Individual differences in associative memory among older adults explained by hippocampal subfield structure and function.

Older adults experience impairments in episodic memory, ranging from mild to clinically significant. Given the critical role of the medial temporal lobe (MTL) in episodic memory, age-related changes in MTL structure and function may partially account for individual differences in memory. Using ultra-high-field 7T structural MRI and high-resolution 3T functional MRI (hr-fMRI), we evaluated MTL subfield thickness and function in older adults representing a spectrum of cognitive health. Participants performed an associative memory task during hr-fMRI in which they encoded and later retrieved face-name pairs. Motivated by prior research, we hypothesized that differences in performance would be explained by the following: (i) entorhinal cortex (ERC) and CA1 apical neuropil layer [CA1-stratum radiatum lacunosum moleculare (SRLM)] thickness, and (ii) activity in ERC and the dentate gyrus (DG)/CA3 region. Regression analyses revealed that this combination of factors significantly accounted for variability in memory performance. Among these metrics, CA1-SRLM thickness was positively associated with memory, whereas DG/CA3 retrieval activity was negatively associated with memory. Furthermore, including structural and functional metrics in the same model better accounted for performance than did single-modality models. These results advance the understanding of how independent but converging influences of both MTL subfield structure and function contribute to age-related memory impairment, complementing findings in the rodent and human postmortem literatures.

A harmonized segmentation protocol for hippocampal and parahippocampal subregions: Why do we need one and what are the key goals?

The advent of high-resolution magnetic resonance imaging (MRI) has enabled in vivo research in a variety of populations and diseases on the structure and function of hippocampal subfields and subdivisions of the parahippocampal gyrus. Because of the many extant and highly discrepant segmentation protocols, comparing results across studies is difficult. To overcome this barrier, the Hippocampal Subfields Group was formed as an international collaboration with the aim of developing a harmonized protocol for manual segmentation of hippocampal and parahippocampal subregions on high-resolution MRI. In this commentary we discuss the goals for this protocol and the associated key challenges involved in its development. These include differences among existing anatomical reference materials, striking the right balance between reliability of measurements and anatomical validity, and the development of a versatile protocol that can be adopted for the study of populations varying in age and health. The commentary outlines these key challenges, as well as the proposed solution of each, with concrete examples from our working plan. Finally, with two examples, we illustrate how the harmonized protocol, once completed, is expected to impact the field by producing measurements that are quantitatively comparable across labs and by facilitating the synthesis of findings across different studies. © 2016 Wiley Periodicals, Inc.

Quantitative comparison of 21 protocols for labeling hippocampal subfields and parahippocampal subregions in in vivo MRI: towards a harmonized segmentation protocol.

OBJECTIVE: An increasing number of human in vivo magnetic resonance imaging (MRI) studies have focused on examining the structure and function of the subfields of the hippocampal formation (the dentate gyrus, CA fields 1-3, and the subiculum) and subregions of the parahippocampal gyrus (entorhinal, perirhinal, and parahippocampal cortices). The ability to interpret the results of such studies and to relate them to each other would be improved if a common standard existed for labeling hippocampal subfields and parahippocampal subregions. Currently, research groups label different subsets of structures and use different rules, landmarks, and cues to define their anatomical extents. This paper characterizes, both qualitatively and quantitatively, the variability in the existing manual segmentation protocols for labeling hippocampal and parahippocampal substructures in MRI, with the goal of guiding subsequent work on developing a harmonized substructure segmentation protocol. METHOD: MRI scans of a single healthy adult human subject were acquired both at 3 T and 7 T. Representatives from 21 research groups applied their respective manual segmentation protocols to the MRI modalities of their choice. The resulting set of 21 segmentations was analyzed in a common anatomical space to quantify similarity and identify areas of agreement. RESULTS: The differences between the 21 protocols include the region within which segmentation is performed, the set of anatomical labels used, and the extents of specific anatomical labels. The greatest overall disagreement among the protocols is at the CA1/subiculum boundary, and disagreement across all structures is greatest in the anterior portion of the hippocampal formation relative to the body and tail. CONCLUSIONS: The combined examination of the 21 protocols in the same dataset suggests possible strategies towards developing a harmonized subfield segmentation protocol and facilitates comparison between published studies.

Shared vulnerability of two synaptically-connected medial temporal lobe areas to age and cognitive decline: a seven tesla magnetic resonance imaging study.

The medial temporal lobe (MTL) is the first brain area to succumb to neurofibrillary tau pathology in Alzheimer's disease (AD). Postmortem human tissue evaluation suggests that this pathology propagates in an ordered manner, with the entorhinal cortex (ERC) and then CA1 stratum radiatum and stratum lacunosum-moleculare (CA1-SRLM)--two monosynaptically connected structures--exhibiting selective damage. Here, we hypothesized that, if ERC and CA1-SRLM share an early vulnerability to AD pathology, then atrophy should occur in a proportional manner between the two structures. We tested this hypothesis in living humans, using ultra-high field 7.0 T MRI to make fine measurements of MTL microstructure. Among a pool of age-matched healthy controls and patients with amnestic mild cognitive impairment and mild AD, we found a significant correlation between ERC and CA1-SRLM size that could not be explained by global atrophy affecting the MTL. Of the various structures that contribute axons or dendrites into the CA1-SRLM neuropil, only ERC emerged as a significant predictor of CA1-SRLM size in a linear regression analysis. In contrast, other synaptically connected elements of the MTL did not exhibit size correlations. CA1-SRLM and ERC structural covariance was significant for older controls and not patients, whereas the opposite pattern emerged for a correlation between CA1-SRLM and episodic memory performance. Interestingly, CA1-SRLM and ERC were the only MTL structures to atrophy in older controls relative to a younger comparison group. Together, these findings suggest that ERC and CA1-SRLM share vulnerability to both age and AD-associated atrophy.

Reducing Risks of Facial Scarring.

Risk factors for the formation of facial scars include skin type, ethnicity, scar location, and certain medical conditions that contribute to poor or delayed healing. Risk of scar can be reduced with appropriate surgical planning, including proper placement and design of incisions, meticulous skin closure, aseptic technique, and wound care to improve healing. Common pathologic scars include hypertrophic scars and keloid scars, each of which has unique approaches to surgical revision and medical treatment due to their respective risks of recurrence. Topical scar therapies, medical therapies, and surgical revision techniques for improvement in final scar appearance are discussed.

Extensive Tongue Laceration in an Edentulous Infant: Is It Child Abuse?

It is important for medical providers to distinguish between accidental and abusive mechanisms of injury in children. In the absence of a serious trauma, an isolated tongue laceration and oromaxillofacial trauma in a young, edentulous infant raises significant concern for abuse. The presented case demonstrates a unique injury pattern and serves as an opportunity to explore the multidisciplinary approach to infant trauma in Otolaryngology. Presented is an edentulous infant who sustained a deep splitting laceration of the oral tongue as a result of being dropped a short distance onto carpeted floor. This injury pattern, in the absence of other trauma, raised concern for abuse. Hospital social work and Child Abuse Pediatrics further investigated the matter. A surveillance camera video was produced which demonstrated the blunt force of the fall, coupled with the friction sliding on the floor, ripped open the infant's tongue and left a pattern otherwise suspicious for sharp object laceration. To our knowledge, this is the first report describing a full-thickness tongue laceration after a fall from a caregiver's arms onto carpeted ground. This case underscores the responsibility of the astute provider coupled with a multidisciplinary team to identify or rule out potential child abuse.

Steroid-eluting Stent Placement for Refractory Stenosis of Parotid Megaduct After Sialodochoplasty.

Salivary megaduct with stricture is characterized by recurrent pain, swelling, and infection, leading to reduced quality of life. Surgical management includes sialodochoplasty, however, recurrence is common and repeated surgery can lead to further scarring. In the sinuses, drug-eluting stents (DES) are used to reduce scarring after surgery, yet no such technology exists for salivary megaduct with stricture.We trialed DES for this condition with promising results which may pave the way for future development.

COVID-19 and the Otolaryngology Residency Match: Rising Incidence of Home Matches.

OBJECTIVES/HYPOTHESIS: To quantify the effect of the coronavirus disease 2019 (COVID-19) pandemic upon the 2020 to 2021 residency match for Otolaryngology-Head and Neck Surgery (OHNS). STUDY DESIGN: Retrospective cohort design. METHODS: Residency match outcomes for all applicants to our institution during 2020 to 2021 were collected from the National Residency Matching Program including medical school of origin and matched program. Matches were categorized as to home-program, within-region, or out-of-region and sorted by US geographic region. Matches from the 2020 to 2021 cycle were compared to those from 2019 to 2020, as well as averages and trends from match cycles 2016 to 2020. Statistical analysis included descriptive statistics and chi-square testing. RESULTS: During 2020 to 2021, there were 436 applicants to our single OHNS program. From 2019-2020 to 2020-2021, the match rate decreased significantly for groups studied, including: All applicants (72.0% [268/372] to 64.7% [282/436]; P = .025); all US MD Senior applicants (76.5% [254/332] to 68.9% [262/380]; P = .024); and US MD Seniors specifically without a home program (77.5% [31/40] to 56.4% [22/39]; P = .046). The match rate for US MD Seniors with a home program did not change significantly (76.4% [223/292] to 70.4% [240/341]; P = .09). From 2019-2020 to 2020-2021, the proportion of US MD seniors who matched to home-program increased significantly (22.0% [49/223] to 30.0% [72/240]; P = .05). CONCLUSION: The COVID-19 pandemic saw high volumes of OHNS applicants with an overall decreased rate of matching compared to previous years. These changes particularly affected applicants without home programs. Home-program matching increased significantly, likely as a consequence of the limitations placed on in-person away experiences including interviews. Laryngoscope, 132:1934-1938, 2022.

Surgical wound classification in otolaryngology: A state-of-the-art review.

Objective: To describe the issues related to the assignment of surgical wound classification as it pertains to Otolaryngology-Head & Neck surgery, and to present a simple framework by which providers can assign wound classification. Data Sources: Literature review. Conclusion: Surgical wound classification in its current state is limited in its utility. It has recently been disregarded by major risk assessment models, likely due to inaccurate and inconsistent reporting by providers and operative staff. However, if data accuracy is improved, this metric may be useful to inform the risk of surgical site infection. In an era of quality-driven care and reimbursement, surgical wound classification may become an equally important indicator of quality.

Surgical ergonomics: Assessment of surgeon posture and impact of training device during otolaryngology procedures.

Objective: To identify factors associated with cervical-thoracic spine posture in otolaryngology surgeries and evaluate the efficacy of a commercially available posture-training device in enhancing surgeon ergonomics. Methods: Over 3 months, neck and spine posture from individuals performing otolaryngology surgeries was recorded using UpRight Go 2™. Average baseline posture was first recorded and biofeedback was later introduced to attempt to correct posture. The proportion of time spent in upright/neutral cervical-thoracic spine posture was correlated with surgeon and procedure characteristics and compared to proportion of upright posture time after biofeedback intervention. Results: The proportion of upright operating time was significantly different between procedure subtypes and surgical approaches with best performance in rhinology procedures and worst performance in head and neck surgeries (90% vs. 62%; both p < .001). Female gender, shorter stature, and use of sitting stools were associated with greater proportion of surgery spent upright (all p < .05). Loupes use was associated with less time in upright posture (p < .001). With biofeedback intervention, 8 of 10 subjects demonstrated an average of 5% improvement in operating upright, with most improvement found when performing laryngology procedures (7%) and least improvement in head and neck procedures (2%). Conclusions: While surgeon posture varies across otolaryngology surgeries, sitting and minimizing the use of loupes may help promote a more ergonomic operating environment and improve surgeon posture. Although the efficacy of biofeedback intervention from a commercially available posture-training device differs among otolaryngologists, exploration of alternative interventions and incorporation of an ergonomics curriculum is warranted to address postural issues experienced by many surgeons. Level of Evidence: 3.

Geographic Trends in the Otolaryngology Match (2016-2020).

OBJECTIVE: Presenting geographic matching trends over 5 match cycles (2016-2020) to serve as a context for changes in residency match outcomes due to the coronavirus disease 2019 (COVID-19) pandemic. STUDY DESIGN: Retrospective review. SETTING: Single academic institution-affiliated otolaryngology-head and neck surgery residency program. METHODS: Residency match outcomes for all applicants to our institution (2015-2019) were collected from the National Residency Matching Program, including medical school and matched program. Matches were categorized as home program, home region, or out of region and sorted by US geographic region. Statistical analysis included frequencies, totals, χ2 testing, and binary logistic regression. RESULTS: From 2016 to 2020, the US MD senior match rate was 84.9%: 18.9% to home programs, 35.7% to home region, and 45.3% to out of region. Rates were similar across regions and decreased over time. Westerners matched to home programs more than Southerners or Midwesterners (27.5% vs 16.0% and 16.0%, P < .01). Southerners and Westerners were more likely to match within their regions (South: 63.1%, P = .011, odds ratio [OR] = 1.296, 95% CI, 1.060-1.584; West: 42.0%, P = .018, OR = 1.462, 95% CI, 1.066-2.004). Matching from out of region was more likely in the West and less likely in the South (West: 58.0%, P = .017, OR = 1.379, 95% CI, 1.059-1.796; South: 36.9%, P < .001, OR = 0.584, 95% CI, 0.47-0.727). CONCLUSION: From 2016 to 2020 in otolaryngology-head and neck surgery, about 1 in 5 matches were to home institutions, a trend that appeared to be more common in the West. Over 4 out of 5 trainees match to nonhome programs, and nearly half relocate to a new region for training. Changes to travel, rotations, and interviews due to COVID-19 may influence these trends.

A virtual sub-internship for otolaryngology-head and neck surgery.

OBJECTIVE: During the COVID-19 pandemic, away rotations were suspended for safety purposes. This led to the development of online interactive learning modules for students, now known as virtual sub-internships (VSIs). To date, VSIs within otolaryngology-head and neck surgery (OHNS) have been limited in their description and design. STUDY DESIGN: Cross-sectional survey. SETTING: ACGME-accredited OHNS residency program. METHODS: Our curriculum for an OHNS VSI is presented. Based on the model used by our OHNS residency program, the VSI consisted of a 2-week block of activities and interactive small-group discussions. A post-VSI feedback survey was distributed to participants; results are reported. RESULTS: Six 2-week VSI sessions were administered. Twenty-one individuals participated from all US regions, median 4 individuals per session. Fifteen participants (71.4%) completed the feedback survey. Of survey respondents, 20% lacked a home OHNS residency program, and no respondents' home-programs featured a VSI. All respondents were satisfied with the schedule and organization of the VSI, and 73.3% (11 of 15) felt it was of appropriate duration. All respondents reported a high degree of familiarity with the program, with a greater (86.7%) or equal (13.3%) level of interest in applying to the residency program as a result of participating in the VSI. CONCLUSION: This VSI curriculum offers a well-received virtual learning experience for medical students applying to OHNS residency. It provides an opportunity for programs to expand their appeal to potential applicants who may otherwise be restricted in their ability to travel.

Association of Sinonasal Inflammation With Functional Brain Connectivity.

Importance: In recent years, there have been several meaningful advances in the understanding of the cognitive effects of chronic rhinosinusitis. However, an investigation exploring the potential link between the underlying inflammatory disease and higher-order neural processing has not yet been performed. Objective: To describe the association of sinonasal inflammation with functional brain connectivity (Fc), which may underlie chronic rhinosinusitis-related cognitive changes. Design, Setting, and Participants: This is a case-control study using the Human Connectome Project (Washington University-University of Minnesota Consortium of the Human Connectome Project 1200 release), an open-access and publicly available data set that includes demographic, imaging, and behavioral data for 1206 healthy adults aged 22 to 35 years. Twenty-two participants demonstrated sinonasal inflammation (Lund-Mackay score [LMS] ≥ 10) and were compared with age-matched and sex-matched healthy controls (LMS = 0). These participants were further stratified into moderate (LMS < 14, n = 13) and severe (LMS ≥ 14, n = 9) inflammation groups. Participants were screened and excluded if they had a history of psychiatric disorder and/or neurological or genetic diseases. Participants with diabetes or cardiovascular disease were also excluded, as these conditions may affect neuroimaging quality. The data were accessed between October 2019 and August 2020. Data analysis was performed between May 2020 and August 2020. Main Outcomes and Measures: The primary outcome was the difference in resting state Fc within and between the default mode, frontoparietal, salience, and dorsal attention brain networks. Secondary outcomes included assessments of cognitive function using the National Institutes of Health Toolbox Cognition Battery. Results: A total of 22 patients with chronic rhinosinusitis and 22 healthy controls (2 [5%] were aged 22-25 years, 26 [59%] were aged 26-30 years, and 16 [36%] were aged 31-35 years; 30 [68%] were men) were included in the analysis. Participants with sinonasal inflammation showed decreased Fc within the frontoparietal network, in a region involving bilateral frontal medial cortices. This region demonstrated increased Fc to 2 nodes within the default-mode network and decreased Fc to 1 node within the salience network. The magnitude of these differences increased with inflammation severity (dose dependent). There were no significant associations seen on cognitive testing. Conclusions and Relevance: In this case-control study, participants with sinonasal inflammation showed decreased brain connectivity within a major functional hub with a central role in modulating cognition. This region also shows increased connectivity to areas that are activated during introspective and self-referential processing and decreased connectivity to areas involved in detection and response to stimuli. Future prospective studies are warranted to determine the applicability of these findings to a clinical chronic rhinosinusitis population.

Association of CSF Biomarkers With Hippocampal-Dependent Memory in Preclinical Alzheimer Disease.

OBJECTIVE: To determine whether memory tasks with demonstrated sensitivity to hippocampal function can detect variance related to preclinical Alzheimer disease (AD) biomarkers, we examined associations between performance in 3 memory tasks and CSF ß-amyloid (Aß)42/Aß40 and phosopho-tau181 (p-tau181) in cognitively unimpaired older adults (CU). METHODS: CU enrolled in the Stanford Aging and Memory Study (n = 153; age 68.78 ± 5.81 years; 94 female) completed a lumbar puncture and memory assessments. CSF Aß42, Aß40, and p-tau181 were measured with the automated Lumipulse G system in a single-batch analysis. Episodic memory was assayed using a standardized delayed recall composite, paired associate (word-picture) cued recall, and a mnemonic discrimination task that involves discrimination between studied "target" objects, novel "foil" objects, and perceptually similar "lure" objects. Analyses examined cross-sectional relationships among memory performance, age, and CSF measures, controlling for sex and education. RESULTS: Age and lower Aß42/Aß40 were independently associated with elevated p-tau181. Age, Aß42/Aß40, and p-tau181 were each associated with (1) poorer associative memory and (2) diminished improvement in mnemonic discrimination performance across levels of decreased task difficulty (i.e., target-lure similarity). P-tau mediated the effect of Aß42/Aß40 on memory. Relationships between CSF proteins and delayed recall were similar but nonsignificant. CSF Aß42 was not significantly associated with p-tau181 or memory. CONCLUSIONS: Tests designed to tax hippocampal function are sensitive to subtle individual differences in memory among CU and correlate with early AD-associated biomarker changes in CSF. These tests may offer utility for identifying CU with preclinical AD pathology.

Substantia Nigra Volume Dissociates Bradykinesia and Rigidity from Tremor in Parkinson's Disease: A 7 Tesla Imaging Study.

BACKGROUND: In postmortem analysis of late stage Parkinson's disease (PD) neuronal loss in the substantial nigra (SN) correlates with the antemortem severity of bradykinesia and rigidity, but not tremor. OBJECTIVE: To investigate the relationship between midbrain nuclei volume as an in vivo biomarker for surviving neurons in mild-to-moderate patients using 7.0 Tesla MRI. METHODS: We performed ultra-high resolution quantitative susceptibility mapping (QSM) on the midbrain in 32 PD participants with less than 10 years duration and 8 healthy controls. Following blinded manual segmentation, the individual volumes of the SN, subthalamic nucleus, and red nucleus were measured. We then determined the associations between the midbrain nuclei and clinical metrics (age, disease duration, MDS-UPDRS motor score, and subscores for bradykinesia/rigidity, tremor, and postural instability/gait difficulty). RESULTS: We found that smaller SN correlated with longer disease duration (r = -0.49, p = 0.004), more severe MDS-UPDRS motor score (r = -0.42, p = 0.016), and more severe bradykinesia-rigidity subscore (r = -0.47, p = 0.007), but not tremor or postural instability/gait difficulty subscores. In a hemi-body analysis, bradykinesia-rigidity severity only correlated with SN contralateral to the less-affected hemi-body, and not contralateral to the more-affected hemi-body, possibly reflecting the greatest change in dopamine neuron loss early in disease. Multivariate generalized estimating equation model confirmed that bradykinesia-rigidity severity, age, and disease duration, but not tremor severity, predicted SN volume. CONCLUSIONS: In mild-to-moderate PD, SN volume relates to motor manifestations in a motor domain-specific and laterality-dependent manner. Non-invasive in vivo 7.0 Tesla QSM may serve as a biomarker in longitudinal studies of SN atrophy and in studies of people at risk for developing PD.

Hippocampal and cortical mechanisms at retrieval explain variability in episodic remembering in older adults.

Age-related episodic memory decline is characterized by striking heterogeneity across individuals. Hippocampal pattern completion is a fundamental process supporting episodic memory. Yet, the degree to which this mechanism is impaired with age, and contributes to variability in episodic memory, remains unclear. We combine univariate and multivariate analyses of fMRI data from a large cohort of cognitively normal older adults (N=100) to measure hippocampal activity and cortical reinstatement during retrieval of trial-unique associations. Trial-wise analyses revealed that (a) hippocampal activity scaled with reinstatement strength, (b) cortical reinstatement partially mediated the relationship between hippocampal activity and associative retrieval, (c) older age weakened cortical reinstatement and its relationship to memory behaviour. Moreover, individual differences in the strength of hippocampal activity and cortical reinstatement explained unique variance in performance across multiple assays of episodic memory. These results indicate that fMRI indices of hippocampal pattern completion explain within- and across-individual memory variability in older adults.

Hippocampal CA1 subfield predicts episodic memory impairment in Parkinson's disease.

OBJECTIVE: Parkinson's disease (PD) episodic memory impairments are common; however, it is not known whether these impairments are due to hippocampal pathology. Hippocampal Lewy-bodies emerge by Braak stage 4, but are not uniformly distributed. For instance, hippocampal CA1 Lewy-body pathology has been specifically associated with pre-mortem episodic memory performance in demented patients. By contrast, the dentate gyrus (DG) is relatively free of Lewy-body pathology. In this study, we used ultra-high field 7-Tesla to measure hippocampal subfields in vivo and determine if these measures predict episodic memory impairment in PD during life. METHODS: We studied 29 participants with PD (age 65.5 ±â€¯7.8 years; disease duration 4.5 ±â€¯3.0 years) and 8 matched-healthy controls (age 67.9 ±â€¯6.8 years), who completed comprehensive neuropsychological testing and MRI. With 7-Tesla MRI, we used validated segmentation techniques to estimate CA1 stratum pyramidale (CA1-SP) and stratum radiatum lacunosum moleculare (CA1-SRLM) thickness, dentate gyrus/CA3 (DG/CA3) area, and whole hippocampus area. We used linear regression, which included imaging and clinical measures (age, duration, education, gender, and CSF), to determine the best predictors of episodic memory impairment in PD. RESULTS: In our cohort, 62.1% of participants with PD had normal cognition, 27.6% had mild cognitive impairment, and 10.3% had dementia. Using 7-Tesla MRI, we found that smaller CA1-SP thickness was significantly associated with poorer immediate memory, delayed memory, and delayed cued memory; by contrast, whole hippocampus area, DG/CA3 area, and CA1-SRLM thickness did not significantly predict memory. Age-adjusted linear regression models revealed that CA1-SP predicted immediate memory (beta[standard error]10.895[4.215], p < .05), delayed memory (12.740[5.014], p < .05), and delayed cued memory (12.801[3.991], p < .05). In the fully-adjusted models, which included all five clinical measures as covariates, only CA1-SP remained a significant predictor of delayed cued memory (13.436[4.651], p < .05). CONCLUSIONS: In PD, we found hippocampal CA1-SP subfield thickness estimated on 7-Tesla MRI scans was the best predictor of episodic memory impairment, even when controlling for confounding clinical measures. Our results imply that ultra-high field imaging could be a sensitive measure to identify changes in hippocampal subfields and thus probe the neuroanatomical underpinnings of episodic memory impairments in patients with PD.