Social Determinant of Unconventional Resilience Tactical Engagement with Bonding Patterns.

Building upon our strategic framework and operational model, we will discuss findings from our ethnographic study, entitled: "The Impact of Catastrophic Injury Exposure on Resilience in Special Operations Surgical Teams (SOSTs)," to explain the tactical nature and importance of social determinants within our new characterization of unconventional resilience. Our fourth paper in this series, will explain how bonding patterns establish the quality of intra- and interpersonal connections that create a tensive conduit for the pressure of performance within our operational model, allowing for dynamic freedom of maneuver to take place in ambiguity. We will use qualita- tive quotes to illustrate various ways SOST medics relate to themselves, other people, and the Special Operations Forces (SOF) culture. To achieve our goals, we will: 1) provide an in- troduction to social determinants as tactical engagement with unconventional resilience; 2) define the social determinant of bonding patterns as extrapolated from qualitative data as well as use qualitative data to thematize various types of bonding patterns; and 3) relate tactical engagement with bonding pat- terns to our metaphor of bag sets. We conclude by gesturing to the importance of bonding patterns in orienting SOF medics' proprioception and kinesthesia in the SOF performance space.

Longitudinal examination of borderline personality disorder symptoms and drug use: The influence of negative and positive emotion dysregulation.

Borderline personality disorder (BPD) is associated with greater substance use. Emotion dysregulation has been implicated in both BPD and substance use, yet there is limited research examining the role of emotion dysregulation in the BPD-substance use relation. We examined the independent and interactive associations of BPD symptoms and emotion dysregulation in reported drug use over 1 year. Participants (N = 143) were over-recruited for BPD, assessed via interview, and completed measures of negative and positive emotion dysregulation. Drug use frequency was assessed with monthly surveys over a 1-year period. Results demonstrated interrelations among BPD symptoms and both negative and positive emotion dysregulation. However, when modeling BPD and emotion dysregulation together, only higher BPD symptoms were associated with more frequent drug use. Findings support the relation of BPD symptoms and emotion dysregulation but suggest that emotion dysregulation may not account for drug use frequency above and beyond BPD in community-recruited populations.

Who tests for lead and why? A 10-year analysis of blood lead screening, follow-up and CNS outcomes in a statewide US healthcare system.

OBJECTIVES: This study aims to determine (1) which providers in US healthcare systems order lead tests, why and at what frequency and (2) whether current patient population lead levels are predictive of clinical outcomes. METHODS: Retrospective medical record study of all blood lead tests in the Medical University of South Carolina healthcare system 2012-2016 and consequent evidence of central nervous system (CNS)-related disease across a potential 10-year window (2012-2022). RESULTS: Across 4 years, 9726 lead tests resulted for 7181 patients (49.0% female; 0-94 years), representing 0.2% of the hospital population. Most tests were for young (76.6%≤age 3) and non-Hispanic black (47.2%) and Hispanic (26.7%) patients. A wide variety of providers ordered tests; however, most were ordered by paediatrics, psychiatry, internal medicine and neurology. Lead levels ranged from ≤2.0 µg/dL (80.8%) to ≥10 µg/dL (0.8%; max 36 µg/dL). 201 children (3.1%) had initial lead levels over the reference value for case management at the time (5.0 µg/dL). Many high level children did not receive follow-up testing in the system (36.3%) and those that did often failed to see levels fall below 5.0 µg/dL (80.1%). Non-Hispanic black and Hispanic patients were more likely to see lead levels stay high or go up over time. Over follow-up, children with high lead levels were more likely to receive new attention-deficit/hyperactivity disorder and conduct disorder diagnoses and new psychiatric medications. No significant associations were found between lead test results and new CNS diagnoses or medications among adults. CONCLUSIONS: Hospital lead testing covers a small portion of patients but includes a wide range of ages, presentations and provider specialities. Lack of lead decline among many paediatric patients suggests there is room to improve provider guidance around when to test and follow-up.

Social Determinant of Unconventional Resilience: Tactical Engagement with Impression Management.

Building upon our operational model, we will discuss findings from our ethnographic study titled "The Impact of Catastrophic Injury Exposure on Resilience in Special Operations Surgical Teams" to establish that impression management allows Special Operation Forces (SOF) medics to navigate implicit social status symbols to either degrade or optimize performance. We will use qualitative quotes to explore how Special Operations Surgical Team (SOST) medics engage in impression management to establish individual, team, and/or organizational competency to deal with ambiguity. To achieve our goals, we will: 1) provide a background on impression management and perception of competency; 2) define the social determinant of impression management extrapolated from qualitative data as well as use qualitative data to thematize various types of impression management; and 3) relate tactical engagement with impression to our metaphor of bag sets. We conclude by gesturing to the importance of impression management in orienting SOF medics' proprioception and kinesthesia in the SOF performance space.

EEG synchronized left prefrontal transcranial magnetic stimulation (TMS) for treatment resistant depression is feasible and produces an entrainment dependent clinical response: A randomized controlled double blind clinical trial.

BACKGROUND: Synchronizing a TMS pulse with a person's underlying EEG rhythm can modify the brain's response. It is unclear if synchronizing rTMS trains might boost the antidepressant effect of TMS. In this first-in-human trial, we demonstrated that a single TMS pulse over the prefrontal cortex produces larger effects in the anterior cingulate depending on when it is fired relative to the individual's EEG alpha phase. OBJECTIVE/HYPOTHESES: We had three hypotheses. 1) It is feasible to synchronize repetitive TMS (rTMS) delivery to a person's preferred prefrontal alpha phase in each train of every session during a 30-visit TMS depression treatment course. 2) EEG-synchronized rTMS would produce progressive entrainment greater than unsynchronized (UNSYNC) rTMS. And 3) SYNC TMS would have better antidepressant effects than UNSYNC (remission, final Hamilton Depression Rating <10). METHODS: We enrolled (n = 34) and treated (n = 28) adults with treatment resistant depression (TRD) and randomized them to receive six weeks (30 treatments) of left prefrontal rTMS at their individual alpha frequency (IAF) (range 6-13 Hz). Prior to starting the clinical trial, all patients had an interleaved fMRI-EEG-TMS (fET) scan to determine which phase of their alpha rhythm would produce the largest BOLD response in their dorsal anterior cingulate. Our clinical EEG-rTMS system then delivered the first TMS pulse in each train time-locked to this patient-specific 'preferred phase' of each patient's left prefrontal alpha oscillation. We randomized patients (1:1) to SYNC or UNSYNC, and all were treated at their IAF. Only the SYNC patients had the first pulse of each train for all sessions synchronized to their individualized preferred alpha phase (75 trains/session ×30 sessions, 2250 synchronizations per patient over six weeks). The UNSYNC group used a random firing with respect to the alpha wave. All other TMS parameters were balanced between the two groups. The system interfaced with a MagStim Horizon air-cooled Fig. 8 TMS coil. All patients were treated at their IAF, coil in the F3 position, 120 % MT, frequency 6-13 Hz, 40 pulses per train, average 15-s inter-train interval, 3000 pulses per session. All patients, raters, and treaters were blinded. RESULTS: In the intent to treat (ITT) sample, both groups had significant clinical improvement from baseline with no significant between-group differences, with the USYNC group having mathematically more remitters but fewer responders. (ITT -15 SYNC; 13 UNSYNC, response 5 (33 %), 1 (7 %), remission 2 (13 %), 6 (46 %). The same was true with the completer sample - 12 SYNC; 12 UNSYNC, response 4, 4 (both 30 %), remission 2 (17 %), 3 (25 %)). The clinical EEG phase synchronization system performed well with no failures. The average treatment session was approximately 90 min, with 30 min for placing the EEG cap and the actual TMS treatment for 45 min (which included gathering 10 min of resting EEG). Four subjects (1 SYNC) withdrew before six weeks of treatment. All 24 completer patients were treated for six weeks despite the trial occurring during the COVID pandemic. SYNC patients exhibited increased post-stimulation EEG entrainment over the six weeks. A detailed secondary analysis of entrainment data in the SYNC group showed that responders and non-responders in this group could be cleanly separated based on the total number of sessions with entrainment and the session-to-session precision of the entrained phase. For the SYNC group only, depression improvement was greater when more sessions were entrained at similar phases. CONCLUSIONS: Synchronizing prefrontal TMS with a patient's prefrontal alpha frequency in a blinded clinical trial is possible and produces progressive EEG entrainment in synchronized patients only. There was no difference in overall clinical response in this small clinical trial. A secondary analysis showed that the consistency of the entrained phase across sessions was significantly associated with response outcome only in the SYNC group. These effects may not simply be due to how the stimulation is delivered but also whether the patient's brain can reliably entrain to a precise phase. EEG-synchronized clinical delivery of TMS is feasible and requires further study to determine the best method for determining the phase for synchronization.

Biomarkers predict the efficacy of closed-loop rTMS treatment for refractory depression.

Transcranial magnetic stimulation (TMS) is a non-invasive FDA-approved therapy for major depressive disorder (MDD), specifically for treatment-resistant depression (TRD). Though offering promise for those with TRD, its effectiveness is less than one in two patients (i.e., less than 50%). Limits on efficacy may be due to individual patient variability, but to date, there are no established biomarkers or measures of target engagement that can predict efficacy. Additionally, TMS efficacy is typically not assessed until a six-week treatment ends, precluding interim re-evaluations of the treatment. Here, we report results using a closed-loop phase-locked repetitive TMS (rTMS) treatment that synchronizes the delivery of rTMS based on the timing of the pulses relative to a patient's individual electroencephalographic (EEG) prefrontal alpha oscillation indexed by functional magnetic resonance imaging (fMRI). Among responders, synchronized rTMS produces two systematic changes in brain dynamics: a reduction in global cortical excitability and enhanced phase entrainment of cortical dynamics. These effects predict clinical outcomes in the synchronized treatment group but not in an active-treatment unsynchronized control group. The systematic decrease in excitability and increase in entrainment correlated with treatment efficacy at the endpoint and intermediate weeks during the synchronized treatment. Specifically, we show that weekly biomarker tracking enables efficacy prediction and dynamic adjustments through a treatment course, improving the overall response rates. This innovative approach advances the prospects of individualized medicine in MDD and holds potential for application in other neuropsychiatric disorders.

Clinical Inquiry in Nursing Readiness Fellowship: Increasing Air Force Nurse Corps Evidence-Based Practice Leadership Infrastructure.

BACKGROUND: Increasing demands to generate, translate, and implement evidence into practice in manpower and budget-constrained environments triggered innovative support for the nursing scientific community. The Clinical Inquiry in Nursing Readiness (CINR) fellowship is a solution to integrate readiness into clinical inquiry priorities and develop future experts in the field. METHODS: This article describes the fellowship program structure, implementation, and contributions to nursing science, readiness, and professional development. We share specific recommendations based on our experiences to enhance and sustain this valuable fellowship program. RESULTS: Six fellows have completed the CINR fellowship since its launch in July 2019. Fellows garnered $40,000 in grant funds for five evidence-based practices, two research studies, and six clinical inquiry initiatives. So far, the fellows have produced 20 knowledge products: Three published manuscripts, three evidence-based resource toolkits, nine professional conference presentations (one international), five professional certifications, a variety of organization-wide leadership briefings, and two military decorations specific to the pandemic response. CONCLUSIONS: Establishing a fellowship program to develop a pipeline of readiness-focused nurse scientists and evidence-based practice experts builds future capacity for the enterprise while professionally developing individual nurses for advanced degrees and clinical inquiry leadership roles. Individuals and organizations aspiring to promote a culture of nursing inquiry may benefit from fellowships such as the CINR program.

Early Enteral Nutrition in Aeromedically Evacuated Critically Ill/Injured Patients With a Resultant Validation Algorithm for the Theater Validating Flight Surgeon.

INTRODUCTION: Early enteral feeding in critically ill/injured patients promotes gut integrity and immunocompetence and reduces infections and intensive care unit/hospital stays. Aeromedical evacuation (AE) often takes place concurrently. As a result, AE and early enteral feeding should be inseparable. MATERIALS AND METHODS: This retrospective descriptive study employed AE enteral nutrition (EN) data (2007-2019) collected from patients who were U.S. citizens and mechanically ventilated. The dataset was created from the En Route Critical Care, Transportation Command Regulating and Command and Control Evacuation System, and Theater Medical Data Store databases. Comparisons were performed between patients extracted and patients not extracted, patients treated with EN and patients treated without EN, and within the EN group, between AE Fed and AE Withheld. The impact of the nutrition support in the Joint Trauma System Clinical Practice Guidelines (CPG) was assessed using the 'before' and 'after' methodology. RESULTS: An uptick in feeding rates was found after the 2010 CPG, 15% → 17%. With the next two CPG iterations, rates rose significantly, 17% → 48%. Concurrently, AE feeding holds rose significantly, 10% → 24%, later dropping to 17%. In addition, little difference was found between those patients not enterally fed preflight and those enterally fed across collected demographic, mission, and clinical parameters. Likewise, no difference was found between those enterally fed during AE and those withheld. Yet, 83% of the study's patients were not fed, and 18% of those that were fed had feeding withheld for AE. CONCLUSIONS: It appeared that the Clinical Practice Guidelines (CPGs) reinforced the value of feeding, but may well have sensitized to the threat of aspiration. It also appeared that early enteral feeding was underprescribed and AE feeding withholds were overprescribed. Consequently, an algorithm was devised for the Theater Validating Flight Surgeon, bearing in mind relevant preflight/inflight/clinical issues, with prescriptions designed to boost feeding, diminish AE withholding, and minimize complications.

Unconventional Resilience: An Operational Model.

This is the third of nine planned papers drawn from the findings of our ethnographic study entitled "The Impact of Catastrophic Injury Exposure on Resilience in Special Operations Surgical Teams." Building from our strategic framework, this paper will establish that resilience is better understood as cohesive adaptation within a Special Operation Forces (SOF) cultural ecosystem. Exploring unconventional resilience as the inter-relationship across the organization, team, and individual, we will use qualitative quotes to describe the ecosystem of dynamic freedom of maneuver in ambiguity. To achieve our goals, we will: 1) compare conventional and unconventional resilience to operationalize the components of our strategic framework; 2) use qualitative quotes to show how the ecosystem of unconventional resilience functions at each level supporting our operational model; and 3) describe how the operational model of unconventional resilience links to tactical performance through five social determinants. We conclude by gesturing to how transformational change-agency applies to practical performance of all SOF medics.

Increased entrainment and decreased excitability predict efficacious treatment of closed-loop phase-locked rTMS for treatment-resistant depression.

Transcranial magnetic stimulation (TMS) is an FDA-approved therapy for major depressive disorder (MDD), specifically for patients who have treatment-resistant depression (TRD). However, TMS produces response or remission in about 50% of patients but is ineffective for the other 50%. Limits on efficacy may be due to individual patient variability, but to date, there are no good biomarkers or measures of target engagement. In addition, TMS efficacy is typically not assessed until a six-week treatment ends, precluding the evaluation of intermediate improvements during the treatment duration. Here, we report on results using a closed-loop phase-locked repetitive TMS (rTMS) treatment that synchronizes the delivery of rTMS based on the timing of the pulses relative to a patient's individual electroencephalographic (EEG) prefrontal alpha oscillation informed by functional magnetic resonance imaging (fMRI). We find that, in responders, synchronized delivery of rTMS produces two systematic changes in brain dynamics. The first change is a decrease in global cortical excitability, and the second is an increase in the phase entrainment of cortical dynamics. These two effects predict clinical outcomes in the synchronized treatment group but not in an active-treatment unsynchronized control group. The systematic decrease in excitability and increase in entrainment correlated with treatment efficacy at the endpoint and intermediate weeks during the synchronized treatment. Specifically, we show that weekly tracking of these biomarkers allows for efficacy prediction and potential of dynamic adjustments through a treatment course, improving the overall response rates.

Higher Dose Noninvasive Transcutaneous Auricular Vagus Nerve Stimulation Increases Feeding Volumes and White Matter Microstructural Complexity in Open-Label Study of Infants Slated for Gastrostomy Tube.

OBJECTIVE: To determine whether transcutaneous auricular vagus nerve stimulation (taVNS) paired with twice daily bottle feeding increases the volume of oral feeds and white matter neuroplasticity in term-age-equivalent infants failing oral feeds and determined to need a gastrostomy tube. STUDY DESIGN: In this prospective, open-label study, 21 infants received taVNS paired with 2 bottle feeds for 2 - 3 weeks (2x). We compared 1) increase oral feeding volumes with 2x taVNS and previously reported once daily taVNS (1x) to determine a dose response, 2) number of infants who attained full oral feeding volumes, and 3) diffusional kurtosis imaging and magnetic resonance spectroscopy before and after treatment by paired t tests. RESULTS: All 2x taVNS treated infants significantly increased their feeding volumes compared with 10 days before treatment. Over 50% of 2x taVNS infants achieved full oral feeds but in a shorter time than 1x cohort (median 7 days [2x], 12.5 days [1x], P < .05). Infants attaining full oral feeds showed greater increase in radial kurtosis in the right corticospinal tract at the cerebellar peduncle and external capsule. Notably, 75% of infants of diabetic mothers failed full oral feeds, and their glutathione concentrations in the basal ganglia, a measure of central nervous system oxidative stress, were significantly associated with feeding outcome. CONCLUSIONS: In infants with feeding difficulty, increasing the number of daily taVNS-paired feeding sessions to twice-daily significantly accelerates response time but not the overall response rate of treatment. taVNS was associated with white matter motor tract plasticity in infants able to attain full oral feeds. TRIAL REGISTRATION: Clinicaltrials.gov (NCT04643808).

Unconventional Resilience: A Strategic Framework.

This will be the second in a series of nine articles in which we discuss findings from our ethnographic study entitled "The Impact of Catastrophic Injury Exposure on Resilience in Special Operations Surgical Teams." Our goal in this article is to establish the practical importance of redefining resilience within a strategic framework. Our bottom-up approach to strategy development explores unconventional resilience as an integrated transformational process that promotes change-agency through the force of movement. Synthesis of empirical data derived from participant interviews and focus groups highlights conceptual attributes that make up the essential components of this framework. To achieve our goal, the authors (1) briefly remind readers how we have problematized conventional resilience; (2) explain how we analyzed qualitative quotes to extrapolate our definition of unconventional resilience; and (3) describe in detail our strategic framework. We conclude by gesturing to why this strategic framework is applicable to practical performance of all Special Operation Forces (SOF) medics.

Conventional Resilience and the Impact of Catastrophic Injury Exposure on Special Operations Surgical Teams.

This article presents a justification for using an ethnographic approach to research resilience. Our hypothesis is that the conventional resilience construct is ineffective in achieving its stated goal of mitigating diagnosable stress pathologies because it is grounded in a set of assumptions that overlook human experience when examining human performance in combat. To achieve this goal, we (1) describe the evolution of the strategic framework within which the conventional resilience construct is defined; (2) highlight certain limiting assumptions entailed in this framework; (3) explain how bottom-up ethnographic research relates the medic's practical performance to military requirements and mission capabilities; and (4) articulate the unique elements of our study that widen the aperture of the conventional resilience construct. We conclude by gesturing to initial research findings.

The timing of transcranial magnetic stimulation relative to the phase of prefrontal alpha EEG modulates downstream target engagement.

BACKGROUND: The communication through coherence model posits that brain rhythms are synchronized across different frequency bands and that effective connectivity strength between interacting regions depends on their phase relation. Evidence to support the model comes mostly from electrophysiological recordings in animals while evidence from human data is limited. METHODS: Here, an fMRI-EEG-TMS (fET) instrument capable of acquiring simultaneous fMRI and EEG during noninvasive single pulse TMS applied to dorsolateral prefrontal cortex (DLPFC) was used to test whether prefrontal EEG alpha phase moderates TMS-evoked top-down influences on subgenual, rostral and dorsal anterior cingulate cortex (ACC). Six runs (276 total trials) were acquired in each participant. Phase at each TMS pulse was determined post-hoc using single-trial sorting. Results were examined in two independent datasets: healthy volunteers (HV) (n = 11) and patients with major depressive disorder (MDD) (n = 17) collected as part of an ongoing clinical trial. RESULTS: In both groups, TMS-evoked functional connectivity between DLPFC and subgenual ACC (sgACC) depended on the EEG alpha phase. TMS-evoked DLPFC to sgACC fMRI-derived effective connectivity (EC) was modulated by EEG alpha phase in healthy volunteers, but not in the MDD patients. Top-down EC was inhibitory for TMS pulses during the upward slope of the alpha wave relative to TMS timed to the downward slope of the alpha wave. Prefrontal EEG alpha phase dependent effects on TMS-evoked fMRI BOLD activation of the rostral anterior cingulate cortex were detected in the MDD patient group, but not in the healthy volunteer group. DISCUSSION: Results demonstrate that TMS-evoked top-down influences vary as a function of the prefrontal alpha rhythm, and suggest potential clinical applications whereby TMS is synchronized to the brain's internal rhythms in order to more efficiently engage deep therapeutic targets.

COVID-19 palliative care toolkit development and military health system deployment.

BACKGROUND: During the initial phase of the pandemic, we identified a critical gap in the Military Health System's access to palliative care. Our team of nurse scientists and evidence-based practice (EBP) facilitators aimed to develop and implement an evidence-based point of care palliative care toolkit for frontline workers in inpatient settings lacking established palliative care specialists. METHODOLOGY: We utilized Melnyk and Fineout-Overholt's (2018) seven-step EBP process. Six central themes were derived from 17 publications providing an evidence-base for toolkit resource selection and development. Our practice change implementation was piloted at a large West Coast military treatment facility. We included iPads in the toolkit for patient communication and palliative mobile application use. RESULTS: The most significant finding was the critical and continued need for basic palliative care education and training. Integrating the palliative care toolkit into daily practice was promising yet challenging due to the high volume of deployed medical staff.

A pilot randomized controlled trial of supervised, at-home, self-administered transcutaneous auricular vagus nerve stimulation (taVNS) to manage long COVID symptoms.

BACKGROUND: Although the coronavirus disease 19 (COVID-19) pandemic has now impacted the world for over two years, the persistent secondary neuropsychiatric effects are still not fully understood. These "long COVID" symptoms, also referred to as post-acute sequelae of SARS-CoV-2 infection (PASC), can persist for months after infection without any effective treatments. Long COVID involves a complex heterogenous symptomology and can lead to disability and limit work. Long COVID symptoms may be due to sustained inflammatory responses and prolonged immune response after infection. Interestingly, vagus nerve stimulation (VNS) may have anti-inflammatory effects, however, until recently, VNS could not be self-administered, at-home, noninvasively. METHODS: We created a double-blind, noninvasive transcutaneous auricular VNS (taVNS) system that can be self-administered at home with simultaneous remote monitoring of physiological biomarkers and video supervision by study staff. Subsequently, we carried out a pilot (n = 13) randomized, sham-controlled, trial with this system for four weeks to treat nine predefined long covid symptoms (anxiety, depression, vertigo, anosmia, ageusia, headaches, fatigue, irritability, brain fog). No in-person patient contact was needed, with informed consent, trainings, ratings, and all procedures being conducted remotely during the pandemic (2020-2021) and equipment being shipped to individuals' homes. This trial was registered on ClinicalTrials.gov under the identifier: NCT04638673 registered November 20, 2020. RESULTS: Four-weeks of at-home self-administered taVNS (two, one-hour sessions daily, delivered at suprathreshold intensities) was feasible and safe. Although our trial was not powered to determine efficacy as an intervention in a heterogenous population, the trends in the data suggest taVNS may have a mild to moderate effect in reducing mental fatigue symptoms in a subset of individuals. CONCLUSIONS: This innovative study demonstrates the safety and feasibility of supervised self-administered taVNS under a fully contactless protocol and suggests that future studies can safely investigate this novel form of brain stimulation at-home for a variety of neuropsychiatric and motor recovery applications.

A pilot randomized controlled trial of supervised, at-home, self-administered transcutaneous auricular vagus nerve stimulation (taVNS) to manage long COVID symptoms.

Background Although the coronavirus disease 19 (COVID-19) pandemic has now impacted the world for over two years, the persistent secondary neuropsychiatric effects are still not fully understood. These "long COVID" symptoms, also referred to as post-acute sequelae of SARS-CoV-2 infection (PASC), can persist for months after infection without any effective treatments. Long COVID involves a complex heterogenous symptomology and can lead to disability and limit work. Long COVID symptoms may be due to sustained inflammatory responses and prolonged immune response after infection. Interestingly, vagus nerve stimulation (VNS) may have anti-inflammatory effects, however, until recently, VNS could not be self-administered, at-home, noninvasively. Methods We created a double-blind, noninvasive transcutaneous auricular VNS (taVNS) system that can be self-administered at home with simultaneous remote monitoring of physiological biomarkers and video supervision by study staff. Subsequently, we carried out a pilot (n = 13) randomized, sham-controlled, trial with this system for four weeks to treat nine predefined long covid symptoms (anxiety, depression, vertigo, anosmia, ageusia, headaches, fatigue, irritability, brain fog). No in-person patient contact was needed, with informed consent, trainings, ratings, and all procedures being conducted remotely during the pandemic (2020-2021) and equipment being shipped to individuals' homes. This trial was registered onClinicalTrials.gov under the identifier: NCT04638673. Results Four-weeks of at-home self-administered taVNS (two, one-hour sessions daily, delivered at suprathreshold intensities) was feasible and safe. Although our trial was not powered to determine efficacy as an intervention in a heterogenous population, the trends in the data suggest taVNS may have a mild to moderate effect in reducing mental fatigue symptoms in a subset of individuals. This innovative study demonstrates the safety and feasibility of supervised self-administered taVNS under a fully contactless protocol and suggests that future studies can safely investigate this novel form of brain stimulation at-home for a variety of neuropsychiatric and motor recovery applications.

Electrical stimulation of the trigeminal nerve improves olfaction in healthy individuals: A randomized, double-blind, sham-controlled trial.

BACKGROUND: Both activated by environmental odorants, there is a clear role for the intranasal trigeminal and olfactory nerves in smell function. Unfortunately, our ability to perceive odorants decreases with age or with injury, and limited interventions are available to treat smell loss. OBJECTIVE: We investigated whether electrical stimulation of the trigeminal nerve via trigeminal nerve stimulation (TNS) or transcranial direct current stimulation (tDCS) modulates odor sensitivity in healthy individuals. METHODS: We recruited 20 healthy adults (12 Female, mean age = 27) to participate in this three-visit, randomized, double-blind, sham-controlled trial. Participants were randomized to receive one of three stimulation modalities (TNS, tDCS, or sham) during each of their visits. Odor detection thresholds were obtained at baseline, immediately post-intervention, and 30-min post-intervention. Furthermore, participants were asked to complete a sustained attention task and mood assessments before odor detection testing. RESULTS: Findings reveal a timeXcondition interaction for guaiacol (GUA) odorant detection thresholds (F (3.188, 60.57) = 3.833, P = 0.0125), but not phenyl ethyl alcohol (PEA) odorant thresholds. At 30-min post-stimulation, both active TNS and active tDCS showed significantly increased sensitivity to GUA compared to sham TNS (Sham TNS = -8.30% vs. Active TNS = 9.11%, mean difference 17.43%, 95% CI 5.674 to 29.18, p = 0.0044; Sham TNS = -8.30% vs. Active tDCS = 13.58%, mean difference 21.89%, 95% CI 10.47 to 33.32, p = 0.0004). CONCLUSION: TNS is a safe, simple, noninvasive method for boosting olfaction. Future studies should investigate the use of TNS on smell function across different stimulation parameters, odorants, and patient populations.

Daily prefrontal closed-loop repetitive transcranial magnetic stimulation (rTMS) produces progressive EEG quasi-alpha phase entrainment in depressed adults.

BACKGROUND: Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation modality that can treat depression, obsessive-compulsive disorder, or help smoking cessation. Research suggests that timing the delivery of TMS relative to an endogenous brain state may affect efficacy and short-term brain dynamics. OBJECTIVE: To investigate whether, for a multi-week daily treatment of repetitive TMS (rTMS), there is an effect on brain dynamics that depends on the timing of the TMS relative to individuals' prefrontal EEG quasi-alpha rhythm (between 6 and 13 Hz). METHOD: We developed a novel closed-loop system that delivers personalized EEG-triggered rTMS to patients undergoing treatment for major depressive disorder. In a double blind study, patients received daily treatments of rTMS over a period of six weeks and were randomly assigned to either a synchronized or unsynchronized treatment group, where synchronization of rTMS was to their prefrontal EEG quasi-alpha rhythm. RESULTS: When rTMS is applied over the dorsal lateral prefrontal cortex (DLPFC) and synchronized to the patient's prefrontal quasi-alpha rhythm, patients develop strong phase entrainment over a period of weeks, both over the stimulation site as well as in a subset of areas distal to the stimulation site. In addition, at the end of the course of treatment, this group's entrainment phase shifts to be closer to the phase that optimally engages the distal target, namely the anterior cingulate cortex (ACC). These entrainment effects are not observed in the group that is given rTMS without initial EEG synchronization of each TMS train. CONCLUSIONS: The entrainment effects build over the course of days/weeks, suggesting that these effects engage neuroplastic changes which may have clinical consequences in depression or other diseases.