increased levels of SI, social isolation, and low socioeconomic status and are directly associated with increased incidences of SI and completed suicides.

“A meta-analysis of psychosocial factors found that difficulties in social and occupational functioning were strongly tied to increased levels of SI, social isolation, and low socioeconomic status and are directly associated with increased incidences of SI and completed suicides (Figure 1) [48].”

• cites [48] sourcePartly supported

  The Social integration section links weaker social connections to higher suicide mortality, and the Socioeconomic status section links lower socioeconomic position to suicidal ideation and suicide deaths. But the paper describes itself as a narrative overview, not a meta-analysis, and it does not establish that difficulties in social and occupational functioning directly cause increased suicidal ideation or suicide. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

In iTBS, 50 Hz triplets are applied at a theta rhythm of 5 Hz, which is thought to facilitate long-term potentiation in less time and with fewer pulses than standard TMS, which generally is administered at 5 to 10 Hz.

“In iTBS, 50 Hz triplets are applied at a theta rhythm (5 Hz), which is thought to facilitate long-term potentiation in less time and with fewer pulses than standard TMS, which generally is administered at 5 to 10 Hz [57].”

• cites [57] sourcePartly supported

  The Introduction (page unavailable) describes theta bursts repeated at 5 Hz for LTP induction, and ‘Economy’ of Theta-Burst Stimulation (page unavailable) reports that theta bursts induced LTP with fewer pulses than unpatterned stimulation. The experiments described used four-pulse bursts at 100 Hz in hippocampal tissue; these passages do not establish the 50 Hz triplets of iTBS, a shorter administration time, or a comparison with standard TMS administered at 5–10 Hz. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

Studies demonstrate that this number of pulses results in an optimal window of cortical excitability, and additional pulses may have an inhibitory effect.

“Studies demonstrate that this number of pulses results in an optimal “window” of cortical excitability, and additional pulses may have an inhibitory effect [59-61].”

• cites [59] sourceNot checked — no full text of the source
• cites [60] sourcePartly supported

  The Results (iTBS versus ProiTBS; page unavailable) report that conventional intermittent theta-burst stimulation increased motor-cortex excitability, while prolonged stimulation suppressed it. The Introduction says pulse number and other parameters still need evaluation to optimize stimulation, so the study does not establish that the cited pulse count is an optimal window. (LLM, conf=0.84)

  Experimental — accuracy not yet measured
• cites [61] sourcePartly supported

  The section on iTBS aftereffects reports that earlier studies observed decreases in cortical excitability after repeated stimulation, supporting the possibility of an inhibitory effect. But this study found no such decrease: a third block, bringing the total to 1800 pulses, further increased excitability. Its Conclusions therefore do not establish the claimed optimal pulse window. (LLM, conf=0.83)

  Experimental — accuracy not yet measured

May combine two claims.

In a national US VA TMS study of 770 veterans receiving TMS, nearly half had mTBI, and TMS was demonstrated to be equally safe in veterans with and without mTBI.

“Specifically, in a national US VA TMS study of 770 veterans receiving TMS, nearly half had mTBI, and TMS was demonstrated to be equally safe in veterans with and without mTBI [64].”

• cites [64] sourcePartly supported

  The Abstract (Results) reports 770 veterans receiving at least one TMS session, and Results (Safety) reports significant adverse outcomes in fewer than 1% of patients overall. Our copy does not report that nearly half had mTBI or compare safety between veterans with and without mTBI; searches for mTBI and traumatic brain injury did not find such an analysis. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

May combine two claims.

TMS has demonstrated efficacy in the treatment of PTSD, chronic pain, cognitive deficits, and headaches in individuals with mTBI.

“TMS also has demonstrated efficacy in the treatment of posttraumatic stress disorder (PTSD), chronic pain, cognitive deficits, and headaches in individuals with mTBI [23-27].”

• cites [23] sourcePartly supported

  The Results section on PTSD symptoms following concussion reports a statistically significant finding in a small veteran subgroup, but says the evidence consists of small pilot trials. The Results section on cognitive symptoms reports no significant benefit on cognitive assessments, including in a sham-controlled trial. The Discussion mentions chronic pain and headache as co-occurring symptoms, not as conditions for which this paper demonstrates TMS efficacy. Page numbers are unavailable in our copy. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites [24] sourcePartly supported

  The Introduction reports that TMS has improved cognitive functions and psychological problems including PTSD in people with TBI. It does not limit those findings to mild TBI, and the paper’s analysis concerns cognition rather than chronic pain or headaches. Although the References list a study of TMS for mild-TBI-related headaches, that citation alone does not establish demonstrated efficacy for headaches. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites [25] sourceNot checked — no full text of the source
• cites [26] sourceNot checked — no full text of the source
• cites [27] sourcePartly supported

  The ‘rTMS as a PTSD treatment’ section reports studies with improved PTSD symptoms, and the TBI-treatment section describes preliminary evidence of symptom improvement in 15 people with mTBI (page numbers unavailable). It does not establish efficacy for chronic pain, cognitive deficits, or headaches in people with mTBI; it also cautions that TBI treatment evidence is limited. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

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

An overall estimate of 70% of individuals with mTBI struggle with at least one psychiatric comorbidity.

“An overall estimate of 70% of individuals with mTBI struggle with at least one psychiatric comorbidity [65].”

• cites [65] sourcePartly supported

  The POST-TBI PSYCHIATRIC DISORDERS section (page unavailable) reports that 74.5% received a psychiatric diagnosis over five years, but that sample consisted predominantly of people with moderate to severe TBI, not mTBI. It also reports a 34.0% first-year rate for mild TBI in a medical-file review, so the approximately 70% figure is not supported as an overall estimate for mTBI. (LLM, conf=0.90)

  Experimental — accuracy not yet measured

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

The Patient Health Questionnaire-9 has Cronbach alpha=0.9 (very high).

“Cronbach α=0.9 (very high) [110]”

• cites [110] sourceSupported

May combine two claims.

Studies on TMS for suicidality are often limited by small sample sizes, inconsistencies in how suicidality is measured across studies, and contradictory findings.

“Studies are often limited by small sample sizes, inconsistencies in how suicidality is measured across studies, and contradictory findings [75,76].”

• cites [75] sourcePartly supported

  The Discussion (page not provided) identifies the small sample size as this study’s main limitation, and the Secondary Outcomes section reports a suicide-symptom result measured with the BSSI. The paper does not establish that TMS studies of suicidality often use inconsistent measures or have contradictory findings across studies; its small-sample limitation concerns this particular trial. (LLM, conf=0.85)

  Experimental — accuracy not yet measured
• cites [76] sourcePartly supported

  The “Studies of TMS in Depressed Adolescents” section (page unavailable) describes only 112 participants across 10 publications, mostly case reports and open-label studies, supporting the small-sample limitation. The Safety section identifies suicidality as a concern but does not describe inconsistent measures of suicidality or contradictory findings across studies. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

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

The Clinically Administered PTSD Scale for DSM-5 has interrater reliability K=0.78-1.0 (high) and discriminant validity rs=0.02-0.54 (moderate).

“Interrater reliability K=0.78-1.0 (high) discriminant validity: rs=0.02−0.54 (moderate) [100]”

• cites [100] sourcePartly supported

  The Results sections on interrater reliability and convergent and discriminant validity report the stated CAPS-5 ranges: κ = .78 to 1.0 and rs = .02 to .54. However, the paper calls correlations of .33 to .54 moderate and those of .02 and .18 weak, so describing the entire discriminant-validity range as moderate overstates the finding. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

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

The Difficulties in Emotion Regulation Scale has Cronbach alpha=0.90 (very high).

“Cronbach α=0.90 (very high) [120]”

• cites [120] sourceCould not verify

  The cited correction says only that a funding note was missing from the original article (p. 1, correction notice and Funding). A search of our copy for Cronbach’s alpha and 0.90 found no reliability estimate, so this correction does not verify the claimed value. (LLM, conf=0.76)

  Experimental — accuracy not yet measured

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

The authors used the CONSORT checklist when writing their report.

“We used the CONSORT (Consolidated Standards of Reporting Trials) checklist when writing our report [86].”

• cites [86] sourceSupported

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

The Delayed Discounting Task has test-retest reliability rtt=0.89 (very high).

“Test-retest reliability rtt=0.89 (very high) [122]”

• cites [122] sourceSupported

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

The Drug Use Disorders Identification Test has Cronbach alpha=0.93 (very high) and convergent validity r=0.76 (high).

“Cronbach α=0.93 (very high), convergent validity r=0.76 (high) [102,103]”

• cites [102] sourceNot checked — no full text of the source
• cites [103] sourceSupported

May combine two claims.

Studies show that both TMS and iTBS appear safe and effective when administered to other anatomical sites in individuals with mTBI.

“as studies show that both TMS and iTBS appear safe and effective when administered to other anatomical sites in individuals with mTBI [23-26].”

• cites [23] sourcePartly supported

  The Abstract Results (page unavailable) support the safety of rTMS after concussion but say evidence for efficacy is limited. The Results section on PTSD (page unavailable) reports a statistically significant finding in a small concussion subgroup of a theta-burst trial, while the Discussion says all reviewed studies targeted the DLPFC. The paper therefore does not establish that both approaches are effective across other anatomical sites in people with mTBI. (LLM, conf=0.87)

  Experimental — accuracy not yet measured
• cites [24] sourcePartly supported

  The Introduction (page not available) reports improvements after TMS stimulation of several brain regions in people with TBI. But the paper does not establish that both TMS and iTBS are safe and effective specifically in people with mild TBI; it discusses TBI more broadly and does not identify iTBS as a separately evaluated intervention. (LLM, conf=0.84)

  Experimental — accuracy not yet measured
• cites [25] sourceNot checked — no full text of the source
• cites [26] sourceNot checked — no full text of the source

May combine two claims.

iTBS can be applied to the frontal pole to target the VMPFC, and iTBS to the frontal pole is tolerable, with no more subjective pain than TMS.

“iTBS can be applied to the frontal pole to target the VMPFC, and iTBS to the frontal pole is tolerable, with no more subjective pain than TMS [63].”

• cites [63] sourcePartly supported

  The Methods report continuous theta-burst stimulation at the frontal pole (FP1), but intermittent theta-burst stimulation (iTBS) at F3, not the frontal pole. The Results and Conclusions find that ramped frontal-pole TMS was tolerable and not significantly more painful than DLPFC TMS; they do not establish this specifically for frontal-pole iTBS. The Introduction identifies the frontal pole as part of the medial prefrontal cortex but does not identify the stimulated site as the VMPFC. (LLM, conf=0.90)

  Experimental — accuracy not yet measured

May combine two claims.

Frontal pole iTBS allows for more direct stimulation of the VMPFC and modulation of the limbic system.

“This approach allows for more direct stimulation of the VMPFC and modulation of the limbic system [63,82].”

• cites [63] sourcePartly supported

  The Introduction (page unavailable) identifies the frontal pole as part of the medial prefrontal cortex and discusses TMS modulation of frontal-pole activity. But the Methods (page unavailable) specify continuous theta-burst stimulation at the frontal pole and iTBS at F3, not the frontal pole. The paper does not establish more direct VMPFC stimulation or limbic-system modulation by frontal-pole iTBS. (LLM, conf=0.83)

  Experimental — accuracy not yet measured
• cites [82] sourcePartly supported

  The Discussion (§§4.1 and 4.3; page unavailable) supports targeting the frontal pole more directly than the DLPFC and reports changes in connected salience- and reward-related regions. But the study tested continuous theta-burst stimulation (cTBS), not iTBS, and does not establish direct stimulation of the VMPFC specifically. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

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

The Structured Clinical Interview for DSM-5, Research Version has K>0.4 (above average) and sensitivity of identifying diagnosis >0.8 (good).

“K>0.4 (above average) sensitivity of identifying diagnosis >0.8 (good) [105]”

• cites [105] sourcePartly supported

  The Results report sensitivity above 0.80 for all diagnoses and kappa above 0.4 for all diagnoses except anxiety disorders, for which kappa was 0.34. The study evaluated the SCID-5 Clinician Version, not the Research Version named in the claim. (LLM, conf=0.90)

  Experimental — accuracy not yet measured

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

The UPPS-P Negative Urgency subscale has Cronbach alpha=0.91 (very high).

“Cronbach α=0.91 (very high) [41,97]”

• cites [41] sourceCould not verify

  The Method > Measures section describes the four-trait UPPS scale and gives a mean and standard deviation for Negative Urgency, but no Cronbach alpha. Searches for “0.91,” “Cronbach alpha,” and Negative Urgency reliability found no passage supporting the claimed value; the copy also identifies the instrument used as UPPS, not UPPS-P. Page numbers were unavailable. (LLM, conf=0.75)

  Experimental — accuracy not yet measured
• cites [97] sourceNot checked — no full text of the source

May combine two claims.

The right frontal pole anatomical location is easily identifiable using anatomical landmarks and correlates with electrode FP2 on a 10-20 EEG, a region overlapping with the right VMPFC.

“The anatomical location is easily identifiable using anatomical landmarks and correlates with electrode frontal polar cortex (FP; FP2) on a 10 to 20 electroencephalogram, a region overlapping with the right VMPFC [22,63,82].”

• cites [22] sourceCould not verify

  The Materials and Methods section describes TMS delivered primarily to the left dorsolateral prefrontal cortex, but does not describe how to locate the right frontal pole. Searches for FP2, VMPFC, and anatomical landmarks found no passage establishing the claimed EEG correspondence or overlap. (LLM, conf=0.76)

  Experimental — accuracy not yet measured
• cites [63] sourcePartly supported

  The Introduction identifies the frontal pole as part of the medial prefrontal cortex, and the Methods use a 10–20 EEG position to target it. But the Methods specify FP1, not the claimed right-sided FP2; the paper does not say the location is easily identified by anatomical landmarks or that it overlaps the right VMPFC. Page numbers are unavailable in our copy. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites [82] sourcePartly supported

  The Methods (§2.3.1.1, page unavailable) support locating a frontal-pole stimulation site with anatomical landmarks and the 10–20 EEG system. But the paper places the coil at Fp1, approximating the left frontal pole—not FP2 on the right—and does not establish overlap with the right VMPFC. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

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

The Beck Suicide Scale has Cronbach alpha=0.89 (very high) and strong predictive validity.

“Cronbach α=0.89 (very high), strong predictive validity [114]”

• cites [114] sourcePartly supported

  The Internal consistency section reports α=0.89 for the SSI-W among 1,764 psychiatric outpatients with suicidal ideation, not for the full sample or the SSI-C. The Introduction and Discussion report that the SSI-W predicted subsequent suicide in an earlier outpatient study, supporting predictive validity for that version. The claim omits these qualifications and presents both properties as applying to the Beck Suicide Scale generally. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

May combine two claims.

Many patients will require multiple medication trials and may take months to experience any symptomatic improvement.

“Furthermore, many patients will require multiple medication trials and may take months to experience any symptomatic improvement [36].”

• cites [36] sourceNot checked — no full text of the source

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

More than 400,000 new TBI diagnoses have occurred among US service members since the beginning of operations Enduring Freedom, Iraqi Freedom, and New Dawn, of which more than 80% are mild traumatic brain injury.

“These statistics are particularly concerning given that there have been >400,000 new TBI diagnoses among US service members since the beginning of operations Enduring Freedom, Iraqi Freedom, and New Dawn, of which >80% are mild traumatic brain injury (mTBI) [3].”

• cites [3] DOD TBI worldwide numbersHealth.mil2024-04-29https://health.mil/Military-Health-Topics/Centers-of-Excellence/Traumatic-Brain-Injury-Center-of-Excellence/DOD-TBI-Worldwide-NumbersNot matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

Negative urgency impulsivity is associated with excessive agitation, irritability, low moods, and a greater tendency for aggression toward oneself or others immediately following a negative event.

“It is associated with excessive agitation, irritability, low moods, and a greater tendency for aggression toward oneself or others immediately following a negative event [40].”

• cites [40] sourceNot checked — no full text of the source

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

In a large noninferiority study comparing iTBS and TMS, patients with treatment-resistant depression show similar safety and adverse event profiles and exhibit improvements in depressive symptoms to both interventions.

“In a large, noninferiority study comparing iTBS and TMS, patients with treatment-resistant depression show similar safety and adverse event (AE) profiles and exhibit improvements in their depressive symptoms to both interventions [29].”

• cites [29] sourceNot checked — no full text of the source

May combine two claims.

Comorbid conditions with mTBI include substance use disorders, PTSD, and depression.

“Comorbid conditions include substance use disorders, PTSD, and depression [66-68].”

• cites [66] sourceNot checked — no full text of the source
• cites [67] sourceNot checked — no full text of the source
• cites [68] sourceNot checked — no full text of the source

May combine two claims.

TBI, SI, impulsivity, and functional deficits are intertwined and should be considered in tandem.

“Given that TBI and impulsivity are both (1) independent risk factors for developing SI and (2) associated with impaired social and community functioning, it appears that TBI, SI, impulsivity, and functional deficits are intertwined and should be considered in tandem.”

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

Veterans with mTBI make up the majority, more than 80%, of the veteran population with TBI in the United States.

“Veterans with mTBI make up the majority (>80%) of the veteran population with TBI in the United States [3].”

• cites [3] DOD TBI worldwide numbersHealth.mil2024-04-29https://health.mil/Military-Health-Topics/Centers-of-Excellence/Traumatic-Brain-Injury-Center-of-Excellence/DOD-TBI-Worldwide-NumbersNot matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

Characteristics of negative urgency impulsivity can reduce quality of life and worsen community and social functioning, predisposing individuals to SI and SAs.

“These characteristics of negative urgency impulsivity can reduce the quality of life and worsen community and social functioning, predisposing individuals to SI and SAs (Figure 1) [46].”

• cites [46] Silver, JM, 2011, Textbook of Traumatic Brain Injury. 2nd editionNot checked yet

  Not checked in the free run.

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

TMS has demonstrated efficacy in the treatment of depression in large, multisite, sham-controlled trials.

“Seminal studies by George et al [19] demonstrated the efficacy of TMS in the treatment of depression in large, multisite sham-controlled trials.”

• cites [19] sourceNot checked — no full text of the source

May combine two claims.

This amount of iTBS stimulation appears to be well tolerated and shows a good effect on depressive symptoms, even in a treatment-refractory group.

“This amount of stimulation appears to be well tolerated and shows a good effect on depressive symptoms, even in a treatment-refractory group [58].”

• cites [58] sourceNot checked — no full text of the source

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

iTBS was first shown to treat depression in 2009 in a study by Holzer and Padberg.

“A second-generation form of TMS, intermittent theta burst stimulation (iTBS), was first shown to treat depression in 2009 in a study by Holzer and Padberg [28].”

• cites [28] sourceNot checked — no full text of the source

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

Veterans die by suicide at almost double the rate of civilians in the United States.

“Veterans die by suicide at almost double the rate of civilians in the United States [1].”

• cites [1] Ramchand, R, 2022, Rand Health QNot matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

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

TMS was subsequently approved by the FDA to treat treatment-resistant depression in 2008.

“TMS was subsequently approved by the FDA to treat treatment-resistant depression in 2008 [53-55].”

• cites [53] Repetitive transcranial magnetic stimulation (rTMS) systems - class II special controls guidance for industry and FDA staffFood and Drug Administration, USA2024-04-29https://www.fda.gov/medical-devices/guidance-documents-medical-devices-and-radiation-emitting-products/repetitive-transcranial-magnetic-stimulation-rtms-systems-class-ii-special-controls-guidanceNot matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites [54] FDA permits marketing of transcranial magnetic stimulation for treatment of obsessive-compulsive disorderFood and Drug Administration, USA20182024-04-29https://www.fda.gov/news-events/press-announcements/fda-permits-marketing-transcranial-magnetic-stimulation-treatment-obsessive-compulsive-disorderNot matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites [55] Coverage guidance for TMS for OCDClinical TMS Society2024-04-29https://www.clinicaltmssociety.org/sites/default/files/ctmss_recommended_ocd_coverage_policy_0.pdfNot matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

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

Between 16% and 20% of all operations Enduring Freedom, Iraqi Freedom, and New Dawn veterans have a history of mTBI, and among them, up to 22% report suicidal ideation.

“Overall, between 16% and 20% of all operations Enduring Freedom, Iraqi Freedom, and New Dawn veterans have a history of mTBI, and among them, up to 22% report suicidal ideation (SI) [4].”

• cites [4] sourceNot checked — no full text of the source

May combine two claims.

iTBS is a second-generation FDA-approved form of TMS designed to mimic endogenous brain rhythms with the added benefit of markedly reduced treatment time.

“iTBS is a second-generation FDA-approved form of TMS designed to mimic endogenous brain rhythms with the added benefit of markedly reduced treatment time [28,56].”

• cites [28] sourceNot checked — no full text of the source
• cites [56] sourceNot checked — no full text of the source

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

To ensure tolerability, stimulation intensity will begin at 60% to 70% of the motor threshold and will slowly increase as the patient tolerates to 110% of the patient's motor threshold over the first few treatment sessions.

“To ensure that the participants can tolerate the treatment, stimulation intensity will begin at 60% to 70% of the MT intensity and will slowly increase as the patient tolerates to 110% of the patient’s MT intensity over the first few treatment sessions [42].”

• cites [42] sourceNot checked — no full text of the source

Classified as probably not a substantial claim.

For safety, the study will exclude persons with contraindications to TMS or MRI because of increased risk of adverse events.

“For safety, we will exclude persons with contraindications to TMS or MRI because of increased risk of AEs.”

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

The study protocol was reviewed and approved by the Edward Hines, Jr. VA Hospital Institutional Review Board and the University of Illinois, Chicago Institutional Review Board.

“The study protocol was reviewed and approved by the Edward Hines, Jr. VA Hospital Institutional Review Board (Hines IRB number 1716074) and the University of Illinois, Chicago Institutional Review Board.”

• Also stated in: § Results · plain

  “This study protocol was approved by the Edward Hines, Jr. VA Hospital Institutional Review Board (Hines IRB number 14-003).”

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

The Alcohol Use Disorder Identification Test has AUROC=0.891 (high).

“AUROCk=0.891 (high) [101]”

• cites [101] sourceNot checked — no full text of the source

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

The PTSD Checklist for DSM-5 has Cronbach alpha=0.94 (very high) and test-retest reliability rtt=0.82 (high).

“Cronbach α=0.94 (very high) and test-retest reliability (rtt=0.82) (high) [116]”

• cites [116] sourceNot checked — no full text of the source

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

The Neurobehavioral Symptom Inventory has Cronbach alpha=0.81-0.96 (very high).

“Cronbach α=0.81-0.96 (very high) [98]”

• cites [98] sourceNot checked — no full text of the source

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

The Ohio State TBI Identification Method has interrater reliability greater than 90% (very high).

“Interrater reliability >90% (very high) [92]”

• cites [92] sourceNot checked — no full text of the source

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

A single unblinded study team member will determine which participants are randomly placed in the active or sham groups.

“A single unblinded study team member will determine which participants are randomly placed in the active or sham groups.”

May combine two claims.

By inducing modulation and neuroplasticity to the VMPFC and limbic system, iTBS at the frontal pole offers a promising means of mitigating impulsive behaviors and decreasing SI by increasing connectivity and undoing limbic damage caused by mTBI.

“By inducing modulation and neuroplasticity to the VMPFC and limbic system, iTBS at the frontal pole offers a promising means of mitigating impulsive behaviors and decreasing SI by increasing connectivity and undoing limbic damage caused by mTBI.”

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

Any seizure will result in stopping the intervention and withdrawal from the study.

“Any seizure will result in stopping the intervention and withdrawal from the study.”

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

The study will collect 10 validated, psychometric, quantitative outcome measures before, during, and after the intervention.

“We will collect 10 validated, psychometric, quantitative outcome measures before, during, and after the intervention.”

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

The Social and Occupational Functioning Assessment Scale has weighted K=0.95 (very high).

“Weighted K=0.95 (very high) [107]”

• cites [107] sourceNot checked — no full text of the source

Classified as probably not a substantial claim.

The study will exclude participants whose SI is active, with intent and plan, as they require emergency psychiatric intervention.

“We will also exclude participants whose SI is active, with intent and plan, as they require emergency psychiatric intervention.”

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

The Columbia Suicide Severity Rating Scale has internal validity a=0.95 and test-retest reliability rtt=0.90-1.0 (very high).

“Internal validity a=0.95 and test-retest reliability rtt=0.90-1.0 (very high) [93,94]”

• cites [93] sourceNot checked — no full text of the source
• cites [94] sourceNot checked — no full text of the source

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

The proposed study is a pilot, prospective, randomized, double-blinded, sham-controlled study to develop a frontal pole iTBS intervention.

“The proposed study is a pilot, prospective, randomized, double-blinded, sham-controlled study to develop a frontal pole iTBS intervention.”

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

Pain and tolerability measures will be completed at the end of every session to assess daily pain and session tolerability.

“Pain and tolerability measures will be completed at the end of every session to assess daily pain and session tolerability.”

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

All iTBS sessions will be videotaped to monitor for safety and allow for review in case of an adverse event.

“All iTBS sessions will be videotaped to monitor for safety and allow for review in case of an AE.”

Probably not a substantial claim: may not pass S4 (based).

mTBI must have occurred at least 1 year before enrollment to ensure that the injury has stabilized.

“mTBI must have occurred at least 1 year before enrollment to ensure that the injury has stabilized.”

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

Research staff will complete a TMS safety rating scale before and after every iTBS session to assess for changes from baseline for vital signs, sleep duration, fatigue level, recent seizures, and tinnitus.

“Research staff will complete a TMS safety rating scale before and after every iTBS session to assess for changes from baseline for vital signs, sleep duration, fatigue level, recent seizures, and tinnitus.”

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

Participants will be clinically monitored for seizure by trained research staff.

“Participants will be clinically monitored for seizure by trained research staff.”

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

The Veteran's RAND has Cronbach alpha=0.78-0.93 depending on the domain (high-very high).

“Cronbach α=0.78-0.93 depending on the domain (high-very high) [112]”

• cites [112] 36-item short form survey (SF-36) scoring instructionsRAND Corporation2024-07-16https://www.rand.org/health-care/surveys_tools/mos/36-item-short-form/scoring.htmlNot matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

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

This study does not select targets based on resting-state data.

“This study does not select targets based on resting-state data; however, in collecting these data in tandem using neuronavigation, we can potentially target more specific sites in the future.”

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

To enhance generalizability, the study will include veterans regardless of previous combat or deployment experience.

“To enhance generalizability, we will include veterans regardless of previous combat or deployment experience.”

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

Variability in baseline characteristics of the patient population may impact the study findings.

“Variability in the baseline characteristics of the patient population (ie, co-occurring psychiatric and somatic conditions, coadministration of other medications, etc) that are being studied in detail in this project may impact our findings.”

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

All analyses will be corrected for multiple comparisons using false-discovery rate correction.

“All analyses will be corrected for multiple comparisons using false-discovery rate correction.”

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

The Inventory of Depressive Symptomatology, Self-Report has Cronbach alpha=0.94 (very high) and test-retest reliability rtt=0.82 (high).

“Cronbach α=0.94 (very high) and test-retest reliability rtt=0.82 (high) [118]”

• cites [118] sourceNot checked — no full text of the source

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

In developing this protocol, the authors referenced the SPIRIT guidelines.

“In developing this protocol, we referenced the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines [85].”

• cites [85] sourceNot checked — no full text of the source

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

The analysis will adjust for a priori covariates including age, sex, and baseline psychiatric diagnoses.

“We will adjust for a priori covariates, including age, sex, and baseline psychiatric diagnoses.”

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

The study is registered on ClinicalTrials.gov (NCT05647044).

“The study is registered on ClinicalTrials.gov (NCT05647044).”

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

The study is designed in accordance with the ethical standards of the US VA Office of Research and Development, based on those from the Declaration of Helsinki, the Belmont Report, US Common Rule and Regulations from the Council for International Organizations of Medical Sciences.

“This study is designed in accordance with the ethical standards of the US VA Office of Research and Development, based on those from the Declaration of Helsinki, the Belmont Report, US Common Rule and Regulations from the Council for International Organizations of Medical Sciences.”

May combine two claims.

The sham stimulation looks, sounds, and feels like active stimulation.

“Thus, the sham stimulation looks, sounds, and feels like active stimulation.”

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

The Buss-Perry Aggressiveness Scale has test-retest reliability rtt=0.80 (high) and Cronbach alpha=0.68-0.8 for each subscale (moderate-high).

“Test-retest reliability rtt=0.80 (high), Cronbach α=0.68-0.8 for each subscale (moderate-high) [108]”

• cites [108] sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S4 (based). May combine two claims.

The sham coil and scalp electrodes will be placed in the same location for all participants and will mimic the sensation produced by the active coil but will not alter brain physiology.

“The sham coil and scalp electrodes will be placed in the same location for all participants and will mimic the sensation produced by the active coil but will not alter brain physiology.”

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

A thorough chart review will be completed to cross-reference current medications with study eligibility criteria to identify antiepileptics or medications that could lower the seizure threshold.

“A thorough chart review will be completed to cross-reference current medications with study eligibility criteria to identify antiepileptics or medications that could lower the seizure threshold.”

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

The Stroop Color & Word Test has reliability estimates ranging from a=0.83 to a=0.91 and test-retest reliability ranging from rtt=0.79 to rtt=0.97 (all high-very high).

“Reliability estimates range from a=0.83 to a=0.91 and test-retest reliability ranges from rtt=0.79 to rtt=0.97 (all high-very high) [124]”

• cites [124] sourceNot checked — no full text of the source

May combine two claims.

The small sample size reduces the study power, which may limit the detection of statistically significant outcome differences.

“The small sample size reduces the study power, which may limit the detection of statistically significant outcome differences.”

Classified as probably not a substantial claim.

The active and sham iTBS coils are visually identical.

“The coil is identical visually for the sham and active conditions.”

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

The Localite neuronavigation system and an MRI instrument marker will be used at every iTBS session to ensure precise and repeatable coil positioning over the frontal pole FP2 site.

“To ensure precise and repeatable coil positioning over the frontal pole FP2 site, the Localite (neuronavigation) system and an MRI instrument marker will be used at every iTBS session.”

May combine two claims.

The total sample size will be 56 with 28 in the active iTBS group and 28 in the sham iTBS group.

“Thus, our total sample size will be 56 with 28 in the active iTBS group and 28 in the sham iTBS group.”

Classified as probably not a substantial claim.

Veterans and researchers will wear headphones connected to a noise generator during treatment to hear active iTBS for both conditions, thereby maintaining the blind.

“Veterans and researchers will wear headphones connected to the noise generator during treatment to hear active iTBS for both conditions, thereby maintaining the blind.”