Epidural electrical stimulation of the cervical spinal cord opposes opioid-induced respiratory depression.

Opioid overdose suppresses brainstem respiratory circuits, causes apnoea and may result in death. Epidural electrical stimulation (EES) at the cervical spinal cord facilitated motor activity in rodents and humans, and we hypothesized that EES of the cervical spinal cord could antagonize opioid-induced respiratory depression in humans. Eighteen patients requiring surgical access to the dorsal surface of the spinal cord between C2 and C7 received EES or sham stimulation for up to 90 s at 5 or 30 Hz during complete (OFF-State) or partial suppression (ON-State) of respiration induced by remifentanil. During the ON-State, 30 Hz EES at C4 and 5 Hz EES at C3/4 increased tidal volume and decreased the end-tidal carbon dioxide level compared to pre-stimulation control levels. EES of 5 Hz at C5 and C7 increased respiratory frequency compared to pre-stimulation control levels. In the OFF-State, 30 Hz cervical EES at C3/4 terminated apnoea and induced rhythmic breathing. In cadaveric tissue obtained from a brain bank, more neurons expressed both the neurokinin 1 receptor (NK1R) and somatostatin (SST) in the cervical spinal levels responsive to EES (C3/4, C6 and C7) compared to a region non-responsive to EES (C2). Thus, the capacity of cervical EES to oppose opioid depression of respiration may be mediated by NK1R+/SST+ neurons in the dorsal cervical spinal cord. This study provides proof of principle that cervical EES may provide a novel therapeutic approach to augment respiratory activity when the neural function of the central respiratory circuits is compromised by opioids or other pathological conditions. KEY POINTS: Epidural electrical stimulation (EES) using an implanted spinal cord stimulator (SCS) is an FDA-approved method to manage chronic pain. We tested the hypothesis that cervical EES facilitates respiration during administration of opioids in 18 human subjects who were treated with low-dose remifentanil that suppressed respiration (ON-State) or high-dose remifentanil that completely inhibited breathing (OFF-State) during the course of cervical surgery. Dorsal cervical EES of the spinal cord augmented the respiratory tidal volume or increased the respiratory frequency, and the response to EES varied as a function of the stimulation frequency (5 or 30 Hz) and the cervical level stimulated (C2-C7). Short, continuous cervical EES restored a cyclic breathing pattern (eupnoea) in the OFF-State, suggesting that cervical EES reversed the opioid-induced respiratory depression. These findings add to our understanding of respiratory pattern modulation and suggest a novel mechanism to oppose the respiratory depression caused by opioids.

Sacroperineal Reconstruction With Inferior Gluteal Artery Perforator Flaps After Resection of Locally Advanced Primary and Recurrent Anorectal Malignancy.

ABSTRACT: Modern interdisciplinary concepts with involvement of various surgical specialties can considerably reduce perioperative morbidity after sacroperineal resection of locally advanced primary or recurrent anorectal malignancies. Resultant defects can represent a major challenge for reconstruction particularly with chemoradiotherapy. The aim is to assess the long-term outcomes of sacroperineal reconstruction using inferior gluteal artery perforator flaps.We performed a retrospective data analysis on 31 patients who were treated with inferior gluteal artery perforator flaps (n = 61) over the period 2009-2021. The demographic data, comorbidities, operative details, and outcomes with special focus on wound infection and dehiscence were recorded.The median age was 42 year (range, 25-82 years) with preponderance of males (n = 21). The follow-up period ranged from 6 to 80 months. Early minor complications included superficial wound dehiscence (3), which was managed conservatively, whereas the major (2) included deep wound collection and infection (1), which required surgical drainage, and perineal hernia, which required repair. All flaps survived completely.Inferior gluteal artery perforator flaps are safe, robust, and reliable with less donor side morbidity and positive impact on quality of life. It should be considered as a valuable tool in the reconstructive armamentarium of sacroperineal defects within a multidisciplinary setting.

Early brain biomarkers of post-traumatic seizures: initial report of the multicentre epilepsy bioinformatics study for antiepileptogenic therapy (EpiBioS4Rx) prospective study.

BACKGROUND: Traumatic brain injury (TBI) causes early seizures and is the leading cause of post-traumatic epilepsy. We prospectively assessed structural imaging biomarkers differentiating patients who develop seizures secondary to TBI from patients who do not. DESIGN: Multicentre prospective cohort study starting in 2018. Imaging data are acquired around day 14 post-injury, detection of seizure events occurred early (within 1 week) and late (up to 90 days post-TBI). RESULTS: From a sample of 96 patients surviving moderate-to-severe TBI, we performed shape analysis of local volume deficits in subcortical areas (analysable sample: 57 patients; 35 no seizure, 14 early, 8 late) and cortical ribbon thinning (analysable sample: 46 patients; 29 no seizure, 10 early, 7 late). Right hippocampal volume deficit and inferior temporal cortex thinning demonstrated a significant effect across groups. Additionally, the degree of left frontal and temporal pole thinning, and clinical score at the time of the MRI, could differentiate patients experiencing early seizures from patients not experiencing them with 89% accuracy. CONCLUSIONS AND RELEVANCE: Although this is an initial report, these data show that specific areas of localised volume deficit, as visible on routine imaging data, are associated with the emergence of seizures after TBI.

Traumatic axonal injury influences the cognitive effect of non-invasive brain stimulation.

Non-invasive brain stimulation has been widely investigated as a potential treatment for a range of neurological and psychiatric conditions, including brain injury. However, the behavioural effects of brain stimulation are variable, for reasons that are poorly understood. This is a particular challenge for traumatic brain injury, where patterns of damage and their clinical effects are heterogeneous. Here we test the hypothesis that the response to transcranial direct current stimulation following traumatic brain injury is dependent on white matter damage within the stimulated network. We used a novel simultaneous stimulation-MRI protocol applying anodal, cathodal and sham stimulation to 24 healthy control subjects and 35 patients with moderate/severe traumatic brain injury. Stimulation was applied to the right inferior frontal gyrus/anterior insula node of the salience network, which was targeted because our previous work had shown its importance to executive function. Stimulation was applied during performance of the Stop Signal Task, which assesses response inhibition, a key component of executive function. Structural MRI was used to assess the extent of brain injury, including diffusion MRI assessment of post-traumatic axonal injury. Functional MRI, which was simultaneously acquired to delivery of stimulation, assessed the effects of stimulation on cognitive network function. Anodal stimulation improved response inhibition in control participants, an effect that was not observed in the patient group. The extent of traumatic axonal injury within the salience network strongly influenced the behavioural response to stimulation. Increasing damage to the tract connecting the stimulated right inferior frontal gyrus/anterior insula to the rest of the salience network was associated with reduced beneficial effects of stimulation. In addition, anodal stimulation normalized default mode network activation in patients with poor response inhibition, suggesting that stimulation modulates communication between the networks involved in supporting cognitive control. These results demonstrate an important principle: that white matter structure of the connections within a stimulated brain network influences the behavioural response to stimulation. This suggests that a personalized approach to non-invasive brain stimulation is likely to be necessary, with structural integrity of the targeted brain networks an important criterion for patient selection and an individualized approach to the selection of stimulation parameters.

Cognitive enhancement with Salience Network electrical stimulation is influenced by network structural connectivity.

The Salience Network (SN) and its interactions are important for cognitive control. We have previously shown that structural damage to the SN is associated with abnormal functional connectivity between the SN and Default Mode Network (DMN), abnormal DMN deactivation, and impaired response inhibition, which is an important aspect of cognitive control. This suggests that stimulating the SN might enhance cognitive control. Here, we tested whether non-invasive transcranial direct current stimulation (TDCS) could be used to modulate activity within the SN and enhance cognitive control. TDCS was applied to the right inferior frontal gyrus/anterior insula cortex during performance of the Stop Signal Task (SST) and concurrent functional (f)MRI. Anodal TDCS improved response inhibition. Furthermore, stratification of participants based on SN structural connectivity showed that it was an important influence on both behavioural and physiological responses to anodal TDCS. Participants with high fractional anisotropy within the SN showed improved SST performance and increased activation of the SN with anodal TDCS, whilst those with low fractional anisotropy within the SN did not. Cathodal stimulation of the SN produced activation of the right caudate, an effect which was not modulated by SN structural connectivity. Our results show that stimulation targeted to the SN can improve response inhibition, supporting the causal influence of this network on cognitive control and confirming it as a target to produce cognitive enhancement. Our results also highlight the importance of structural connectivity as a modulator of network to TDCS, which should guide the design and interpretation of future stimulation studies.

Early seizures and temporal lobe trauma predict post-traumatic epilepsy: A longitudinal study.

OBJECTIVE: Injury severity after traumatic brain injury (TBI) is a well-established risk factor for the development of post-traumatic epilepsy (PTE). However, whether lesion location influences the susceptibility of seizures and development of PTE longitudinally has yet to be defined. We hypothesized that lesion location, specifically in the temporal lobe, would be associated with an increased incidence of both early seizures and PTE. As secondary analysis measures, we assessed the degree of brain atrophy and functional recovery, and performed a between-group analysis, comparing patients who developed PTE with those who did not develop PTE. METHODS: We assessed early seizure incidence (n = 90) and longitudinal development of PTE (n = 46) in a prospective convenience sample of patients with moderate-severe TBI. Acutely, patients were monitored with prospective cEEG and a high-resolution Magnetic Resonance Imaging (MRI) scan for lesion location classification. Chronically, patients underwent a high-resolution MRI, clinical assessment, and were longitudinally monitored for development of epilepsy for a minimum of 2 years post-injury. RESULTS: Early seizures, occurring within the first week post-injury, occurred in 26.7% of the patients (n = 90). Within the cohort of subjects who had evidence of early seizures (n = 24), 75% had a hemorrhagic temporal lobe injury on admission. For longitudinal analyses (n = 46), 45.7% of patients developed PTE within a minimum of 2 years post-injury. Within the cohort of subjects who developed PTE (n = 21), 85.7% had a hemorrhagic temporal lobe injury on admission and 38.1% had early (convulsive or non-convulsive) seizures on cEEG monitoring during their acute ICU stay. In a between-group analysis, patients with PTE (n = 21) were more likely than patients who did not develop PTE (n = 25) to have a hemorrhagic temporal lobe injury (p < 0.001), worse functional recovery (p = 0.003), and greater temporal lobe atrophy (p = 0.029). CONCLUSION: Our results indicate that in a cohort of patients with a moderate-severe TBI, 1) lesion location specificity (e.g. the temporal lobe) is related to both a high incidence of early seizures and longitudinal development of PTE, 2) early seizures, whether convulsive or non-convulsive in nature, are associated with an increased risk for PTE development, and 3) patients who develop PTE have greater chronic temporal lobe atrophy and worse functional outcomes, compared to those who do not develop PTE, despite matched injury severity characteristics. This study provides the foundation for a future prospective study focused on elucidating the mechanisms and risk factors for epileptogenesis.

The epilepsy bioinformatics study for anti-epileptogenic therapy (EpiBioS4Rx) clinical biomarker: Study design and protocol.

The Epilepsy Bioinformatics Study for Anti-epileptogenic Therapy (EpiBioS4Rx) is a longitudinal prospective observational study funded by the National Institute of Health (NIH) to discover and validate observational biomarkers of epileptogenesis after traumatic brain injury (TBI). A multidisciplinary approach has been incorporated to investigate acute electrical, neuroanatomical, and blood biomarkers after TBI that may predict the development of post-traumatic epilepsy (PTE). We plan to enroll 300 moderate-severe TBI patients with a frontal and/or temporal lobe hemorrhagic contusion. Acute evaluation with blood, imaging and electroencephalographic monitoring will be performed and then patients will be tracked for 2 years to determine the incidence of PTE. Validation of selected biomarkers that are discovered in planned animal models will be a principal feature of this work. Specific hypotheses regarding the discovery of biomarkers have been set forth in this study. An international cohort of 13 centers spanning 2 continents will be developed to facilitate this study, and for future interventional studies.

Improving transparency and scientific rigor in academic publishing.

Progress in basic and clinical research is slowed when researchers fail to provide a complete and accurate report of how a study was designed, executed, and the results analyzed. Publishing rigorous scientific research involves a full description of the methods, materials, procedures, and outcomes. Investigators may fail to provide a complete description of how their study was designed and executed because they may not know how to accurately report the information or the mechanisms are not in place to facilitate transparent reporting. Here, we provide an overview of how authors can write manuscripts in a transparent and thorough manner. We introduce a set of reporting criteria that can be used for publishing, including recommendations on reporting the experimental design and statistical approaches. We also discuss how to accurately visualize the results and provide recommendations for peer reviewers to enhance rigor and transparency. Incorporating transparency practices into research manuscripts will significantly improve the reproducibility of the results by independent laboratories.

Addition of Occupational Therapy to an Interdisciplinary Concussion Clinic Improves Identification of Functional Impairments.

BACKGROUND: Concussions, or mild traumatic brain injuries, are prevalent among youth and young adults. These injuries may disrupt a person's daily activities (occupations) including school, physical activity, work, and socialization. Rehabilitation professionals, such as occupational therapists (OTs), are experts in providing individualized intervention to address these temporary life changes during recovery. OBJECTIVE: This article aims to identify the benefit of having an occupational therapy practitioner on an interdisciplinary treatment team when providing intervention to patients with concussion. SETTING: Concussion clinic at an academic institution. PARTICIPANTS: Participants ages 12 to 24 years with a reported history of mild traumatic brain injury or concussion were evaluated by a physician, or by a physician and OT, in an initial evaluation appointment. DESIGN: A single researcher (OT) with training in concussion qualitatively compared reported impacted occupational domains as defined in the Occupational Therapy Practice Framework, using both a retrospective and a prospective cohort. The prospective group differed from the retrospective group in that an OT was present, and participated in the initial evaluation. RESULTS: The domains of performance patterns (P = .007) and performance skills (P ≤ .001) were identified significantly more often when an occupational therapy practitioner participated in the initial evaluation. CONCLUSIONS: Rehabilitation professionals, such as OTs, play an important role in identifying impacted domains after a concussion, which can help optimize patient care.

Acute glucose and lactate metabolism are associated with cognitive recovery following traumatic brain injury.

Traumatic brain injury (TBI) is associated with acute cerebral metabolic crisis (ACMC). ACMC-related atrophy appears to be prominent in frontal and temporal lobes following moderate-to-severe TBI. This atrophy is correlated with poorer cognitive outcomes in TBI. The current study investigated ability of acute glucose and lactate metabolism to predict long-term recovery of frontal-temporal cognitive function in participants with moderate-to-severe TBI. Cerebral metabolic rate of glucose and lactate were measured by the Kety-Schmidt method on days 0-7 post-injury. Indices of frontal-temporal cognitive processing were calculated for six months post-injury; 12 months post-injury; and recovery (the difference between the six- and 12-month scores). Glucose and lactate metabolism were included in separate regression models, as they were highly intercorrelated. Also, glucose and lactate values were centered and averaged and included in a final regression model. Models for the prediction frontal-temporal cognition at six and 12 months post-injury were not significant. However, average glucose and lactate metabolism predicted recovery of frontal-temporal cognition, accounting for 23% and 22% of the variance, respectively. Also, maximum glucose metabolism, but not maximum lactate metabolism, was an inverse predictor in the recovery of frontal-temporal cognition, accounting for 23% of the variance. Finally, the average of glucose and lactate metabolism predicted frontal-temporal cognitive recovery, accounting for 22% of the variance. These data indicate that acute glucose and lactate metabolism both support cognitive recovery from TBI. Also, our data suggest that control of endogenous fuels and/or supplementation with exogenous fuels may have therapeutic potential for cognitive recovery from TBI.

Metabolic crisis occurs with seizures and periodic discharges after brain trauma.

OBJECTIVE: Traumatic brain injury (TBI) results in persistent disruption of brain metabolism that has yet to be mechanistically defined. Early post-traumatic seizures are one potential mechanism for metabolic crisis and hence could be a therapeutic target. We hypothesized that seizures and pseudoperiodic discharges (PDs) may be mechanistically linked to metabolic crisis as measured by cerebral microdialysis. METHODS: A prospective multicenter study of surface and intracortical depth electroencephalography (EEG) was performed in conjunction with cerebral microdialysis in a cohort of severe TBI patients with time-locked analysis of the neurochemical response to seizures and pseudoperiodic discharges. RESULTS: Seizures or PDs occurred in 61% of 34 subjects, with 42.9% of these seizures noted only on intracortical depth EEG and in some cases lasting for many hours. Metabolic crisis as measured by elevated cerebral microdialysis lactate/pyruvate ratio occurred during seizures or PDs but not during electrically nonepileptic epochs. INTERPRETATION: In TBI patients, seizures and periodic discharges are one mechanism for metabolic crisis, and hence represent a therapeutic target for future study.

Influence of Glycemic Control on Endogenous Circulating Ketone Concentrations in Adults Following Traumatic Brain Injury.

BACKGROUND: The objective was to investigate the impact of targeting tight glycemic control (4.4-6.1 mM) on endogenous ketogenesis in severely head-injured adults. METHODS: The data were prospectively collected during a randomized, within-patient crossover study comparing tight to loose glycemic control, defined as 6.7-8.3 mM. Blood was collected periodically during both tight and loose glycemic control epochs. Post hoc analysis of insulin dose and total nutritional provision was performed. RESULTS: Fifteen patients completed the crossover study. Total ketones were increased 81 µM ([38 135], p < 0.001) when blood glucose was targeted to tight (4.4-6.1 mM) compared with loose glycemic control (6.7-8.3 mM), corresponding to a 60 % increase. There was a significant decrease in total nutritional provisions (p = 0.006) and a significant increase in insulin dose (p = 0.008). CONCLUSIONS: Permissive underfeeding was tolerated when targeting tight glycemic control, but total nutritional support is an important factor when treating hyperglycemia.

Rehabilitation of hand function after spinal cord injury using a novel handgrip device: a pilot study.

BACKGROUND: Activity-based therapy (ABT) for patients with spinal cord injury (SCI), which consists of repetitive use of muscles above and below the spinal lesion, improves locomotion and arm strength. Less data has been published regarding its effects on hand function. We sought to evaluate the effects of a weekly hand-focused therapy program using a novel handgrip device on grip strength and hand function in a SCI cohort. METHODS: Patients with SCI were enrolled in a weekly program that involved activities with the MediSens (Los Angeles, CA) handgrip. These included maximum voluntary contraction (MVC) and a tracking task that required each subject to adjust his/her grip strength according to a pattern displayed on a computer screen. For the latter, performance was measured as mean absolute accuracy (MAA). The Spinal Cord Independence Measure (SCIM) was used to measure each subject's independence prior to and after therapy. RESULTS: Seventeen patients completed the program with average participation duration of 21.3 weeks. The cohort included patients with American Spinal Injury Association (ASIA) Impairment Scale (AIS) A (n = 12), AIS B (n = 1), AIS C (n = 2), and AIS D (n = 2) injuries. The average MVC for the cohort increased from 4.1 N to 21.2 N over 20 weeks, but did not reach statistical significance. The average MAA for the cohort increased from 9.01 to 21.7% at the end of the study (p = .02). The cohort's average SCIM at the end of the study was unchanged compared to baseline. CONCLUSIONS: A weekly handgrip-based ABT program is feasible and efficacious at increasing hand task performance in subjects with SCI.

Therapeutic intravascular normothermia reduces the burden of metabolic crisis.

BACKGROUND: We aim to investigate whether therapeutic-induced normothermia (TIN) ≤ 37.5 °C, by means of intravascular cooling devices is more efficacious than standard medical therapy (MED) in alleviating metabolic crisis (MC) acutely following traumatic brain injury (TBI). METHODS: We retrospectively analyzed data from 62 patients with severe TBI, GCS ≤ 8. We divided the cohort into two groups. (1) Patients who had temperature controlled via standard medical therapies (n = 52), (2) TIN group (n = 10). For each group, we analyzed the percent time spent in normothermia, and in MC. Furthermore, we focused the investigation on pre-TIN versus post-TIN comparing temp, intracranial pressure (ICP), sedation, and MC before and after intravascular cooling. RESULTS: TIN patients had a better temperature control than MED group (60.72 ± 19.53 vs 69.75 ± 24.98 %, p < 0.001) and spent shorter time in MC (22.60 ± 20.45 vs 32.17 ± 27.25 %, p < 0.001). Temperature control was associated with reduced incidence of MC in TIN (OR 0.51, CI 0.38-0.67, p < 0.001, p < 0.001) but not in MED (OR 0.97, CI 0.87-1.1, p = 0.63). Within TIN group analysis, following TIN both temperature and incidence of MC improved from 37.62 ± 0.34 versus 36.69 ± 0.90 °C (p < 0.005) and 41.95 ± 27.74 % before to 8.35 ± 9.78 % (p = 0.005) after, respectively. ICP was well controlled both before and after intravascular cooling (13.07 vs 15.83 mmHg, p = 0.20). CONCLUSION: Therapeutic normothermia, using intravascular cooling, results in a reduction in the burden of MC. This differential effect occurs despite equivalent control of ICP in both TIN and MED treatments. These results demonstrate proof of concept of normothermia, when applied in a controlled manner, being neuroprotective.

The pituitary stalk effect: is it a passing phenomenon?

Most patients with large pituitary tumors do not exhibit hyperprolactinemia as a result of pituitary lactotroph disinhibition (stalk effect). Studies have demonstrated that increased intrasellar pressure is associated with both "stalk effect" hyperprolactinemia and pituitary insufficiency. Our primary hypothesis was that, despite continued disinhibition, lactotroph failure is responsible for normoprolactinemia in patients with large macroadenomas. As a corollary, we proposed that the hyperprolactinemia phase, which presumably would precede the insufficiency/normoprolactinemic state, would more likely be discovered in premenopausal females and go unnoticed in males. Prospective, consecutive surgical series of 98 patients of clinically nonfunctional pituitary adenomas. Lactotroph insufficiency was inferred by the coexistence of insufficiency in another pituitary axis. The existence of pre-operative lactotroph disinhibition was inferred based on comparison of pre- versus post-operative prolactin levels. 87 % of patients with tumor size >20 mm and normoprolactinemia had pituitary insufficiency. Pre-operative prolactin in patients with pituitary insufficiency were lower than those with intact pituitary function. Prolactin levels dropped in nearly all patients, including patients with normoprolactinemia pre-operatively. Premenopausal women had smaller tumors and higher pre-operative prolactin levels compared to males. No premenopausal female exhibited evidence of pituitary insufficiency. Our study provides suggestive evidence that the "stalk effect" pathophysiology is the norm rather than the exception, and that the finding of normoprolactinemia in a patient with a large macroadenoma is likely a consequence of lactotroph insufficiency. In males, the hyperprolactinemia window is more likely to be missed clinically due to an absence of prolactin-related symptoms.

Public transport accessibility indicators to urban and regional services in Great Britain.

Public transport accessibility to urban and regional services has been found to relate to various social and economic processes, such as unemployment, transport mode choice, property prices, and public health. A frequent type of measures representing accessibility are location-based. While these offer advantages, like flexibility and ease of interpretation, their estimation usually requires specialized skills and substantial computational resources. To lower these barriers, we have prepared a suite of accessibility indicators for key services across Great Britain at a spatially disaggregated level. The dataset includes ready-to-use public transport accessibility indicators for employment, general practitioners (GP, or family physician), hospitals, grocery stores, supermarkets, primary and secondary schools, and urban centres. It also includes the raw travel time matrix from each origin to every potential destination, a primary input for such indicator estimation. Altogether, this resource offers various levels of application, from direct input into a range of research topics to the foundation for creating comprehensive custom indicators.

Enhancing our understanding of short-term rental activity: A daily scrape-based approach for Airbnb listings.

The growth of the online short-term rental market, facilitated by platforms such as Airbnb, has added to pressure on cities' housing supply. Without detailed data on activity levels, it is difficult to design and evaluate appropriate policy interventions. Up until now, the data sources and methods used to derive activity measures have not provided the detail and rigour needed to robustly carry out these tasks. This paper demonstrates an approach based on daily scrapes of the calendars of Airbnb listings. We provide a systematic interpretation of types of calendar activity derived from these scrapes and define a set of indicators of listing activity levels. We exploit a unique period in short-term rental markets during the UK's first COVID-19 lockdown to demonstrate the value of this approach.

Association of Premorbid Anxiety and Depression Symptoms in Concussion Recovery in Collegiate Student-Athletes.

BACKGROUND: Mental health disorders are linked to prolonged concussion symptoms. However, the association of premorbid anxiety/depression symptoms with postconcussion return-to-play timelines and total symptom burden is unclear. OBJECTIVE: To examine the association of self-reported premorbid anxiety/depression symptoms in collegiate student-athletes with (1) recovery times until asymptomatic, (2) return-to-play, and (3) postconcussion symptom burden. STUDY DESIGN: Athletes in the Concussion Assessment, Research and Education Consortium completed baseline concussion assessments (Sport Concussion Assessment Tool [SCAT3] and Brief Symptom Inventory-18 [BSI-18]). Athletes were tested postinjury at <6 hours, 24 to 48 hours, time of asymptomatic and start of return-to-play protocol, unrestricted return-to-play, and 6 months after injury. Injured athletes were categorized into 4 groups based on BSI-18 scores: (1) B-ANX, elevated anxiety symptoms only; (2) B-DEP, elevated depression symptoms only; (3) B-ANX&DEP, elevated anxiety and depression symptoms; and (4) B-NEITHER, no elevated anxiety or depression symptoms. Relationship between age, sex, BSI-18 group, SCAT3 total symptom and severity scores, and time to asymptomatic status and return-to-play was assessed with Pearson's chi-squared test and robust analysis of variance. LEVEL OF EVIDENCE: Level 3. RESULTS: Among 1329 athletes with 1352 concussions, no respondents had a self-reported premorbid diagnosis of anxiety/depression. There was no difference in time until asymptomatic or time until return-to-play between BSI-18 groups (P = 0.15 and P = 0.11, respectively). B-ANX, B-DEP, and B-ANX&DEP groups did not have higher total symptom or severity scores postinjury compared with the B-NEITHER group. CONCLUSION: Baseline anxiety/depression symptoms in collegiate student-athletes without a mental health diagnosis are not associated with longer recovery times until asymptomatic, longer time to return-to-play, or higher postconcussion total symptom and severity scores compared with athletes without baseline symptoms. CLINICAL RELEVANCE: Anxiety and depression symptoms without a clear mental health diagnosis should be considered differently from other comorbidities when discussing prolonged recovery in collegiate student-athletes.