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PreprintCited by 0Traumatic Brain Injury ResearchTranscranial Magnetic Stimulation StudiesTraumatic Brain Injury and Neurovascular Disturbances

Functional MRI Guided Accelerated Intermittent Theta Burst Stimulation for Chronic Post-Concussive Syndrome: A Feasibility and Efficacy Study

Open access
Bartholomeusz, Evan J., Fong, Alina K., Tervort, Thomas J., Gaufin, Lynn M., Allen, Mark D.·2025·medRxiv
DOI 10.1101/2025.10.08.25336734
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Abstract

Post concussive syndrome (PCS) affects 10-15% of people with mTBI (concussion). Some of these symptoms persist for months or years after the original injury. Currently, few effective interventions exist for PCS. Previous studies have explored transcranial magnetic stimulation (TMS) as an interventional measure for PCS. TMS is also demonstrated to be an effective treatment for patients with depression and anxiety, which are often comorbid in patients with chronic concussion-related symptoms. This exploratory study aims to examine the feasibility and efficacy of a rapid, accelerated intermittent theta burst stimulation (iTBS) TMS treatment protocol to alleviate symptoms in patients with chronic PCS.

AI snapshot

Written from the paper’s full text.

TL;DR

In this single-arm, open-label pilot, accelerated fcMRI-guided intermittent theta burst stimulation (iTBS) to the anterior prefrontal cortex was feasible and well tolerated in 11 participants with chronic post-concussive syndrome. Significant improvements appeared in task-related fMRI connectivity and self-reported PCS, depression, and anxiety symptoms, but the uncontrolled design limits efficacy conclusions.

Key findings

  • Feasibility/tolerability: 11 participants enrolled and completed treatment. Side effects included scalp sensitivity, facial muscle fatigue, headache, and temporarily worsened PCSS scores after sessions, but all patients recovered before the next day’s treatment. Mean session intensity was 112.48% rMT (range 98–120%).
  • PCSS scores improved from baseline 54.25 (SD = 31.04) to post-treatment 22.00 (SD = 13.50) and 1–4 weeks post-treatment 19.25 (SD = 15.10); ANOVA F(2,21) = 6.61, p = .006; baseline-to-post t = 3.19, p = .008; baseline-to-follow-up t = 2.81, p = .013. The paper reports 63% mean symptom reduction immediately post-treatment and 62% at 1–4 weeks, with 7 participants showing >50% immediate reduction.
  • BDI scores changed from baseline 21.5 (SD = 10.94) to post-treatment 12.87 (SD = 10.38) and 1–4 weeks 13.12 (SD = 11.35); baseline-to-post t = 2.25, p = .03; baseline-to-follow-up t = 2.74, p = .014. BAI scores changed from baseline 22.75 (SD = 15.83) to post-treatment 10.62 (SD = 9.37) and 1–4 weeks 8.62 (SD = 5.78); ANOVA F(2,21) = 3.77, p = .04; baseline-to-post t = 1.89, p = .05; baseline-to-follow-up t = 3.08, p = .009.
  • Task-related fMRI fNCI scores improved: brain region scores decreased by an average of 51.6%, from baseline mean 2.75 (SD = 1.07) to post-treatment 1.21 (SD = 0.34), t = 4.72, p = .0004; functional connectivity scores decreased by an average of 56.9%, from baseline mean 1.83 (SD = 0.12) to post-treatment 0.79 (SD = 0.16), t = 7.11, p < .0001. All participants showed ≥40% reductions in functional connectivity scores.

Methods

  • Design: exploratory, single-arm, open-label pilot study; 17 screened, 12 eligible, 11 enrolled and completed treatment (4 male, 7 female; ages 16–72). Participants were recruited primarily from referrals to Neural Effects/Cognitive FX, including two with acute (<3 months) concussion symptoms. Eight participants completed BDI, BAI, and PCSS surveys.
  • Intervention: resting-state fcMRI was used to personalize a left dorsolateral/anterior prefrontal target anti-correlated with the DMN and positively correlated with dACC/CCN nodes. iTBS was delivered at 120% rMT target intensity using Magstim Horizon 3.0: 1200 pulses/session, 5 sessions/day, 30-minute intervals, over 3 consecutive days (18,000 total pulses; exceptions included 15,600 pulses or non-consecutive days). Mean session intensity was 112.48% rMT.
  • Measures/analysis: PCSS, BDI, and BAI at baseline, immediately post-treatment, and 1–4 weeks post-treatment; task-related fMRI fNCI pre- and post-treatment compared against a normative database of 270 healthy controls. Outcomes analyzed with one-way ANOVA and post-hoc paired t-tests; fNCI values reported as z-scores.

Limitations

  • Stated: small, heterogeneous sample limits generalizability; no control group and all participants/administrators were aware of treatment; follow-up was limited and varied by weeks. The authors recommend a randomized controlled trial with longer follow-up.
  • Evident from the text: the single-arm open-label design cannot establish causality; symptom survey follow-up was incomplete (6 participants at 1 week, 2 at 4 weeks); treatment intensity and pulse protocols varied across some participants; and all authors are employees of Cognitive FX, which funded and conducted the study, a declared potential conflict of interest.

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

Integrity signals

Registry

Crossref · 10.1101/2025.10.08.25336734

Cites

20 of 20 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

12 of 18 cited sources checked · 1 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    Persistent post-concussive symptoms are associated with disruptions in large-scale functional brain networks.

    “The rationale for applying TMS, and specifically iTBS, to PCS stems from converging evidence suggesting that persistent post-concussive symptoms are associated with disruptions in largescale functional brain networks.”
    Quote in the paperSubstantial claim3 of 3 sources checked
    • cites [8] source

      The Discussion and Conclusion (pages not provided) link disrupted connectivity within and between large-scale networks to cognitive and somatic symptoms after concussion. However, the study found the symptom–connectivity relationship was strongest acutely, about 48 hours after injury; it does not establish that persistent post-concussive symptoms are associated with those disruptions. The Conclusion notes that some connectivity disruptions remained after clinical recovery even when symptoms returned to baseline. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [9] source

      The Discussion reports that disrupted global resting-state alpha-band functional connectivity predicts fatigue after TBI. However, the study examines fatigue in chronic TBI patients, not persistent post-concussive symptoms as a whole; the Participants section does not identify a concussion-specific cohort. Page numbers are unavailable in our copy. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites [12] source

      The “A network perspective” section describes large-scale functional brain networks and their roles in cognition, but does not link network disruptions to persistent post-concussive symptoms. Searches for concussion, PCS, and traumatic brain injury found no passage addressing that association; the copy provides no page number for the section. (LLM, conf=0.75)

      Experimental — accuracy not yet measured
  • Premisecitation

    Reduced activity or connectivity within the CCN/CEN or between the CCN/CEN and other networks is associated with cognitive deficits in PCS.

    “Cognitive Control Network (CCN) / Central Executive Network (CEN): Involved in goaldirected attention, working memory, and executive functions, reduced activity or connectivity within the CCN/CEN or between the CCN/CEN and other networks is often associated with cognitive deficits in PCS 9”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [9] source

      The Introduction (page unavailable) reports reduced functional connectivity after moderate-to-severe TBI, and the Discussion (page unavailable) suggests that network alterations may be linked to cognitive disturbances. Neither passage identifies the CCN/CEN or establishes that reduced connectivity in or between those networks is associated with cognitive deficits in PCS. (LLM, conf=0.78)

      Experimental — accuracy not yet measured
  • Premisecitation

    iTBS protocols generally induce facilitatory effects on cortical excitability, promoting mechanisms akin to long-term potentiation.

    “Preclinical and human studies suggest that iTBS protocols generally induce facilitatory ePects on cortical excitability, promoting mechanisms akin to long-term potentiation (LTP) 6”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [6] source

      The indexed passages discuss synaptic LTP and cite work on hippocampal theta-burst pairing potentiation, but do not address intermittent theta-burst stimulation (iTBS) or its effects on cortical excitability. Searches for iTBS, intermittent theta-burst stimulation, and cortical excitability found no passage supporting the attributed claim; the available passages are labeled Abstract, with no page given. (LLM, conf=0.76)

      Experimental — accuracy not yet measured
  • Premisecitation

    Dysfunction in the salience network is linked to fatigue, affective symptoms, and cognitive difficulties post-concussion.

    “Salience Network (SN): Crucial for detecting relevant internal and external stimuli and switching between the DMN and CCN/CEN, dysfunction in the SN (often involving the dorsal anterior cingulate cortex (dACC) and insula) has been linked to fatigue, aPective symptoms, and cognitive diPiculties post-concussion 12 13 .”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [12] source

      The sections on functional connectivity and the salience network describe an anterior-insula/dorsal-ACC network that detects relevant stimuli and helps coordinate other networks. The cited paper does not link salience-network dysfunction specifically to fatigue, affective symptoms, or cognitive difficulties after concussion; searches for post-concussion symptoms and traumatic brain injury found no such passage. Page numbers are unavailable in our copy. (LLM, conf=0.86)

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

      The Functional significance section (page not specified in our copy) describes a salience network anchored by the dACC and frontoinsula that identifies relevant stimuli. The Abstract reports an association between salience-network connectivity and prescan anxiety. Neither passage links salience-network dysfunction to fatigue, affective symptoms, or cognitive difficulties after concussion; the copy also does not establish that this network switches between the DMN and executive-control network. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
  • Interpretationown data

    Accelerated iTBS TMS applied to the correct location could have a normalizing effect on compensatory brain network inefficiencies typically seen in PCS patients.

    “suggests that accelerated iTBS TMS applied to the correct location could have a normalizing ePect on compensatory brain network inePiciencies typically seen in PCS patients 9”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [9] source

      The Discussion (page not available) reports compensatory changes in brain connectivity after TBI and proposes non-invasive neuromodulation as a possible way to influence network interactions. It does not specifically assess accelerated iTBS, identify a treatment location, or establish a normalizing effect in PCS patients. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • Rests on an assumption: The improvements in symptoms and fNCI scores observed in this uncontrolled pilot are attributable to the iTBS intervention rather than to placebo, natural recovery, or other factors.
  • May combine two claims. 30
  • Classified as probably not a substantial claim. 18
  • The quote only partly states this claim. 1

  • May combine two claims.

    Premisecitation

    Alterations in DMN connectivity are commonly observed post-mTBI and linked to cognitive complaints.

    “Default Mode Network (DMN): Implicated in self-referential thought and introspection, alterations in DMN connectivity (often increased intra-network connectivity or altered connectivity with other networks) are commonly observed post-mTBI and linked to cognitive complaints 89 10 11 .”
    Quote in the paperSubstantial claim3 of 3 sources checked
    • cites [8] source
    • cites [9] source

      The Discussion (page unavailable) reports altered connectivity involving cortical midline regions that are part of the DMN and suggests these alterations may relate to complex cognitive disturbances. It does not establish that DMN connectivity changes are common after mild TBI or that they are linked specifically to cognitive complaints; its observed connectivity abnormality was confined to TBI patients with fatigue. (LLM, conf=0.83)

      Experimental — accuracy not yet measured
    • cites [10] source

      The Introduction and ‘Differences in effective connectivity between depressed patients and controls’ discuss DMN connectivity in depression, not after mild traumatic brain injury. Searches for mTBI, concussion, and cognitive complaints found no passage addressing the claimed post-mTBI association. (LLM, conf=0.76)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingown data

    Patients demonstrated significantly reduced self-reported measures of PCS severity, anxiety, and depression symptoms.

    “Patients also demonstrated significantly reduced self-reported measures of PCS severity, anxiety, and depression symptoms.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    A dramatic reduction in fNCI scores occurred across all patients, particularly inter-region functional connectivity.

    “Our most significant finding was a dramatic reduction in fNCI scores across all patients, particularly inter-region functional connectivity.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    During the 1-4 week follow-up period, four participants reported a further (>40%) reduction in symptoms, while remaining participants reported little change or moderate increase of symptoms.

    “During the 1-4 week follow-up period, four participants reported a further (>40%) reduction in symptoms, while remaining participants reported little change or moderate increase of symptoms.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Eleven participants (four male, seven female) with history of concussion/mTBI were recruited, ranging from 16-72 years of age.

    “Eleven participants, four male and seven female, with history of concussion/mTBI were recruited for this study.Patients ranged from 16-72 years of age.”
    Quote in the paperNot a substantial claim

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

    Findingnone given

    The remaining eight participants were treated and administered pre- and post-task-related fMRI scans, BDI, BAI, and PCSS survey measures.

    “The remaining eight participants were treated and administered pre-and post-task-related fMRI scans, BDI, BAI, and PCSS survey measures.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Mean BDI scores were 21.5 (SD = 10.94) at baseline, 12.87 (SD = 10.38) post-treatment, and 13.12 (SD = 11.35) at 1-4 weeks post-treatment.

    “BDI Mean BDI scores at three measurement points were as follows, Baseline: 21.5 (SD = 10.94);Post-Treatment: 12.87 (SD = 10.38);1-4 Weeks Post Treatment: 13.12 (SD = 11.35),see FIGURE 2.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    For Functional Connectivity scores, the Baseline mean was 1.83 (SD = 0.12) and the Post-Treatment mean was 0.79 (SD = 0.16).

    “For Functional Connectivity scores, the Baseline mean was 1.83 (SD = 0.12), and the Post-Treatment mean was 0.79 (SD = 0.16).”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    Post-hoc paired t-test analyses revealed a significant BAI difference between Baseline and 1-4 Weeks Post Treatment (t = 3.08; p = .009).

    “a significant diPerence between Baseline and 1-4 Weeks Post Treatment (t = 3.08; p =.009)”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Side effects included scalp sensitivity during and immediately after treatment, facial muscle fatigue, headache persisting through inter-treatment intervals, and temporarily worsened self-reported PCSS scores immediately following each treatment session.

    “Side ePects included scalp sensitivity during and immediately after treatment, facial muscle fatigue, headache persisting through inter-treatment intervals, and temporarily worsened self-reported PCSS scores immediately following each treatment session.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Of participants included in the surveyed sample, 6 provided follow-up survey scores at 1-week post-treatment and 2 provided follow-up survey scores at 4 weeks post-treatment.

    “Of participants included in the surveyed sample, 6 provided follow-up survey scores at 1-week post-treatment, while 2 provided follow-up survey scores at 4 weeks post-treatment.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingnone given

    Some participants reported moderate improvement of symptoms during and immediately following treatment but later reported that symptoms had improved considerably beyond the scheduled follow-up period.

    “Some participants reported moderate improvement of symptoms during and immediately following treatment but later reported that symptoms had improved considerably beyond our scheduled follow up period.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Mean BAI scores were 22.75 (SD = 15.83) at baseline, 10.62 (SD = 9.37) post-treatment, and 8.62 (SD = 5.78) at 1-4 weeks post-treatment.

    “BAI Mean BAI scores at three measurement points were as follows, Baseline: 22.75 (SD = 15.83);Post-Treatment: 10.62 (SD = 9.37); 1-4 Weeks Post Treatment: 8.62 (SD = 5.78), see FIGURE 3.”
    Quote in the paperSubstantial claim

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

    Findingown data

    Three initial participants were treated and reported good outcomes; they received pre- and post-task-related fMRI scans without BDI, BAI, or PCSS surveys.

    “Three initial participants were treated and reported good outcomes.These preliminary participants were administered pre-and post-task-related fMRI scans, without BDI, BAI, or PCSS surveys.”
    Quote in the paperNot a substantial claim

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

    Findingreasoning

    Average treatment intensity across all sessions varied between 98% and 120% rMT, with a mean session treatment intensity of 112.48% rMT.

    “Accordingly, average treatment intensity across all sessions varied between 98% and 120% rMT, with a mean session treatment intensity of 112.48% rMT.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    All participants, regardless of self-reported symptom measures, showed a trend towards normal intra-region metabolism (t = 4.72) and normal inter-region connectivity (t = 7.11).

    “All participants, regardless of self-reported symptom measures, showed a dramatic trend towards normal intra-region metabolism (t=4.72) and normal inter-region connectivity (t=7.11).”
    Quote in the paperSubstantial claim

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

    Findingown data

    Two participants with acute (<3 months since injury) concussion symptoms were also included.

    “Two participants with acute (<3 months since injury) concussion symptoms were also included.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    Of 17 initially screened participants, 12 were eligible and 11 chose to enroll and complete treatment.

    “17 total participants were initially screened for participation in this study.Of those, 12 were eligible, and 11 chose to enroll and complete treatment.”
    Quote in the paperNot a substantial claim

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

    Findingown data

    18,000 total iTBS pulses were administered over 3 consecutive days, with exceptions: one participant received 18,000 pulses on 3 non-consecutive days within a 6-day period, one received 15,600 pulses over 3 consecutive days, and one received 15,600 pulses over 3 non-consecutive days within a 5-day period.

    “Total Pulse and Time Sequence 18,000 total iTBS pulses were administered over 3 consecutive days, with the following exceptions: one participant received 18,000 total iTBS pulses administered on 3 non-consecutive days within a 6-day period, one participant received 15,600 total iTBS pulses administered over 3 consecutive days, and one participant received 15,600 total iTBS pulses administered over”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Most participants reported substantial symptom abatement after one day of treatment, with incremental improvements reported after each subsequent day of treatment.

    “Most participants reported substantial symptom abatement after one day of treatment, with incremental improvements reported after each subsequent day of treatment.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Mean PCSS scores were 54.25 (SD = 31.04) at baseline, 22.00 (SD = 13.50) post-treatment, and 19.25 (SD = 15.10) at 1-4 weeks post-treatment.

    “Mean PCSS scores at three measurement points were as follows, Baseline: 54.25 (SD = 31.04);Post-Treatment: 22.00 (SD = 13.50);1-4 Weeks Post Treatment: 19.25 (SD = 15.10),see FIGURE 1.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Patients demonstrated significant improvement in task-related brain region activation levels and inter-region functional connectivity compared to healthy controls.

    “Patients demonstrated significant improvement in task-related brain region activation levels and inter-region functional connectivity compared to healthy controls.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Some patients who showed substantial reduction in PCS symptoms immediately after treatment exhibited exacerbated symptoms 1-2 weeks post-treatment, although fNCI scores for the same patients were still significantly reduced.

    “Interestingly, some patients who showed substantial reduction in PCS symptoms immediately after treatment exhibited exacerbated symptoms 1-2 weeks post-treatment, although fNCI scores for the same patients were still significantly reduced”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Patients exhibited a significant (p < 0.01) decrease in anxiety symptoms 1-4 weeks post-treatment (60% mean symptom reduction, SD = 21%; 14.13 mean BAI score decrease, SD = 12.2), but not immediately after treatment.

    “Patients exhibited a significant (p<0.01)decrease in anxiety symptoms 1-4 weeks post-treatment (60% mean symptom reduction, SD=21%) (14.13 mean BAI score decrease, SD=12.2),but not immediately after treatment.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Patients exhibited a significant (p < 0.03) decrease in depression symptoms immediately after treatment (34% mean symptom reduction, SD = 40%; 8.63 mean BDI score decrease, SD = 10.15) and 1-4 weeks post-treatment (8.38 mean BDI score decrease, SD = 8.09).

    “Conversely, patients exhibited a significant (p<0.03)decrease in depression symptoms immediately after treatment (34% mean symptom reduction, SD=40%) (8.63 mean BDI score decrease, SD=10.15) and 1-4 weeks post-treatment (8.38 mean BDI score decrease, SD=8.09).”
    Quote in the paperSubstantial claim

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

    Premisenone given

    Current standard treatment for PCS lacks definitive, universally effective interventions specifically approved for this condition.

    “Despite the significant burden imposed by Post-Concussive Syndrome (PCS), current standard treatment lacks definitive, universally ePective interventions specifically approved for this condition.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    iTBS has received FDA approval for the treatment of Major Depressive Disorder.

    “iTBS has gained significant attention, notably receiving FDA approval for the treatment of Major Depressive Disorder 7 .”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [7] source

  • May combine two claims.

    Interpretationown data

    Improvements across all measures were evident immediately following TMS intervention and persisted over 1-4 weeks after concluding treatment.

    “Improvements across all measures were evident immediately following TMS intervention and persisted over 1-4 weeks after concluding treatment.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    Given the exploratory nature and lack of a control condition, the findings are intended to inform the design of future, more definitive randomized controlled trials.

    “Given the exploratory nature and lack of a control condition, the findings are intended to inform the design of future, more definitive randomized controlled trials.”
    Quote in the paperSubstantial claim

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

    Interpretationnone given

    This intervention is personalized to each patient.

    “is personalized to each patient”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    This intervention requires relatively little time in-clinic compared to other TMS interventions.

    “requires relatively little time in-clinic compared to other TMS interventions”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    A brief intervention of iTBS TMS administered over 3 days is a feasible intervention to alleviate symptoms in patients with chronic PCS.

    “This pilot study demonstrates that a brief intervention of iTBS TMS, administered over 3 days, is a feasible intervention to alleviate symptoms in patients with chronic PCS and warrants further research.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The improvements in symptoms and fNCI scores observed in this uncontrolled pilot are attributable to the iTBS intervention rather than to placebo, natural recovery, or other factors.

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    The fNCI tasks were developed with the intent to activate a wide range of functional brain regions and networks sufficient to detect differences between individuals with no history of significant neurological or psychiatric dysfunction and those with a history of mild traumatic brain injury.

    “The tasks were developed with the intent to activate a wide range of functional brain regions and engage a wide range of functional networks, in a manner that is suPicient to detect diPerences between individuals with no history of significant neurological or psychiatric dysfunction, and those with a history of mild traumatic brain injury.”
    Quote in the paperSubstantial claim

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

    Study design and conductcitation

    The fNCI assessment protocol combines the validity of conventional neuropsychological testing standards with the reliability and objectivity of informational data output provided by fMRI.

    “The fNCI assessment protocol combines the validity of conventional neuropsychological testing standards with the reliability and objectivity of informational data output provided by fMRI.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Epps and Allen 15

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

  • May combine two claims.

    Study design and conductreasoning

    This pilot study included no control groups, and accordingly all participants and administrators were aware of the treatment being delivered.

    “this pilot study included no control groups; accordingly, all participants and administrators were aware of the treatment being delivered.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductnone given

    The follow-up period for participants was limited and varied by a matter of weeks between some patients.

    “our follow-up period for participants was limited and varied by a matter of weeks between some patients.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S4 (based).

    Interpretationreasoning

    By correcting maladaptive neural patterns introduced by mTBI via fMRI-guided accelerated TMS, patients may then benefit from other traditional interventions for PCS to which they may have been previously unresponsive.

    “We propose that by correcting maladaptive neural patterns introduced by mTBI via fMRI-guided accelerated TMS, patients may then benefit from other traditional interventions for PCS to which they may have been previously unresponsive.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The improvements in symptoms and fNCI scores observed in this uncontrolled pilot are attributable to the iTBS intervention rather than to placebo, natural recovery, or other factors.

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

    Study design and conductown data

    Anderson-Darling sample-size adjusted tests for normality determined the distributions of each of the 62 functional regions to be sufficiently normal, with estimates ranging from moderate (A2* = 0.59, p = 0.11) to high (A2* = 0.18, p = 0.91).

    “Anderson-Darling sample-size adjusted tests for normality determined the distributions of each of the 62 regions to be suPiciently normal, with estimates ranging from moderate (A2* = 0.59, p = 0.11) to high (A2* = 0.18, p = 0.91).”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    No head movement exceeded 1 mm translation or 1° rotation displacement.

    “No head movement exceeded 1 mm translation or 1° rotation displacement.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    The novel approach offers rapid relief from chronic concussion symptoms and significantly reduces maladaptive inter-region connectivity issues associated with long-term PCS symptoms.

    “Our novel approach oPers rapid relief from chronic concussion symptoms, and significantly reduces maladaptive inter-region connectivity issues associated with long-term PCS symptoms.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The improvements in symptoms and fNCI scores observed in this uncontrolled pilot are attributable to the iTBS intervention rather than to placebo, natural recovery, or other factors.

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    A sample of 270 healthy control volunteers were scanned on the fNCI protocols to provide a normative context to evaluate brain activation levels and functional network connectivity in brain-injured patients.

    “A sample of 270 healthy control volunteers were scanned on the fNCI protocols to provide a normative context to evaluate brain activation levels and functional network connectivity in brain-injured patients.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Accelerated iTBS TMS rapidly induces metabolic and connective changes within participants' brains, an effect that persists beyond conclusion of treatment.

    “Data from fNCI assessments suggest that accelerated iTBS TMS rapidly induces metabolic and connective changes within participants' brains, an ePect that persists beyond conclusion of treatment.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The improvements in symptoms and fNCI scores observed in this uncontrolled pilot are attributable to the iTBS intervention rather than to placebo, natural recovery, or other factors.
42 of 42

  • The paper relies on this without support.

    TMS is an effective treatment for patients with depression and anxiety, which are often comorbid in patients with chronic concussion-related symptoms.

    “TMS is also demonstrated to be an ePective treatment for patients with depression and anxiety, which are often comorbid in patients with chronic concussion-related symptoms.”

  • The paper relies on this without support.

    The anterior prefrontal cortex, particularly the middle frontal gyrus of the dorsolateral prefrontal cortex, is a critical hub within the CCN, playing key roles in executive functions, working memory, emotional regulation, and cognitive control.

    “The anterior prefrontal cortex (aPFC), particularly the middle frontal gyrus of the dorsolateral prefrontal cortex (DLPFC), is a critical hub within the CCN, playing a key role in executive functions, working memory, emotional regulation, and cognitive control -functions frequently impaired in PCS.”

  • The paper relies on this without support.

    The DLPFC exhibits significant functional connections with both the DMN (inhibitory) and SN/dACC (excitatory).

    “Furthermore, the DLPFC exhibits significant functional connections with both the DMN (inhibitory) and SN/dACC (excitatory).”

  • The paper relies on this without support.

    The sample of 270 healthy control volunteers provides a valid normative context for evaluating brain activation levels and functional network connectivity in brain-injured patients.

    “A sample of 270 healthy control volunteers were scanned on the fNCI protocols to provide a normative context to evaluate brain activation levels and functional network connectivity in brain-injured patients.”

  • The paper relies on this without support.

    The improvements in symptoms and fNCI scores observed in this uncontrolled pilot are attributable to the iTBS intervention rather than to placebo, natural recovery, or other factors.

    “Our novel target identification method coupled with imaging-guided targeting for treatment led to demonstrably improved interregional functional connectivity across all patients.”
    “Data from fNCI assessments suggest that accelerated iTBS TMS rapidly induces metabolic and connective changes within participants' brains, an ePect that persists beyond conclusion of treatment.”
5 of 5

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Immediate anxiety improvement is both significant and absent

    Major

    The BAI results call the baseline-to-post-treatment difference significant, whereas the outcomes summary says the significant decrease in anxiety occurred at follow-up but not immediately after treatment.

1 of 1

Cites

Flagged first, then by citations

Authors
Bartholomeusz, E. J., Fong, A. K., Tervort, T. J., Gaufin, L. M., & Allen, M. D.
Corresponding author
Allen, Mark D.
Venue
medRxiv
Publisher
openRxiv
Published
2025-10-13
DOI
10.1101/2025.10.08.25336734
OpenAlex
W4415135005
Semantic Scholar
cf4b0d81252c094e0bfee67c2c088db91c3733ca
Cited by
0
References
20
Type
posted content
Language
en
Open access
Licence
Locations
medRxiv (acceptedVersion, cc-by)
Topics
  • Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
  • Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
  • Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
Keywords
post-concussion syndrome, intermittent theta burst stimulation, transcranial magnetic stimulation, mild traumatic brain injury, comorbid depression, anxiety comorbidity, treatment efficacy, feasibility

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.

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