Repetitive Transcranial Magnetic Stimulation for Depression and Posttraumatic Stress Disorder in Veterans With Mild Traumatic Brain Injury

Philip, Noah S.; Ramanathan, Dhakshin; Gamboa, Bruno; Brennan, McKenna C.; Kozel, F. Andrew; Lazzeroni, Laura C.; Madore, Michelle

doi:10.1016/j.neurom.2022.11.015

Cited by 11 publications

(4 citation statements)

References 35 publications

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“…There is evidence that 1 Hz stimulation to the right dlPFC can reduce anxiety symptoms in depressed individuals. There is also some evidence that 5 Hz and iTBS to the right dlPFC can improve symptoms of PTSD [55][56][57][58][59][60][61]. While there is no clear-cut relationship between stimulation type and excitability, it is thought that 1 Hz is potentially inhibitory, while 5 Hz and iTBS are potentially excitatory.…”

Section: Discussionmentioning

confidence: 99%

Interleaved TMS/fMRI shows that threat decreases dlPFC-mediated top-down regulation of emotion processing

Patel,

Teferi,

Gura

et al. 2024

NPP—Digit Psychiatry Neurosci

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The dorsolateral prefrontal cortex (dlPFC) is thought to be a key site in the brain’s cognitive control network, supporting cognitive processes like attention and working memory [1–7]. There is also evidence that the dlPFC is engaged during anxiety regulation tasks, suggesting that anxiety regulation may be mediated in part by dlPFC activity [8–15]. However, the degree to which these two domains of processing overlap is unclear. Therefore, in the current study, we tested the hypothesis that the dlPFC regulates brain regions critical for the expression of anxiety. To do so, we used interleaved TMS/fMRI to record TMS-evoked BOLD responses during periods of threat compared to periods of safety. We hypothesized that TMS pulses would reduce activity in anxiety expression regions during threat. Forty-four healthy controls (no current or history of psychiatric disorders) were recruited to take part in a broader study. Participants completed the neutral, predictable, and unpredictable (NPU) threat task while receiving TMS pulses to either the right dlPFC or a control region. A whole brain analysis identified regions showing significant BOLD responses evoked by dlPFC stimulation. We then extracted these responses and compared those evoked during safe blocks to those evoked during unpredictable threat. We found that responses in the left insula (LI), right sensory/motor cortex (RSM), and a region encompassing the bilateral SMA regions (BSMA) showed significantly different responses during the safe blocks compare to the threat. During the safe periods, these regions showed significant BOLD deactivations. These deactivations were reduced during the threat blocks. Overall, these findings are largely consistent with the hypothesis that the dlPFC plays a role in the top-down control of emotion and suggest that dlPFC activity reduces downstream activity in emotional expression regions, but that this effect is reduced under threat.

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Section: Discussionmentioning

confidence: 99%

Interleaved TMS/fMRI shows that threat decreases dlPFC-mediated top-down regulation of emotion processing

Patel,

Teferi,

Gura

et al. 2024

NPP—Digit Psychiatry Neurosci

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“…TMS has demonstrated efficacy in treating several post-mTBI sequelae and related neuropsychiatric conditions, including depression, posttraumatic stress disorder (PTSD), cognitive deficits, and chronic pain/headaches [36][37][38][39]. TMS also improves PTSD symptoms among those with cooccurring mTBI [40,41]. Further, multiple studies and meta-analyses demonstrate that TMS, administered to a variety of anatomical brain locations, including the DLPFC [42], does not induce more significant numbers of adverse events among individuals with mTBI than among individuals without mTBI [36,38,43].…”

Section: Tms As a Treatment For Tbi Sequelaementioning

confidence: 99%

“…We will use a T1 MRI to localize the frontal polar cortex (FP) stimulation site. This region will be easily located using anatomical landmarks [40,63] and is correlated with electrode FP2 on an electroencephalogram (EEG), a region overlapping with the right VMPFC. 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.…”

Section: Experimental Intervention Itbs Interventionmentioning

confidence: 99%

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 (Preprint)

Bernanke,

Hasley,

Sabetfakhri

et al. 2024

Preprint

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BACKGROUND Suicide remains a leading cause of death among Veterans, and mild traumatic brain injury (mTBI) increases the risk of suicidal ideation and suicide attempts (SI/SA). mTBI worsens impulsivity and contributes to poor social and occupational functioning, which further increasing the risk of SI/SA. Repetitive transcranial magnetic stimulation (TMS) is a neuromodulation treatment approach designed to mimic endogenous brain rhythms. Intermittent theta burst stimulation (iTBS) is a "second-generation" form of TMS that is safe, shorter in duration, displays a minimal side effect profile, and is a promising treatment approach for impulsivity in mTBI. Our novel treatment uses frontal pole stimulation to target the ventromedial prefrontal cortex (VMPFC) and may reduce impulsivity by strengthening functional connectivity between the limbic system and frontal cortex, potentially saving lives. OBJECTIVE The objectives of this study are to (1) develop an iTBS intervention for individuals with mTBI and SI, (2) assess the feasibility and tolerability of the intervention, and (3) gather preliminary clinical outcome data on SI, impulsivity, and functioning that will guide future studies. METHODS This is a pilot, double-blinded, randomized controlled trial. In developing this protocol, we referenced SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials). We will enroll 50 subjects (25 active iTBS and 25 sham iTBS). The iTBS intervention will be performed daily, five days a week, for two weeks. We will collect quantitative outcome measures before and after the intervention. Measures included will assess functioning (Social and Occupational Functioning Assessment Scale (SOFAS), Veteran RAND-36), impulsivity (Urgency, Premeditation (lack of), Preservation (lack of), Sensation Seeking, Positive Urgency Impulsive Behavior Scale – Negative Urgency subscale (UPPS-P)), SI (Beck Suicide Scale (BSS), Columbia Suicide Severity Rating Scale (C-SSRS)), PTSD symptoms (PTSD Checklist for DSM-5 (CAPS-5) (PCL-5)), and depressive symptoms (Patient Health Questionnaire-9 (PHQ-9), Inventory for Depressive Symptoms – Self-Report (IDSSR)). We will collect qualitative data through semi-structured interviews to elicit feedback on the subject’s experience and symptoms. RESULTS This study protocol was approved by the Edward Hines Jr Veterans Administration Hospital Institutional Review Board (Hines IRB#14-003) and registered on ClinicalTrials.gov (NCT05647044). This novel treatment is a 5-year research project (04/01/2023 – 03/31/2028) funded by the VA Rehabilitation Research & Development (RR&D) service (CDA2 grant IK2 RX002938). Study results will be disseminated at or before the project’s end date in March 2028. CONCLUSIONS We will provide preliminary evidence of the safety, feasibility, and acceptability of a novel frontal pole iTBS treatment for mTBI, impulsivity, SI/SA, and functional deficits. CLINICALTRIAL ClinicalTrials.gov (NCT05647044); https://clinicaltrials.gov/study/NCT05647044

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“…The mechanism of relief is attributed to stronger resting state connectivity [162]. Similarly, Veterans with depression (n = 321), or depression and hmTBI (n = 337), showed relief from depression after 30-rTMS sessions [166]. Their interpretation was that hmTBI did not interfere with the benefit of rTMS for depression, but neither did rTMS provide additional benefit.…”

Section: Rtms and Tdcs Benefits In Humans After Tbimentioning

confidence: 99%

The Rehabilitation Potential of Neurostimulation for Mild Traumatic Brain Injury in Animal and Human Studies

McNerney,

Gurkoff,

Beard

et al. 2023

Brain Sciences

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Neurostimulation carries high therapeutic potential, accompanied by an excellent safety profile. In this review, we argue that an arena in which these tools could provide breakthrough benefits is traumatic brain injury (TBI). TBI is a major health problem worldwide, with the majority of cases identified as mild TBI (mTBI). MTBI is of concern because it is a modifiable risk factor for dementia. A major challenge in studying mTBI is its inherent heterogeneity across a large feature space (e.g., etiology, age of injury, sex, treatment, initial health status, etc.). Parallel lines of research in human and rodent mTBI can be collated to take advantage of the full suite of neuroscience tools, from neuroimaging (electroencephalography: EEG; functional magnetic resonance imaging: fMRI; diffusion tensor imaging: DTI) to biochemical assays. Despite these attractive components and the need for effective treatments, there are at least two major challenges to implementation. First, there is insufficient understanding of how neurostimulation alters neural mechanisms. Second, there is insufficient understanding of how mTBI alters neural function. The goal of this review is to assemble interrelated but disparate areas of research to identify important gaps in knowledge impeding the implementation of neurostimulation.

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Repetitive Transcranial Magnetic Stimulation for Depression and Posttraumatic Stress Disorder in Veterans With Mild Traumatic Brain Injury

Cited by 11 publications

References 35 publications

Interleaved TMS/fMRI shows that threat decreases dlPFC-mediated top-down regulation of emotion processing

Interleaved TMS/fMRI shows that threat decreases dlPFC-mediated top-down regulation of emotion processing

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 (Preprint)

The Rehabilitation Potential of Neurostimulation for Mild Traumatic Brain Injury in Animal and Human Studies

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