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Mucormycosis is an opportunistic fungal infection with a high mortality rate. Though typically associated with diabetes and other conditions that affect innate immune function, infections can also be precipitated by conditions such as trauma and burns. Burn patients are particularly susceptible to fungal infections due to the immune dysfunction that often accompany their wounds. Indeed case series have described mucormycosis to occur in patients with burn injuries, however the factors contributing to mortality have not been well described. Thus, the purpose of our review was to identify factors contributing to morbidity and mortality in burn patients with Mucormycosis.A systematic review of the literature of mucormycosis infection in burn injury patients was performed on Pubmed and Google Scholar using the keywords: Mucor, Mucorales, Mucormycosis, Mucormycotina, Zygomycosis and burn or thermal injury. Clinical trials, observational studies, case reports, and case reviews were included if they provided information regarding mortality in adult and pediatric burn patients diagnosed with mucormycosis, review articles, non-English articles, and articles without patient information were excluded. No time limit was placed on our review. Individual patient data was stratified based on mortality. Statistical analysis was performed to investigate the relationship between patient risk factors and mortality, and the Oxford Level of Evidence was used to evaluate study quality.46 articles were included in our final review, encompassing 114 patients. On average, survivors had a total body surface area (TBSA)% of 46 (SD 19.8) while non-survivors had a TBSA of 65% (SD 16.4), and this difference was significant (p .001). Patients with disseminated mucormycosis experienced an 80% mortality rate compared to 36% mortality rate in patients with localized disease (p .001). We found no statistically significant difference in mean age (p .05), diabetes (p .05), mean delay in diagnosis (p .05), time to antifungal therapy (p .05), or type of therapy used (p .05) between survivors and non-survivors. Our review was limited by the lack of prospective, controlled trials; thus, our review primarily consists of case reports.Disseminated infections and higher TBSA both increased the risk of mortality in burn patients with mucormycosis, while diabetes did not increase mortality risk. The severity of the initial injury and infection locations must be taken into consideration to inform patient prognosis.

Background Microvascular hepatic artery reconstruction (MHAR) is associated with decreased rates of hepatic artery thrombosis (HAT) in living donor liver transplantation (LDLT). There is a paucity of literature describing the learning points and initiation of this technique at the institutional level. The objective of this study is to report our institutional experience using MHAR in adult LDLT with a focus on technique and outcomes. Methods A retrospective review of adult patients who underwent LDLT from January 2012 to December 2020 was conducted. Patients were divided into two groups, those who underwent LDLT without MHAR and with MHAR. We analyzed cases for technical data including donor and recipient artery characteristics, anastomotic techniques, intraop events, and postop complications. A Mann–Whitney test was performed to compare outcomes between non-MHAR and MHAR patients. Results Fifty non-MHAR and 50 MHAR patients met inclusion criteria. Median age at transplantation was 58 (interquartile range [IQR] 11.8) and 57.5 years (IQR 14.5), respectively. Median follow-up for MHAR patients was 12.8 months (IQR 11.6). The most common recipient arteries were the right hepatic artery (HA) (58%) and left HA (20%). Median size of recipient and donor arteries were 3.3 mm (IQR 0.7) and 3.1 mm (IQR 0.7), resulting in a median mismatch size of 0.3 mm (IQR 0.4). Median microanastomosis time was 44 minutes (IQR 0). HAT, graft failure, and mortality rates were higher in the non-MHAR cohort (6% vs. 0%, 8% vs. 0%, and 16% vs. 6%, respectively); however, these did not reach statistical significance. Conclusion This study found lower rates of HAT and graft failure after implementing MHAR, though statistical significance was not achieved. Larger cohort studies are needed to further assess the potential benefit of MHAR in adult LDLT. From our experience, MHAR requires cooperation between the transplant and microsurgical teams, with technical challenges overcome with appropriate instrumentation and planning.

Objectives To determine the efficacy and safety of blue-light therapy in seasonal and non-seasonal major depressive disorder (MDD), by comparison to active and inactive control conditions. Methods We searched Web of Science, EMBASE, Medline, PsycInfo, and Clinicaltrials.gov through January 17, 2022, for randomized controlled trials (RCTs) using search terms for blue/blue-enhanced, light therapy, and depression/seasonal affective disorder. Two independent reviewers extracted data. The primary outcome was the difference in endpoint scores on the Structured Interview Guide for the Hamilton Depression Rating Scale - Seasonal Affective Disorder (SIGH-SAD) or the Structured Interview Guide for the Hamilton Depression Rating Scale with Atypical Depression Supplement (SIGH-ADS) between blue light and comparison conditions. Secondary outcomes were response (≥ 50% improvement from baseline to endpoint on a depression scale) and remission rates (endpoint score in the remission range). Results Of 582 articles retrieved, we included nine RCTs ( n = 347 participants) assessing blue-light therapy. Seven studies had participants with seasonal MDD and two studies included participants with non-seasonal MDD. Four studies compared blue light to an inactive light condition (efficacy studies), and five studies compared it to an active condition (comparison studies). For the primary outcome, a meta-analysis with random-effects models found no evidence for the efficacy of blue-light conditions compared to inactive conditions (mean difference [MD] = 2.43; 95% confidence interval [CI], −1.28 to 6.14, P = 0.20); however, blue-light also showed no differences compared to active conditions (MD = −0.11; 95% CI, −2.38 to 2.16, P = 0.93). There were no significant differences in response and remission rates between blue-light conditions and inactive or active light conditions. Blue-light therapy was overall well-tolerated. Conclusions The efficacy of blue-light therapy in the treatment of seasonal and non-seasonal MDD remains unproven. Future trials should be of longer duration, include larger sample sizes, and attempt to better standardize the parameters of light therapy.

Burn wound depth assessments are an important component of determining patient prognosis and making appropriate management decisions. Clinical appraisal of the burn wound by an experienced burn surgeon is standard of care but has limitations. Infrared (IR) thermography is a technology in burn care that can provide a noninvasive, quantitative method of evaluating burn wound depth. IR thermography utilizes a specialized camera that can capture the IR emissivity of the skin, and the resulting images can be analyzed to determine burn depth and healing potential of a burn wound. Though IR thermography has great potential for burn wound assessment, its use for this has not been well documented. Thus, we have conducted a systematic review of the current use of IR thermography to assess burn depth and healing potential. A systematic review and meta-analysis of the literature was performed on PubMed and Google Scholar between June 2020 and December 2020 using the following keywords: FLIR, FLIR ONE, thermography, forward looking infrared, thermal imaging + burn*, burn wound assessment, burn depth, burn wound depth, burn depth assessment, healing potential, burn healing potential. A meta-analysis was performed on the mean sensitivity and specificity of the ability of IR thermography for predicting healing potential. Inclusion criteria were articles investigating the use of IR thermography for burn wound assessments in adults and pediatric patients. Reviews and non-English articles were excluded. A total of 19 articles were included in the final review. Statistically significant correlations were found between IR thermography and laser Doppler imaging (LDI) in 4/4 clinical studies. A case report of a single patient found that IR thermography was more accurate than LDI for assessing burn depth. Five articles investigated the ability of IR thermography to predict healing time, with four reporting statistically significant results. Temperature differences between burnt and unburnt skin were found in 2/2 articles. IR thermography was compared to clinical assessment in five articles, with varying results regarding accuracy of clinical assessment compared to thermography. Mean sensitivity and specificity of the ability of IR thermography to determine healing potential

Burn wounds are most commonly evaluated through visual inspection to determine surgical candidacy, taking into account burn depth and individualized patient factors. This process, though cost effective, is subjective and varies by provider experience. Deep learning models can assist in burn wound surgical candidacy with predictions based on the wound and patient characteristics. To this end, we present a multimodal deep learning approach and a complementary mobile application – DL4Burn – for predicting burn surgical candidacy, to emulate the multi-factored approach used by clinicians. Specifically, we propose a ResNet50-based multimodal model and validate it using retrospectively obtained patient burn images, demographic, and injury data.

Auditory attention allows us to focus on relevant target sounds in the acoustic environment while maintaining the capability to orient to unpredictable (novel) sound changes. An open question is whether orienting to expected vs. unexpected auditory events are governed by anatomically distinct attention pathways, respectively, or by differing communication patterns within a common system. To address this question, we applied a recently developed PeSCAR analysis method to evaluate spectrotemporal functional connectivity patterns across subregions of broader cortical regions of interest (ROIs) to analyze magnetoencephalography data obtained during a cued auditory attention task. Subjects were instructed to detect a predictable harmonic target sound embedded among standard tones in one ear and to ignore the standard tones and occasional unpredictable novel sounds presented in the opposite ear. Phase coherence of estimated source activity was calculated between subregions of superior temporal, frontal, inferior parietal, and superior parietal cortex ROIs. Functional connectivity was stronger in response to target than novel stimuli between left superior temporal and left parietal ROIs and between left frontal and right parietal ROIs, with the largest effects observed in the beta band (15–35 Hz). In contrast, functional connectivity was stronger in response to novel than target stimuli in inter-hemispheric connections between left and right frontal ROIs, observed in early time windows in the alpha band (8–12 Hz). Our findings suggest that auditory processing of expected target vs. unexpected novel sounds involves different spatially, temporally, and spectrally distributed oscillatory connectivity patterns across temporal, parietal, and frontal areas.

Pain following burn injury is associated with long-term health consequences in the pediatric population. Literature suggests nonpharmacologic treatment may provide improved pain control as an effective adjunct for these patients. This study aims to summarize randomized controlled trials on nonpharmacologic procedural pain management in pediatric burn patients. A systematic review was conducted on nonpharmacologic procedural pain management techniques used in the pediatric burn population. Fifteen studies were included and involved virtual reality, distraction devices, child life therapy, directed play, digital tablet games, cartoons, hypnosis, and music therapy. Treatment was effective in 8 out of 15 studies. Compared to controls, nonpharmacologic treatments reduced mid procedure pain by 19.7% and post-procedure pain by 20.1%. This study demonstrates that nonpharmacologic therapy can be an effective adjunct in pediatric procedural burn pain management, however further studies are needed to develop standardized algorithms to integrate nonpharmacologic treatments with pharmacologic therapies.

Introduction The most significant sequelae of foot burns in diabetic patients is a non-healing wound that results in a diabetic foot ulcer, which has been a predictor for need for amputation and mortality. Even minor amputations in patients with diabetes have a significant mortality rate. Our systemic review found that when 60% of a diabetic patient cohort with foot burns was managed by skin grafting, 29% subsequently required amputations, which is concerning. The practice at our regional burn center has been to manage patients with foot burns and diabetes non-operatively with daily dressing changes, and we believe that this may result in better functional outcomes, ambulatory status, and lower amputation rates. Methods A retrospective review of patients with diabetes and foot burns admitted to an ABA verified regional burn center was conducted. The primary outcome was amputation. Secondary outcomes were ambulatory status, wound closure, and infection. Rank sum and fisher exact tests were performed to compare patient demographics, comorbidities, uncontrolled DM (A1c >9%), and burn characteristics between patients who were treated surgically and those who received daily wound care only. These associations were subsequently evaluated with odds ratios (OR) and 95% confidence intervals (CI). A multivariable logistic regression was performed to evaluate for possible differentiating factors that resulted in maintaining ambulatory status at completion of burn care. Statistical significance was defined as p< .05. Results Of 75 patients identified, median TBSA burned was 2% (IQR 2), and 61% (n=46) had full thickness burns. Mean A1c at admission was 9% (SD 2). In terms of management, 9% (n=7) were treated with debridement and/or skin grafting, and 9% (n=7) later required lower extremity amputations. Infection during first admission developed in 8% (n=6). At completion of burn care, 73% had normal or same ambulatory status, and older patients were less likely to maintain ambulatory status (p=.009, OR=0.92, 95% CI=0.86-0.98). Median time to wound closure was 95 (IQR 130) days, and 12% (n=9) of wounds never fully closed. Burn depth (second vs third degree), burn location (plantar burn vs other areas), uncontrolled DM, and surgical treatment did not result in a statistically significant difference in maintaining ambulatory status at completion of burn care. Conclusions Diabetic patients with foot burns are best managed non-operatively with daily dressing changes, and should be allowed to heal secondarily. This may result in a longer time to close the wounds, but the amputation rates were much lower when compared to surgical management. However, 5% of our cohort developed diabetic foot ulcers at completion of burn care, which is a complex disease process that carries a dire prognosis.

Tattoos of formerly gang-involved and incarcerated individuals can negatively impact their ability to reintegrate into society. Laser tattoo removal is essential to helping individuals obtain employment, re-cultivate positive relationships, and disengage from gangs. The objective of this study is to describe the demographics and motivations for laser tattoo removal at a large nonprofit clinic. This was a single center retrospective study conducted on patients presenting to Ya’stuvo Tattoo Removal between January 2016-December 2018 and had at least three laser tattoo removal sessions. Data was recorded on patient demographics, geographic location of residence (e.g. zipcode), comorbidities, probation/parole status, referral source, transportation mode, and motivations for receiving and removing tattoos. A representative sample of 862 patients was used to conduct our analysis. Average age at first visit was 30. 16% (n = 134) were on probation, 8% (n = 66) were on parole, and 63% (n = 544) did not report their probation/parole status. Reasons for receiving a tattoo included gangs (46%, n = 368), a current or ex-relationship (28%, n = 223), and decoration (20%, n = 159). The most common reasons for tattoo removal were employment (66%, n = 546), readiness to change life (47%, n = 392), maturity (47%, n = 392), family (43%, n = 356), and negative attention from tattoos (37%, n = 303). The current study highlights the importance of laser tattoo removal in reintegration and gang disengagement. Expanding cost efficient laser tattoo removal is paramount to meet the safety and socioeconomic needs of this population.

PURPOSE: Rapid sequence intubation (RSI) in trauma patients is common; however, the induction agents used have been debated. We determined which induction medications were used most frequently for adult trauma RSIs and their associations with hemodynamics and outcomes. We hypothesized that etomidate is the most commonly used induction agent and has similar outcomes to other induction agents. METHODS: This retrospective review at two U.S. level I trauma centers evaluated adult trauma patients undergoing RSI within 24h of admission, between 01/01/2016 and 12/31/2017. We compared patient characteristics and outcomes by induction agent. Comparisons on the primary outcome of in-hospital mortality and secondary outcomes of peri-intubation hypotension, hospital and ICU length of stay (LOS), ventilator days, and complications used logistic regression or negative binomial regression. Regression models adjusted for hospital site, age, patient severity measures, and intubation location. RESULTS: Among 1303 trauma patients undergoing RSI within 24h of admission, 948 (73%) were intubated in the emergency department (ED) and 325 (25%) in the operating room (OR). The most common induction agents were etomidate (68%), propofol (17%), and ketamine (11%). In-hospital mortality was highest in the etomidate group (25.5%), followed by ketamine (17%), and propofol (1.8%). CONCLUSION: Etomidate was most commonly used in ED intubations; propofol was most used in the OR. Compared to propofol, patients induced with etomidate had higher mortality and complication rates. Findings should be interpreted with caution given limited generalizability and residual confounding by indication.

Tent fires are a growing issue in regions with large homeless populations given the rise in homelessness within the United States and existing data that suggest worse outcomes in this population. The aim of this study was to describe the characteristics and outcomes of tent fire burn injuries in the homeless population. A retrospective review was conducted involving two verified regional burn centers with patients admitted for tent fire burns between January 2015 and December 2020. Variables recorded include demographics, injury characteristics, hospital course, and patient outcomes. Sixty-nine patients met the study inclusion criteria. The most common mechanisms of injury were by portable stove accident, assault, and tobacco or methamphetamine related. Median percent total body surface area (%TBSA) burned was 6% (interquartile range [IQR] 9%). Maximum depth of injury was partial thickness in 65% (n = 45) and full thickness in 35% (n = 24) of patients. Burns to the upper and lower extremities were present in 87% and 54% of patients, respectively. Median hospital length of stay (LOS) was 10 days (IQR = 10.5) and median ICU LOS was 1 day (IQR = 5). Inhalation injury was present in 14% (n = 10) of patients. Surgical intervention was required in 43% (n = 30) of patients, which included excision, debridement, skin grafting, and escharotomy. In-hospital mortality occurred in 4% (n = 3) of patients. Tent fire burns are severe enough to require inpatient and ICU level of care. A high proportion of injuries involved the extremities and pose significant barriers to functional recovery in this vulnerable population. Strategies to prevent these injuries are paramount.

Background Visual evaluation is the most common method of evaluating burn wounds. Its subjective nature can lead to inaccurate diagnoses and inappropriate burn center referrals. Machine learning may provide an objective solution. The objective of this study is to summarize the literature on ML in burn wound evaluation. Methods A systematic review of articles published between January 2000 and January 2021 was performed using PubMed and MEDLINE (OVID). Articles reporting on ML or automation to evaluate burn wounds were included. Keywords included burns, machine/deep learning, artificial intelligence, burn classification technology, and mobile applications. Data were extracted on study design, method of data acquisition, machine learning techniques, and machine learning accuracy. Results Thirty articles were included. Nine studies used machine learning and automation to estimate percent total body surface area (%TBSA) burned, 4 calculated fluid estimations, 19 estimated burn depth, 5 estimated need for surgery, and 2 evaluated scarring. Models calculating %TBSA burned demonstrated accuracies comparable to or better than paper methods. Burn depth classification models achieved accuracies of >83%. Conclusion Machine learning provides an objective adjunct that may improve diagnostic accuracy in evaluating burn wound severity. Existing models remain in the early stages with future studies needed to assess their clinical feasibility.

Introduction Thorough documentation is an important component of delivering quality patient care. Documentation of common data elements (CDE), defined as a precise question with a specified set of responses used across multiple databases or studies, can also assist in improving data collection. Currently, burn care does not have an existing set of CDEs despite their potential to be a reproducible and reliable system for data collection which leads to improved burn care. Our institution performed a retrospective review of patient charts to identify the consistency of our burn care documentation and highlight deficits that could be remedied by the implementation of CDEs. Methods This was a single-center retrospective review of patient charts from 2014-2019. Thirty-three CDEs were investigated. Two hundred four patient charts were randomly selected for review. We presented extracted CDEs as frequencies and percentages. Information was obtained from the history and physical notes, progress notes, and discharge summaries. Results Our review yielded 204 patient records. The note/record of some data points could not be identified and were excluded from the qualitative calculation. Of the data points that included more than 200 records, 86% percent specified the date of injury, 88% recorded the admission date, 99% reported burn etiology, 94% included total body surface area (TBSA) burned, 94% included burn thickness, 99% specified anatomic injury location, 97% included information about wound care agents/dressings, and 24% recorded the patient’s pain scores. Thirty percent (49/164) reported the presence or absence of inhalation injury. Twenty-six percent (38/148) listed reported presence or absence of non-burn related injuries. Sixty-four percent (127/200) reported presence or absence of comorbid conditions. Other data points were found with varying frequencies (Table 1). Conclusions Consistent documentation of burn care remains challenging and many variables are collected inconsistently. Our results highlight the need for CDEs in burn care to standardize documentation.

Introduction Homelessness is a rising concern as insufficient housing and significant barriers to shelter has led to more individuals seeking shelter in tents. Within this demographic there has been an increased trend of burn injuries from tent fires in regions with large homeless populations. This represents a public health crisis given the long-term psychosocial and functional sequela of burn injuries and existing data that suggest worse outcomes in the homeless population. To our knowledge, homeless related tent fire burns have not previously been studied in the literature. The aim of this study is to describe the characteristics and outcomes of tent fire burn injuries in the homeless population. Methods A retrospective cohort study was conducted involving two verified regional burn centers with patients admitted for tent fire burns between January 1, 2019 to July 31, 2020. Patients were identified as either domiciled or homeless based on medical records at the time of injury. Variables recorded include demographics, injury characteristics, hospital course, and patient outcomes. Results A total of 45 patients were identified. The most common mechanisms of injury were by portable stove accident (29%), assault (27%), bonfire (22%), and tobacco or methamphetamine paraphernalia-related (16%). Median percent total body surface area (%TBSA) burned was 5.5 (IQR 5.5). Maximum depth of injury was second degree in 62% (n=28) of patients and third degree in 38% (n=17) of patients. Burns to the upper extremities were present in 84% of patients and burns to the lower extremities were present in 53% of patients. Median hospital LOS was 9.5 days (IQR=10) and median ICU LOS was 2 days (IQR=4.8), with inhalation injury present in 16% (n=7) of patients. Surgical intervention was required in 40% (n=18) of patients, which included debridement, skin grafting, and escharotomy. In-hospital mortality occurred in 5% (n=2) of patients. Conclusions Burn injuries from tent fires incur significant injury burden to an already vulnerable population, with risk factors that predispose them to poor burn outcomes. Injuries in our cohort were severe enough to require inpatient and ICU level of care. We saw a high proportion of injuries to the extremities, which pose functional and psychosocial challenges to the wellbeing of these patients. Further resources are needed to better prevent tent fires and care for this population.

Introduction Burn wound depth assessments are an important component of determining patient prognosis and making appropriate management decisions. Clinical appraisal of the burn wound by an experienced burn surgeon is standard of care but has limitations. Forward-looking Infrared (FLIR) is a new technology in burn care that can provide a non-invasive, quantitative method of evaluating burn wound depth. FLIR utilizes a specialized camera that can capture the infrared emissivity of the skin, and the resulting images can be analyzed to determine burn depth and healing potential of a burn wound. Though FLIR has great potential for burn wound assessment, its use for this has not been well documented. Thus, we have conducted a systematic review and meta-analysis of the current use of FLIR technology to assess burn depth and healing potential. Methods A systematic review of the literature was performed on PubMed and Google Scholar between June 2020-August 2020 using the following keywords: thermal imaging, FLIR, forward looking infrared, burn, burn depth. Meta-analysis was performed on the mean sensitivity and specificity of the ability of FLIR to predict healing potential. Inclusion criteria were articles investigating the use of FLIR for burn wound assessments in adults, pediatric patients and animal models. Reviews and non-English articles were excluded. Results A total of 11 articles were included in the final review. Statistically significant correlations were found between FLIR and laser doppler imaging (LDI) in 3/3 clinical studies. A case report of a single patient found that FLIR was more accurate than LDI for assessing burn depth. Three articles investigated the ability of FLIR to predict healing potential, with all three reporting statistically significant results. Significant temperature differences between burnt and unburnt skin were found in 2/2 articles. FLIR was compared to clinical assessment by burn surgeons in two articles; one article found that FLIR was more accurate for assessing burn depth, while the other article found that clinical assessment was more accurate for predicting healing potential < 21 days. Mean sensitivity and specificity of the ability of FLIR to determine healing potential < 15 days was 44.5 and 98.8 respectively. Mean sensitivity and specificity of the ability of FLIR to determine healing potential < 21 days was 44.0 and 77.4 respectively. Conclusions FLIR is an accurate, simple, and cost-effective method of burn wound assessment. FLIR has been demonstrated to have significant correlations with other methods of assessing burns such as LDI and can be utilized to accurately assess burn depth and healing potential.

Introduction Pain is a universal feature of pediatric burns that is associated with long-term mental health consequences in this population. While pharmacologic therapy can alleviate pain, it does not always provide complete control and carries its own risks. Current literature suggests nonpharmacologic treatment may provide improved pain control as an effective adjunct in pediatric burn patients. The aim of this systematic review is to summarize the literature of nonpharmacologic pain management in pediatric burn patients. Methods A systematic review was conducted using PubMed, Ovid MEDLINE, Scopus, and Web of Science. Keywords included: analgesia, pain, children, pediatric, paediatric, child, young, adolescent, burn, and scald. Papers were included if they were randomized, controlled, had original data, collected pain scores as a function of nonpharmacologic treatment, and were conducted on pediatric burn patients. Reviews, case reports, and opinion papers were excluded. Data were extracted on pain scale, pain score during and after treatment, and significance of results. Pain reduction was calculated as the percent difference between experimental and control pain scores, and treatments with significant pain reduction were considered effective. Results Sixteen studies were included, with nonpharmacologic treatments categorized as interactive (n=12) or passive (n=4). Interactive treatments required patient activity throughout treatment and included virtual reality (n=6), distraction devices (n=3), child life therapy (n=1), directed play (n=1) and digital tablet games (n=1). Passive treatments included cartoons (n=1), hypnosis (n=1), massage therapy (n=1) and music (n=1). Mean age was 8.39 years and percent total body surface area (%TBSA) burned was 5.95%. Treatment was effective in 9 out of 16 studies. Compared to controls, nonpharmacologic treatments reduced mid procedure pain by 24.3% (n=12) and post-procedure pain by 33.6% (n=5). Of the studies reporting mid procedure pain, pain reduction was greater in interactive treatments (32.3% n=10) than in passive treatments (-15.6% n=2) (p=.016). Conclusions Nonpharmacologic therapy can be an effective adjunct in pediatric burn pain management. Significantly greater pain reduction in interactive treatments suggests distraction may lead to greater analgesia; however, the number of passive treatments for comparison was low. This study shows promise in the application of nonpharmacologic therapy, and further research will allow standardized algorithms to integrate nonpharmacologic therapy with medications.

Introduction Bioelectrical impedance analysis (BIA) is a simple, noninvasive method of assessing body composition. BIA operates by sending a low-voltage electric current through the body and measuring the impedance to that current. Parameters obtained from BIA have been used to investigate a range of variables such as nutrition and hydration status in a variety of patient populations. Phase angle is also a unique parameter that is thought to reflect cellular health. BIA parameters can undergo further analysis by bioelectrical impedance vector analysis (BIVA) which can provide information about hydration status. Burn and critical care patients pose a unique challenge because they are particularly sensitive to fluid shifts and metabolic derangements which are associated with poorer outcomes. The utility of BIA and BIVA in this patient population has not been well studied. Thus, we have conducted a systematic review and meta-analysis of the ability of BIVA and BIA parameters to assess cellular health and hydration status in critically ill adults and whether they can be correlated with outcomes. Methods A search was performed on PubMed and Google Scholar in accordance with PRISMA guidelines between June 2020-August 2020 utilizing the keywords: bioelectrical impedance analysis, critical care, critical, body composition, phase angle, water, fluid. Inclusion criteria were articles investigating the relationship between BIA, BIVA and outcomes with regards to phase angle, hydration, and fluid status in critically ill adults. Reviews, non-English articles, and studies involving pediatric patients were excluded. A meta-analysis was conducted on the correlation between mean phase angle and mortality. Results The final analysis included 21 articles; 4 articles were included in the meta-analysis. Statistically significant correlations were found between phase angle and mortality in 9/13 articles, hospital length of stay in 4/7 articles, ICU length of stay in 5/7 articles, and mechanical ventilation duration in 1/4 articles. For meta-analysis, mean phase angle in survivors and non-survivors was 4.5 and 3.9 respectively, and this difference was statistically significant (Figure 1, p< 0.01). Significant correlations were found between ECW/TBW and mortality in 4/7 articles, and BIVA derived hydration status and mortality in 6/7 articles. Conclusions BIA and BIVA may be used as a prognostic indicator for outcomes in critical care patients. Further investigations are needed to explore this relationship in the burn patient population.

Despite recent advances in auditory neuroscience, the exact functional organization of human auditory cortex (AC) has been difficult to investigate. Here, using reversals of tonotopic gradients as the test case, we examined whether human ACs can be more precisely mapped by avoiding signals caused by large draining vessels near the pial surface, which bias blood-oxygen level dependent (BOLD) signals away from the actual sites of neuronal activity. Using ultra-high field (7T) fMRI and cortical depth analysis techniques previously applied in visual cortices, we sampled 1 mm isotropic voxels from different depths of AC during narrow-band sound stimulation with biologically relevant temporal patterns. At the group level, analyses that considered voxels from all cortical depths, but excluded those intersecting the pial surface, showed (a) the greatest statistical sensitivity in contrasts between activations to high vs. low frequency sounds and (b) the highest inter-subject consistency of phase-encoded continuous tonotopy mapping. Analyses based solely on voxels intersecting the pial surface produced the least consistent group results, even when compared to analyses based solely on voxels intersecting the white-matter surface where both signal strength and within-subject statistical power are weakest. However, no evidence was found for reduced within-subject reliability in analyses considering the pial voxels only. Our group results could, thus, reflect improved inter-subject correspondence of high and low frequency gradients after the signals from voxels near the pial surface are excluded. Using tonotopy analyses as the test case, our results demonstrate that when the major physiological and anatomical biases imparted by the vasculature are controlled, functional mapping of human ACs becomes more consistent from subject to subject than previously thought.

Introduction Nutritional support is an essential component of caring for burn patients. Burns can induce a hypermetabolic state greater than twice the normal metabolic rate which can lead to higher rates of lean tissue mass breakdown. Despite its importance, there is no clear gold standard for monitoring nutritional status in the burn and critical care population. Many current methods of assessing body composition can be costly, labor-intensive, and inaccurate. Bioelectrical impedance analysis (BIA) is a promising new technology for assessing body composition that functions by sending a low-voltage current through the body and measuring the impedance to that current. Parameters derived from BIA have been demonstrated to reflect cellular health and correlate with nutritional status. The use of BIA to assess nutritional status in the critical care and burn population has not been well investigated. Thus, we have conducted a systematic review of the use of BIA to assess nutritional status in critically ill adults. Methods A search was conducted on Pubmed and Google Scholar in accordance with PRISMA guidelines between June 2020-August 2020 utilizing the keywords: bioelectrical impedance analysis, critical care, critical, nutrition, body composition, lean body mass, phase angle, water, fluid. Inclusion criteria were articles investigating the relationship between BIA and nutritional status in critically ill adults. Reviews, non-English articles, and studies involving pediatric patients were excluded. Results Our final study included 14 articles. BIA measured muscle mass was compared to a CT scan in two studies, with both reporting a statistically significant correlation. One article compared the ability of BIA and ultrasound to assess muscle mass, and this relationship was statistically significant. BIA derived phase angle was compared to NUTRIC and Subjective Global Assessment scores in four articles with all four reporting significant correlations. BIA was also compared to biochemical markers of nutrition such as albumin and two of three articles found significant correlations. One article compared BIA with gas exchange measured by indirect calorimetry and found that BIA could accurately assess body cell mass. No articles were found comparing BIA with other common nutritional markers such as prealbumin or nitrogen balance. Conclusions BIA shows promise as a method of assessing body composition and nutritional status in the critically ill patient population.

Introduction Current methods of burn evaluation and treatment are subjective and dependent on surgeon experience, with high rates of inter-rater variability leading to inaccurate diagnoses and treatment. Machine learning (ML) and automated methods are being used to develop more objective and accurate methods for burn diagnosis and triage. Defined as a subfield of artificial intelligence that applies algorithms capable of knowledge acquisition, machine learning draws patterns from data, which it can then apply to clinically relevant tasks. This technology has the potential to improve burn management by quantitating diagnoses, improving diagnostic accuracy, and increasing access to burn care. The aim of this systematic review is to summarize the literature regarding machine learning and automated methods for burn wound evaluation and treatment. Methods A systematic review of articles available on PubMed and MEDLINE (OVID) was performed. Keywords used in the search process included burns, machine learning, deep learning, burn classification technology, and mobile applications. Reviews, case reports, and opinion papers were excluded. Data were extracted on study design, study objectives, study models, devices used to capture data, machine learning, or automated software used, expertise level and number of evaluators, and ML accuracy of burn wound evaluation. Results The search identified 592 unique titles. After screening, 35 relevant articles were identified for systematic review. Nine studies used machine learning and automated software to estimate percent total body surface area (%TBSA) burned, 4 calculated fluid requirements, 18 estimated burn depth, 5 estimated need for surgery, 6 predicted mortality, and 2 evaluated scarring in burn patients. Devices used to estimate %TBSA burned showed an accuracy comparable to or better than traditional methods. Burn depth estimation sensitivities resulted in unweighted means >81%, which increased to >83% with equal weighting applied. Mortality prediction sensitivity had an unweighted mean of 96.75%, which increased to 99.35% with equal weighting. Conclusions Machine learning and automated technology are promising tools that provide objective and accurate measures of evaluating burn wounds. Existing methods address the key steps in burn care management; however, existing data reporting on their robustness remain in the early stages. Further resources should be dedicated to leveraging this technology to improve outcomes in burn care.

Spatial and non-spatial information of sound events is presumably processed in parallel auditory cortex (AC) “what” and “where” streams, which are modulated by inputs from the respective visual-cortex subsystems. How these parallel processes are integrated to perceptual objects that remain stable across time and the source agent's movements is unknown. We recorded magneto- and electroencephalography (MEG/EEG) data while subjects viewed animated video clips featuring two audiovisual objects, a black and a gray cat. Adaptor-probe events were either linked to the same object (the black cat meowed twice in a row in the same location) or included a visually conveyed identity change (the black and then the gray cat meowed with identical voices in the same location). In addition to effects in visual (including fusiform, middle temporal or MT areas) and frontoparietal association areas, the visually conveyed object-identity change was associated with a release from adaptation of early (50–150 ms) activity in posterior ACs, spreading to left anterior ACs at 250–450 ms in our combined MEG/EEG source estimates. Repetition of events belonging to the same object resulted in increased theta-band (4–8 Hz) synchronization within the “what” and “where” pathways (e.g., between anterior AC and fusiform areas). In contrast, the visually conveyed identity changes resulted in distributed synchronization at higher frequencies (alpha and beta bands, 8–32 Hz) across different auditory, visual, and association areas. The results suggest that sound events become initially linked to perceptual objects in posterior AC, followed by modulations of representations in anterior AC. Hierarchical what and where pathways seem to operate in parallel after repeating audiovisual associations, whereas the resetting of such associations engages a distributed network across auditory, visual, and multisensory areas.

Auditory distance perception and its neuronal mechanisms are poorly understood, mainly because 1) it is difficult to separate distance processing from intensity processing, 2) multiple intensity-independent distance cues are often available, and 3) the cues are combined in a context-dependent way. A recent fMRI study identified human auditory cortical area representing intensity-independent distance for sources presented along the interaural axis (Kopco et al., PNAS, 109, 11019-11024). For these sources, two intensity-independent cues are available, interaural level difference (ILD) and direct-to-reverberant energy ratio (DRR). Thus, the observed activations may have been contributed by not only distance-related, but also direction-encoding neuron populations sensitive to ILD. Here, the paradigm from the previous study was used to examine DRR-based distance representation for sounds originating in front of the listener, where ILD is not available. In a virtual environment, we performed behavioral and fMRI experiments, combined with computational analyses to identify the neural representation of distance based on DRR. The stimuli varied in distance (15-100 cm) while their received intensity was varied randomly and independently of distance. Behavioral performance showed that intensity-independent distance discrimination is accurate for frontal stimuli, even though it is worse than for lateral stimuli. fMRI activations for sounds varying in frontal distance, as compared to varying only in intensity, increased bilaterally in the posterior banks of Heschl's gyri, the planum temporale, and posterior superior temporal gyrus regions. Taken together, these results suggest that posterior human auditory cortex areas contain neuron populations that are sensitive to distance independent of intensity and of binaural cues relevant for directional hearing.HighlightsPosterior auditory cortices (AC) are sensitive to frontally presented distance cuesThese effects are independent of intensity- and direction-related binaural cuesfMRI activations to frontal distance cues are found in the right and left ACThe frontal reverberation-related auditory distance cues are behaviorally relevant

Auditory working memory (WM) processing in everyday acoustic environments depends on our ability to maintain relevant information online in our minds, and to suppress interference caused by competing incoming stimuli. A challenge in communication settings is that the relevant content and irrelevant inputs may emanate from a common source, such as a talkative conversationalist. An open question is how the WM system deals with such interference. Will the distracters become inadvertently filtered before processing for meaning because the primary WM operations deplete all available processing resources? Or are they suppressed post perceptually, through an active control process? We tested these alternative hypotheses by measuring magnetoencephalography (MEG), EEG, and functional MRI (fMRI) during a phonetic auditory continuous performance task. Contextual WM maintenance load was manipulated by adjusting the number of "filler" letter sounds in-between cue and target letter sounds. Trial-to-trial variability of pre- and post-stimulus activations in fMRI-informed cortical MEG/EEG estimates was analyzed within and across 14 subjects using generalized linear mixed effect (GLME) models. High contextual WM maintenance load suppressed left auditory cortex (AC) activations around 250-300 ms after the onset of irrelevant phonetic sounds. This effect coincided with increased 10-14 Hz alpha-range oscillatory functional connectivity between the left dorsolateral prefrontal cortex (DLPFC) and left AC. Suppression of AC responses to irrelevant sounds during active maintenance of the task context also correlated with increased pre-stimulus 7-15 Hz alpha power. Our results suggest that under high auditory WM load, irrelevant sounds are suppressed through a "late" active suppression mechanism, which prevents short-term consolidation of irrelevant information without affecting the initial screening of potentially meaningful stimuli. The results also suggest that AC alpha oscillations play an inhibitory role during auditory WM processing.

Our ability to refocus auditory attention is vital for even the most routine day-to-day activities. Shifts in auditory attention can be initiated "voluntarily", or triggered "involuntarily" by unexpected novel sound events. Here, we employed psychophysiological interaction (PPI) analyses of auditory functional MRI data, to compare functional connectivity patterns of distinct frontoparietal cortex regions during cued voluntary versus novelty-driven involuntary auditory attention shifting. Overall, our frontoparietal seed regions exhibited significant PPI increases with auditory cortex (AC) areas during both cued and novelty-driven orienting. However, significant positive PPI patterns associated with voluntary auditory attention (cue > novel task regressor), but mostly absent in analyses emphasizing involuntary orienting (novel > cue task regressor), were observed with seeds within the frontal eye fields (FEF), superior parietal lobule (SPL), and right supramarginal gyri (SMG). In contrast, significant positive PPIs associated selectively with involuntary orienting were observed between ACs and seeds within the bilateral anterior interior frontal gyri (IFG), and left posterior IFG, SMG, and posterior cingulate cortices (PCC). We also found indices of lateralization of different attention networks: PPI increases selective to voluntary attention occurred primarily with right-hemispheric regions, whereas those related to involuntary orienting were more frequent with left-hemisphere seeds. In conclusion, despite certain similarities in PPI patterns across conditions, the more dorsal aspects of right frontoparietal cortex demonstrated wider connectivity during cued/voluntary attention shifting, whereas certain left ventral frontoparietal seeds were more widely connected during novelty-triggered/involuntary orienting. Our findings provide partial support for distinct attention networks for voluntary and involuntary auditory attention.

Based on the infamous left-lateralized neglect syndrome, one might hypothesize that the dominating right parietal cortex has a bilateral representation of space, whereas the left parietal cortex represents only the contralateral right hemispace. Whether this principle applies to human auditory attention is not yet fully clear. Here, we explicitly tested the differences in cross-hemispheric functional coupling between the intraparietal sulcus (IPS) and auditory cortex (AC) using combined magnetoencephalography (MEG), EEG, and functional MRI (fMRI). Inter-regional pairwise phase consistency (PPC) was analyzed from data obtained during dichotic auditory selective attention task, where subjects were in 10-s trials cued to attend to sounds presented to one ear and to ignore sounds presented in the opposite ear. Using MEG/EEG/fMRI source modeling, parietotemporal PPC patterns were (a) mapped between all AC locations vs. IPS seeds and (b) analyzed between four anatomically defined AC regions-of-interest (ROI) vs. IPS seeds. Consistent with our hypothesis, stronger cross-hemispheric PPC was observed between the right IPS and left AC for attended right-ear sounds, as compared to PPC between the left IPS and right AC for attended left-ear sounds. In the mapping analyses, these differences emerged at 7–13 Hz, i.e., at the theta to alpha frequency bands, and peaked in Heschl's gyrus and lateral posterior non-primary ACs. The ROI analysis revealed similarly lateralized differences also in the beta and lower theta bands. Taken together, our results support the view that the right parietal cortex dominates auditory spatial attention.

The acquisition time of BOLD contrast functional MRI (fMRI) data with whole-brain coverage typically requires a sampling rate of one volume in 1–3 s. Although the volumetric sampling time of a few seconds is adequate for measuring the sluggish hemodynamic response (HDR) to neuronal activation, faster sampling of fMRI might allow for monitoring of rapid physiological fluctuations and detection of subtle neuronal activation timing information embedded in BOLD signals. Previous studies utilizing a highly accelerated volumetric MR inverse imaging (InI) technique have provided a sampling rate of one volume per 100 ms with 5 mm spatial resolution. Here, we propose a novel modification of this technique, the echo-shifted InI, which allows TE to be longer than TR, to measure BOLD fMRI at an even faster sampling rate of one volume per 25 ms with whole-brain coverage. Compared with conventional EPI, echo-shifted InI provided an 80-fold speedup with similar spatial resolution and less than 2-fold temporal SNR loss. The capability of echo-shifted InI to detect HDR timing differences was tested empirically. At the group level (n = 6), echo-spaced InI was able to detect statistically significant HDR timing differences of as low as 50 ms in visual stimulus presentation. At the level of individual subjects, significant differences in HDR timing were detected for 400 ms stimulus-onset differences. Our results also show that the temporal resolution of 25 ms is necessary for maintaining the temporal detecting capability at this level. With the capabilities of being able to distinguish the timing differences in the millisecond scale, echo-shifted InI could be a useful fMRI tool for obtaining temporal information at a time scale closer to that of neuronal dynamics.

Neuronal mechanisms of auditory distance perception are poorly understood, largely because contributions of intensity and distance processing are difficult to differentiate. Typically, the received intensity increases when sound sources approach us. However, we can also distinguish between soft-but-nearby and loud-but-distant sounds, indicating that distance processing can also be based on intensity-independent cues. Here, we combined behavioral experiments, fMRI measurements, and computational analyses to identify the neural representation of distance independent of intensity. In a virtual reverberant environment, we simulated sound sources at varying distances (15–100 cm) along the right-side interaural axis. Our acoustic analysis suggested that, of the individual intensity-independent depth cues available for these stimuli, direct-to-reverberant ratio (D/R) is more reliable and robust than interaural level difference (ILD). However, on the basis of our behavioral results, subjects’ discrimination performance was more consistent with complex intensity-independent distance representations, combining both available cues, than with representations on the basis of either D/R or ILD individually. fMRI activations to sounds varying in distance (containing all cues, including intensity), compared with activations to sounds varying in intensity only, were significantly increased in the planum temporale and posterior superior temporal gyrus contralateral to the direction of stimulation. This fMRI result suggests that neurons in posterior nonprimary auditory cortices, in or near the areas processing other auditory spatial features, are sensitive to intensity-independent sound properties relevant for auditory distance perception.

Naturalistic stimuli such as movies are increasingly used to engage cognitive and emotional processes during fMRI of brain hemodynamic activity. However, movies have been little utilized during magnetoencephalography (MEG) and EEG that directly measure population-level neuronal activity at a millisecond resolution. Here, subjects watched a 17-min segment from the movie Crash (Lionsgate Films, 2004) twice during simultaneous MEG/EEG recordings. Physiological noise components, including ocular and cardiac artifacts, were removed using the DRIFTER algorithm. Dynamic estimates of cortical activity were calculated using MRI-informed minimum-norm estimation. To improve the signal-to-noise ratio (SNR), principal component analyses (PCA) were employed to extract the prevailing temporal characteristics within each anatomical parcel of the Freesurfer Desikan-Killiany cortical atlas. A variety of alternative inter-subject correlation (ISC) approaches were then utilized to investigate the reliability of inter-subject synchronization during natural viewing. In the first analysis, the ISCs of the time series of each anatomical region over the full time period across all subject pairs were calculated and averaged. In the second analysis, dynamic ISC (dISC) analysis, the correlation was calculated over a sliding window of 200 ms with 3.3 ms steps. Finally, in a between-run ISC analysis, the between-run correlation was calculated over the dynamic ISCs of the two different runs after the Fisher z-transformation. Overall, the most reliable activations occurred in occipital/inferior temporal visual and superior temporal auditory cortices as well as in the posterior cingulate, precuneus, pre- and post-central gyri, and right inferior and middle frontal gyri. Significant between-run ISCs were observed in superior temporal auditory cortices and inferior temporal visual cortices. Taken together, our results show that movies can be utilized as naturalistic stimuli in MEG/EEG similarly as in fMRI studies.

When multiple persons speak simultaneously, it may be difficult for the listener to direct attention to correct sound objects among conflicting ones. This could occur, for example, in an emergency situation in which one hears conflicting instructions and the loudest, instead of the wisest, voice prevails. Here, we used cortically-constrained oscillatory MEG/EEG estimates to examine how different brain regions, including caudal anterior cingulate (cACC) and dorsolateral prefrontal cortices (DLPFC), work together to resolve these kinds of auditory conflicts. During an auditory flanker interference task, subjects were presented with sound patterns consisting of three different voices, from three different directions (45° left, straight ahead, 45° right), sounding out either the letters “A” or “O”. They were asked to discriminate which sound was presented centrally and ignore the flanking distracters that were phonetically either congruent (50%) or incongruent (50%) with the target. Our cortical MEG/EEG oscillatory estimates demonstrated a direct relationship between performance and brain activity, showing that efficient conflict resolution, as measured with reduced conflict-induced RT lags, is predicted by theta/alpha phase coupling between cACC and right lateral frontal cortex regions intersecting the right frontal eye fields (FEF) and DLPFC, as well as by increased pre-stimulus gamma (60–110 Hz) power in the left inferior fontal cortex. Notably, cACC connectivity patterns that correlated with behavioral conflict-resolution measures were found during both the pre-stimulus and the pre-response periods. Our data provide evidence that, instead of being only transiently activated upon conflict detection, cACC is involved in sustained engagement of attentional resources required for effective sound object selection performance., National Institutes of Health (U.S.) (Award R01MH083744), National Institutes of Health (U.S.) (Award R21DC010060), National Institutes of Health (U.S.) (Award R21DC014134), National Institutes of Health (U.S.) (Award R01HD040712), National Institutes of Health (U.S.) (Award R01NS037462), National Institutes of Health (U.S.) (Award 5R01EB009048), Athinoula A. Martinos Center for Biomedical Imaging. Center for Functional Neuroimaging Technologies (P41EB015896), National Institute for Biomedical Imaging and Bioengineering (U.S.) (P41 Biotechnology Resource Grant), National Center for Research Resources (U.S.) (Shared Instrumentation Grant S10RR014978), National Center for Research Resources (U.S.) (Shared Instrumentation Grant S10RR021110), National Center for Research Resources (U.S.) (Shared Instrumentation Grant S10RR019307), National Center for Research Resources (U.S.) (Shared Instrumentation Grant S10RR014798), National Center for Research Resources (U.S.) (Shared Instrumentation Grant S10RR023401)

Neurophysiological animal models suggest that anterior auditory cortex (AC) areas process sound identity information, whereas posterior ACs specialize in sound location processing. In humans, inconsistent neuroimaging results and insufficient causal evidence have challenged the existence of such parallel AC organization. Here we transiently inhibit bilateral anterior or posterior AC areas using MRI-guided paired-pulse transcranial magnetic stimulation (TMS) while subjects listen to Reference/Probe sound pairs and perform either sound location or identity discrimination tasks. The targeting of TMS pulses, delivered 55–145 ms after Probes, is confirmed with individual-level cortical electric-field estimates. Our data show that TMS to posterior AC regions delays reaction times (RT) significantly more during sound location than identity discrimination, whereas TMS to anterior AC regions delays RTs significantly more during sound identity than location discrimination. This double dissociation provides direct causal support for parallel processing of sound identity features in anterior AC and sound location in posterior AC. Observational imaging studies in humans have suggested that sound identification and localization occur in the same region of the auditory cortex. Ahveninen et al. now show that sound identity and location are processed in anterior and posterior regions, respectively, of the auditory cortex.

In everyday listening situations, we need to constantly switch between alternative sound sources and engage attention according to cues that match our goals and expectations. The exact neuronal bases of these processes are poorly understood. We investigated oscillatory brain networks controlling auditory attention using cortically constrained fMRI-weighted magnetoencephalography/EEG source estimates. During consecutive trials, participants were instructed to shift attention based on a cue, presented in the ear where a target was likely to follow. To promote audiospatial attention effects, the targets were embedded in streams of dichotically presented standard tones. Occasionally, an unexpected novel sound occurred opposite to the cued ear to trigger involuntary orienting. According to our cortical power correlation analyses, increased frontoparietal/temporal 30–100 Hz gamma activity at 200–1400 msec after cued orienting predicted fast and accurate discrimination of subsequent targets. This sustained correlation effect, possibly reflecting voluntary engagement of attention after the initial cue-driven orienting, spread from the TPJ, anterior insula, and inferior frontal cortices to the right FEFs. Engagement of attention to one ear resulted in a significantly stronger increase of 7.5–15 Hz alpha in the ipsilateral than contralateral parieto-occipital cortices 200–600 msec after the cue onset, possibly reflecting cross-modal modulation of the dorsal visual pathway during audiospatial attention. Comparisons of cortical power patterns also revealed significant increases of sustained right medial frontal cortex theta power, right dorsolateral pFC and anterior insula/inferior frontal cortex beta power, and medial parietal cortex and posterior cingulate cortex gamma activity after cued versus novelty-triggered orienting (600–1400 msec). Our results reveal sustained oscillatory patterns associated with voluntary engagement of auditory spatial attention, with the frontoparietal and temporal gamma increases being best predictors of subsequent behavioral performance.

Auditory attention and working memory (WM) allow for selection and maintenance of relevant sound information in our minds, respectively, thus underlying goal-directed functioning in everyday acoustic environments. It is still unclear whether these two closely coupled functions are based on a common neural circuit, or whether they involve genuinely distinct subfunctions with separate neuronal substrates. In a full factorial functional MRI (fMRI) design, we independently manipulated the levels of auditory-verbal WM load and attentional interference using modified Auditory Continuous Performance Tests. Although many frontoparietal regions were jointly activated by increases of WM load and interference, there was a double dissociation between prefrontal cortex (PFC) subareas associated selectively with either auditory attention or WM. Specifically, anterior dorsolateral PFC (DLPFC) and the right anterior insula were selectively activated by increasing WM load, whereas subregions of middle lateral PFC and inferior frontal cortex (IFC) were associated with interference only. Meanwhile, a superadditive interaction between interference and load was detected in left medial superior frontal cortex, suggesting that in this area, activations are not only overlapping, but reflect a common resource pool recruited by increased attentional and WM demands. Indices of WM-specific suppression of anterolateral non-primary auditory cortices (AC) and attention-specific suppression of primary AC were also found, possibly reflecting suppression/interruption of sound-object processing of irrelevant stimuli during continuous task performance. Our results suggest a double dissociation between auditory attention and working memory in subregions of anterior DLPFC vs. middle lateral PFC/IFC in humans, respectively, in the context of substantially overlapping circuits.

In everyday life, we need a capacity to flexibly shift attention between alternative sound sources. However, relatively little work has been done to elucidate the mechanisms of attention shifting in the auditory domain. Here, we used a mixed event-related/sparse-sampling fMRI approach to investigate this essential cognitive function. In each 10-sec trial, subjects were instructed to wait for an auditory "cue" signaling the location where a subsequent "target" sound was likely to be presented. The target was occasionally replaced by an unexpected "novel" sound in the uncued ear, to trigger involuntary attention shifting. To maximize the attention effects, cues, targets, and novels were embedded within dichotic 800-Hz vs. 1500-Hz pure-tone "standard" trains. The sound of clustered fMRI acquisition (starting at t = 7.82 sec) served as a controlled trial-end signal. Our approach revealed notable activation differences between the conditions. Cued voluntary attention shifting activated the superior intra--parietal sulcus (IPS), whereas novelty-triggered involuntary orienting activated the inferior IPS and certain subareas of the precuneus. Clearly more widespread activations were observed during voluntary than involuntary orienting in the premotor cortex, including the frontal eye fields. Moreover, we found -evidence for a frontoinsular-cingular attentional control network, consisting of the anterior insula, inferior frontal cortex, and medial frontal cortices, which were activated during both target discrimination and voluntary attention shifting. Finally, novels and targets activated much wider areas of superior temporal auditory cortices than shifting cues.

How can we concentrate on relevant sounds in noisy environments? A “gain model” suggests that auditory attention simply amplifies relevant and suppresses irrelevant afferent inputs. However, it is unclear whether this suffices when attended and ignored features overlap to stimulate the same neuronal receptive fields. A “tuning model” suggests that, in addition to gain, attention modulates feature selectivity of auditory neurons. We recorded magnetoencephalography, EEG, and functional MRI (fMRI) while subjects attended to tones delivered to one ear and ignored opposite-ear inputs. The attended ear was switched every 30 s to quantify how quickly the effects evolve. To produce overlapping inputs, the tones were presented alone vs. during white-noise masking notch-filtered ±1/6 octaves around the tone center frequencies. Amplitude modulation (39 vs. 41 Hz in opposite ears) was applied for “frequency tagging” of attention effects on maskers. Noise masking reduced early (50–150 ms; N1) auditory responses to unattended tones. In support of the tuning model, selective attention canceled out this attenuating effect but did not modulate the gain of 50–150 ms activity to nonmasked tones or steady-state responses to the maskers themselves. These tuning effects originated at nonprimary auditory cortices, purportedly occupied by neurons that, without attention, have wider frequency tuning than ±1/6 octaves. The attentional tuning evolved rapidly, during the first few seconds after attention switching, and correlated with behavioral discrimination performance. In conclusion, a simple gain model alone cannot explain auditory selective attention. In nonprimary auditory cortices, attention-driven short-term plasticity retunes neurons to segregate relevant sounds from noise.