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IntroductionLinking olfactory epithelium to the central nervous system are cranial nerve 1, the olfactory nerve, and cranial nerve “0,” and the nervus terminalis (NT). Since there is minimal expression of angiotensin-converting enzyme-2 (ACE-2) in the olfactory nerve, it is unclear how SARS-CoV-2 causes anosmia (loss of smell) and hypogeusia (reduction of taste). In animal models, NT expresses ACE-2 receptors, suggesting a possible SARS-CoV-2 viral entry site in humans. The purpose of this study was to determine whether ultra-high-field 7 T magnetic resonance imaging (MRI) could visualize the NT, olfactory bulbs (OB), and olfactory tract (OT) in healthy controls and COVID-19 anosmia or hypogeusia and to qualitatively assess for volume loss and T2 alterations.MethodsIn this study, 7 T MRI was used to evaluate the brain and olfactory regions in 45 COVID-19 patients and 29 healthy controls. Neuroimaging was qualitatively assessed by four board-certified neuroradiologists who were blinded to outcome assignments: for the presence or absence of NT; for OB, OT, and brain volume loss; and altered T2 signal, white matter T2 hyperintensities, microhemorrhages, enlarged perivascular spaces, and brainstem involvement.ResultsNT was identifiable in all COVID-19 patients and controls. T2 hyperintensity in the NT, OB, and OT in COVID-19 patients with anosmia or hypogeusia was statistically significant compared to controls and COVID-19 patients without anosmia or hypogeusia.DiscussionOn 7 T MRI, NT was radiographically identifiable, adjacent to OB and OT. In COVID-19 anosmia and hypogeusia, T2 hyperintensity of NT, OB, and OT was statistically significant compared to COVID-19 patients without anosmia or hypogeusia and controls. The NT may be a potential entry site for SARs-CoV-2 and may play a role in the pathophysiology of COVID-19 anosmia.

Background and purpose: Epilepsy is a complex neurological disorder affecting 50 million people worldwide. Persistent seizures may correlate with neural network, microstructural, and vascular changes within the thalamus. These thalamic changes may result from seizure activity or broader alterations involving neuronal vasculature and neuroinflammatory processes linked to glymphatic drainage. Improved resolution with Ultra-high field (UHF) magnetic resonance imaging (MRI) may be useful in identifying possible thalamic vascular abnormalities not otherwise detectable at lower field strengths. Materials and methods: We outline a novel method which leverages UHF neuroimaging for detection and quantification of vessels and perivascular spaces (PVS) within the thalamus in 25 epilepsy patients and 16 controls, to uncover possible underlying imaging biomarkers of epilepsy. In our analysis, we optimize a MATLAB-based Frangi-based detection tool called Perivascular Space Semi-Automated Segmentation (PVSSAS) to detect thalamic PVSs, and additionally use a second Frangi-based segmentation tool method to automate detection of vascular structures in the thalamus. The resulting PVS and vessel masks were used to quantify differences in the number of vessels, PVS, overlaps, and number of PVS overlaps per vessel detected between groups, using a Hessian detection filter linked on an 18-connected network. Results: We found significantly more thalamic PVS (p = 0.0307) and a significant increase in the number of thalamic vessels (p = 0.038) in patients compared to controls. Conclusion: Here we have developed a novel process which leverages UHF MRI to quantify and detect thalamic vessels and PVS that may provide a potential neuroimaging biomarker of epilepsy. Statement of Significance: We use 7T, ultra-high field MRI and employed an innovative combination of semi-automated perivascular space segmentation and automated vessel segmentation to visualize and quantify vessels and perivascular spaces (PVS) within the thalamus, a highly cited region of interest in epilepsy. To our knowledge, this is the first study to semi-automatically visualize and segment PVS in the thalamus and automatically detect thalamic vessels. We uncovered detectable differences in thalamic vasculature and PVS. These findings suggests that increases in the number of thalamic PVS and vessels may be a potential neuroimaging biomarker in epilepsy. This tool may be useful in the detection of subtle vascular changes in other regions of the brain related to epilepsy or can be employed in other neurological conditions.

Diffusion magnetic resonance imaging (dMRI) allows for a non-invasive visualization and quantitative assessment of white matter architecture in the brain by characterizing restrictions on the random motion of water molecules. Ultra-high field MRI scanners, such as those operating at 7 Tesla (7T) or higher, can boost the signal-to-noise ratio (SNR) to improve dMRI compared with what is attainable at conventional field strengths such as 3T or 1.5T. However, wavelength effects at 7T cause reduced transmit magnetic field efficiency in the human brain, mainly in the posterior fossa, manifesting as signal dropouts in this region. Recently, we reported a simple approach of using a wireless radiofrequency (RF) surface array to improve transmit efficiency and signal sensitivity at 7T. In this study, we demonstrate the feasibility and effectiveness of the RF enhancer in improving in vivo dMRI at 7T. The electromagnetic simulation results demonstrated a 2.1-fold increase in transmit efficiency with the use of the RF enhancer. The experimental results similarly showed a 1.9-fold improvement in transmit efficiency and a 1.4-fold increase in normalized SNR. These improvements effectively mitigated signal dropouts in regions with inherently lower SNR, such as the cerebellum, resulting in a better depiction of principal fiber orientations and an enhanced visualization of extended tracts.

American Academy of Pediatrics (AAP) recommendations for Autism Spectrum Disorder (ASD) screening do not specifically address safety-net clinics, which provide multidisciplinary healthcare services to underserved patients. This project explored the potential for ASD screening in safety-net clinics by assessing parental perceived knowledge of ASD at JayDoc Free Clinic, a student-run safety-net clinic in Wyandotte County, Kansas. May through December 2022, patients who reported to be the parent of a minor received a demographic survey and a Likert-style questionnaire assessing perceived knowledge of ASD, including understanding the importance of ASD screening and ASD signs and symptoms. Responses were categorized into positive, negative, and unsure. Demographic variables included the minor’s primary care provider (PCP) status. Results were analyzed using bivariate analysis, with chi-square tests for significance (p-value ≤ 0.05). Of the 52 participants who completed at least one Likert response, 55.8% reported their child had a PCP. Responses were somewhat balanced with 44.2% positive for understanding the importance of ASD screening and 53.8% positive for understanding ASD signs and symptoms. For understanding the signs and symptoms of ASD, an unsure response (32.7% of responses) was statistically associated with a lack of PCP (p = 0.017). The balance of positive with negative and unsure responses could reflect lack of ASD knowledge and may relate to healthcare inaccessibility. This is consistent with the significant association between lack of PCP and unsure responses for understanding ASD signs and symptoms. ASD screening and education in safety-net clinics like JayDoc could be valuable, particularly for children without a PCP.

Abstract Gulf War Illness is a chronic multi-symptom disorder with severe cognitive impairments which may be related to glutamate excitotoxicity and central nervous system dysfunction. The low glutamate diet has been proposed as a comprehensive intervention for Gulf War Illness. We examined the effects of the low glutamate diet on verbal working memory using a fMRI N-back task. Accuracy, whole-brain blood oxygen level dependency (BOLD) response, and task-based functional connectivity were assessed at baseline and after 1 month on the diet (N = 24). Multi-voxel pattern analysis identified regions of whole-brain BOLD pattern differences after the diet to be used as seeds for subsequent seed-to-voxel functional connectivity analyses. Verbal working memory accuracy improved after the diet (+ 13%; p = 0.006). Whole-brain BOLD signal changes were observed, revealing lower activation within regions of the frontoparietal network and default mode network after the low glutamate diet. Multi-voxel pattern analysis resulted in 3 clusters comprising parts of the frontoparietal network (clusters 1 and 2) and ventral attention network (cluster 3). The seed-to-voxel analyses identified significant functional connectivity changes post-diet for clusters 1 and 2 (peak p

Background: It is critical for patients seeking foot and ankle care to have access to quality online resources, as the treatment of their conditions may involve the use of a variety of diagnostic and therapeutic modalities with which they are unfamiliar. This study was performed to enhance our understanding of if and why patients use Internet-based educational materials, to identify trends in utilization, and to delineate the patient-perceived attributes of quality resources. Methods: Questionnaires were distributed to 150 adult foot and ankle patients. The questionnaire consisted of demographic and Internet utilization questions. Statistical analysis was performed to determine the frequency of responses for each question and the relationship between demographics and Internet usage. Results: Younger patients were more likely to use the Internet ( P = .006). However, there were no other significant differences in demographic attributes between patients who did (76%) and did not (24%) utilize the Internet ( P

Abstract Background People who inject drugs (PWID) suffer high morbidity and mortality from injection related infections (IRI). The inpatient setting is an ideal opportunity to treat underlying substance use disorder (SUD), but it is unclear how often this occurs. Objectives To quantify the utilization of behavioral health services for PWID during inpatient admissions for IRI. Methods Data for all hospital admissions in Florida in FY2017 were obtained from the Agency for Healthcare Administration. Hospitalization for IRI were obtained using a validated ICD-10 algorithm and treatment for substance use disorder was quantified using ICD-10-Procedure Coding System (ICD-10-PCS) codes. Result Among the 20,001 IRI admissions, there were 230 patients who received behavioral health services as defined by ICD-10-PCS SAT codes for treatment for SUD. Conclusions In a state with a large number of IRI, only a very small portion of admissions received behavioral health services. Increased efforts should be directed to studying referral patterns among physicians and other providers caring for this population and increasing utilization of behavioral health services.

While COVID-19 is primarily considered a respiratory disease, it has been shown to affect the central nervous system. Mounting evidence shows that COVID-19 is associated with neurological complications as well as effects thought to be related to neuroinflammatory processes. Due to the novelty of COVID-19, there is a need to better understand the possible long-term effects it may have on patients, particularly linkage to neuroinflammatory processes. Perivascular spaces (PVS) are small fluid-filled spaces in the brain that appear on MRI scans near blood vessels and are believed to play a role in modulation of the immune response, leukocyte trafficking, and glymphatic drainage. Some studies have suggested that increased number or presence of PVS could be considered a marker of increased blood-brain barrier permeability or dysfunction and may be involved in or precede cascades leading to neuroinflammatory processes. Due to their size, PVS are better detected on MRI at ultrahigh magnetic field strengths such as 7 Tesla, with improved sensitivity and resolution to quantify both concentration and size. As such, the objective of this prospective study was to leverage a semi-automated detection tool to identify and quantify differences in perivascular spaces between a group of 10 COVID-19 patients and a similar subset of controls to determine whether PVS might be biomarkers of COVID-19-mediated neuroinflammation. Results demonstrate a detectable difference in neuroinflammatory measures in the patient group compared to controls. PVS count and white matter volume were significantly different in the patient group compared to controls, yet there was no significant association between PVS count and symptom measures. Our findings suggest that the PVS count may be a viable marker for neuroinflammation in COVID-19, and other diseases which may be linked to neuroinflammatory processes.

Impairments in self-assessment in schizophrenia have been shown to have functional and clinical implications. Prior studies have suggested that overconfidence can be associated with poorer cognitive performance in people with schizophrenia, and that reduced awareness of performance may be associated with disability. However, overconfidence is common in healthy individuals as well. This study examines the correlations between performance on a social cognitive test, confidence in performance, effort allocated to the task, and correlates of confidence in patients with schizophrenia and healthy controls (HC). Measures included self-reports of depression, social cognitive ability, and social functioning. A performance-based emotion recognition test assessed social cognitive performance and provided the basis for confidence judgments. Although schizophrenia patients had reduced levels of overall confidence, there was a substantial subset of schizophrenic patients who manifested extreme overconfidence and these people had the poorest performance and reported the least depression. Further, a substantial number of HC over-estimated their performance as well. Patients with schizophrenia, in contrast to HC, did not adjust their effort to match task difficulty. Confidence was minimally related to task performance in patients but was associated with more rapid decisions in HC, across both correct and incorrect responses. Performance on social cognitive measures was minimally related to self-reports of social functioning in both samples. These data suggest global self-assessments are based on multiple factors, with confidence affecting self-assessments in the absence of feedback about performance. Keywords: Social cognition, Self-assessment, Social functioning, Schizophrenia, Confidence

Background: While metatarsus primus elevatus (MPE) has been implicated in the development of hallux rigidus, previous studies have presented conflicting findings regarding the relationship between MPE and arthritis. This may be due to the variety of definitions for MPE and the radiographic measurement techniques that are used to assess it. Additionally, previous studies have only assessed elevation of the first metatarsal with respect to the floor or the second metatarsal, and not with respect to the proximal phalanx. The aim of this study was to examine the reliability of new radiographic measurements that consider the elevation of the first metatarsal in relation to the proximal phalanx, rather than in relation to the second metatarsal as previously described, to assess for MPE. In addition, we aimed to determine whether the elevation of the first metatarsal was significantly different in patients with hallux rigidus than in a control population. Methods: A retrospective chart review was conducted from prospectively collected registry data at the investigators’ institution to identify patients with hallux rigidus ( n = 65). A size-matched control cohort of patients without evidence for first metatarsophalangeal (MTP) joint arthritis was identified ( n = 65). Patients with a previous history of foot surgery, rheumatoid arthritis, or hallux valgus were excluded. Five blinded raters of varying levels of training, including 2 research assistants, 1 senior orthopedic resident, 1 foot and ankle fellowship-trained orthopedic surgeon, and 1 attending musculoskeletal fellowship-trained radiologist, evaluated 7 radiographic measurements for their reliability in assessing for MPE in hallux rigidus and control groups. Four of the 7 were newly designed measurements that include the relationship of the first MTP joint. Inter- and intrarater reliability were calculated using intraclass correlation coefficients (ICCs) and categorized by Landis and Koch reliability thresholds. The measurements between the hallux rigidus and control populations were compared using an independent t test. Results: Six of the 7 radiographic measurements were found to have substantial to almost perfect interrater reliability (ICC, 0.800-0.953) between all levels of training, except for the proximal phalanx–first metatarsal angle, which showed moderate reliability (ICC, 0.527). Substantial to almost perfect intrarater reliability (ICC, 0.710-0.982) was demonstrated by the measurements performed by research assistants. All 7 of the measurements taken by the musculoskeletal fellowship-trained radiologist demonstrated significant differences in first metatarsal elevation between the hallux rigidus and control populations, with the hallux rigidus group showing increased elevation ( P < .001-.019). Conclusion: This study confirmed the reliability of 7 radiographic measurements used to assess for MPE, including 3 previously established and 4 newly described measurements. Observers across all levels of training were able to demonstrate reliable measurements. In addition, the measurements were used to show that patients with hallux rigidus were more likely to have MPE compared with patients without radiographic evidence for first MTP arthritis. These measurements could be used in future work to examine how the presence of MPE relates to the etiology and progression of hallux rigidus, and how it affects the results of operative treatment. Level of Evidence: Level III, retrospective comparative study.

Negative symptoms and depression persist in one third of patients with schizophrenia. Previous studies suggested that depression has more impact on self-perceived compared to observer-rated social functions. Reduced emotional experience, a subdomain of negative symptoms, predicts social functioning deficits, although its role in self-assessment is unclear. We examined depression and reduced emotional experience and self-reports and informant ratings of social functioning and social cognitive abilities in 135 patients with schizophrenia. Discrepancies between sources were used to index the accuracy and bias in self-assessment. Less severe depression was associated with self-reports of reduced impairments in social functioning and better social cognitive abilities. Reduced emotional experience was related to informant ratings and self-reports of social functioning. Neither reduced emotional experience nor depression was correlated with discrepancies between sources, despite the bias of patients with lower depression to report that they were higher functioning and more competent. These findings suggest that patients with schizophrenia make global judgments about functioning based on current mood states. There was minimal association between the depression severity and the accuracy of self-assessment, despite positive biases associated with lower depression severity. The determinants of accuracy and bias in self-assessment requires more detailed examination and subdivision of patients based on their depression.

Cell and tissue degeneration, and the development of degenerative diseases, are influenced by genetic and environmental factors that affect protein misfolding and proteotoxicity. To better understand the role of the environment in degeneration, we developed a genetic model for heat shock (HS)-stress-induced degeneration in Drosophila. This model exhibits a unique combination of features that enhance genetic analysis of degeneration and protection mechanisms involving environmental stress. These include cell-type-specific failure of proteostasis and degeneration in response to global stress, cell-nonautonomous interactions within a simple and accessible network of susceptible cell types, and precise temporal control over the induction of degeneration. In wild-type flies, HS stress causes selective loss of the flight ability and degeneration of three susceptible cell types comprising the flight motor: muscle, motor neurons and associated glia. Other motor behaviors persist and, accordingly, the corresponding cell types controlling leg motor function are resistant to degeneration. Flight motor degeneration was preceded by a failure of muscle proteostasis characterized by diffuse ubiquitinated protein aggregates. Moreover, muscle-specific overexpression of a small heat shock protein (HSP), HSP23, promoted proteostasis and protected muscle from HS stress. Notably, neurons and glia were protected as well, indicating that a small HSP can mediate cell-nonautonomous protection. Cell-autonomous protection of muscle was characterized by a distinct distribution of ubiquitinated proteins, including perinuclear localization and clearance of protein aggregates associated with the perinuclear microtubule network. This network was severely disrupted in wild-type preparations prior to degeneration, suggesting that it serves an important role in muscle proteostasis and protection. Finally, studies of resistant leg muscles revealed that they sustain proteostasis and the microtubule cytoskeleton after HS stress. These findings establish a model for genetic analysis of degeneration and protection mechanisms involving contributions of environmental factors, and advance our understanding of the protective functions and therapeutic potential of small HSPs.

Gulf War Illness (GWI) is a multisymptom disorder including widespread chronic pain, fatigue and gastrointestinal problems. The objective of this study was to examine the low glutamate diet as a treatment for GWI. Forty veterans with GWI were recruited from across the US. Outcomes included symptom score, myalgic score, tender point count, dolorimetry and the Chalder Fatigue Scale. Subjects were randomized to the low glutamate diet or a wait-listed control group, with symptom score being compared after one month. Subjects then went onto a double-blind, placebo-controlled crossover challenge with monosodium glutamate (MSG)/placebo to test for return of symptoms. Symptom score was compared between diet intervention and wait-listed controls with an independent t-test and effect size was calculated with Cohen’s d. Change scores were analyzed with Wilcoxon Signed Rank tests. Crossover challenge results were analyzed with General Linear Models and cluster analysis. The diet intervention group reported significantly less symptoms (p = 0.0009) than wait-listed controls, with a very large effect size, d = 1.16. Significant improvements in average dolorimetry (p = 0.0006), symptom score, tender point number, myalgic score and the Chalder Fatigue Scale (all p < 0.0001) were observed after the 1-month diet. Challenge with MSG/placebo resulted in significant variability in individual response. These results suggest that the low glutamate diet can effectively reduce overall symptoms, pain and fatigue in GWI, but differential results upon challenge suggest that other aspects of the diet, or underlying differences within the population, may be driving these changes. Future research is needed to identify potential nutrient effects, biomarkers, and underlying metabolic differences between responders and non-responders.

Background: It is critical for patients seeking foot and ankle care to have access to quality online resources, as the treatment of their conditions may involve the use of a variety of diagnostic and therapeutic modalities with which they are unfamiliar. This study was performed to enhance our understanding of if and why patients use Internet-based educational materials, to identify trends in utilization, and to delineate the patient-perceived attributes of quality resources. Methods: Questionnaires were distributed to 150 adult foot and ankle patients. The questionnaire consisted of demographic and Internet utilization questions. Statistical analysis was performed to determine the frequency of responses for each question and the relationship between demographics and Internet usage. Results: Younger patients were more likely to use the Internet ( P = .006). However, there were no other significant differences in demographic attributes between patients who did (76%) and did not (24%) utilize the Internet ( P

Diffusion magnetic resonance imaging (dMRI) allows for a non-invasive visualization and quantitative assessment of white matter architecture in the brain by characterizing restrictions on the random motion of water molecules. Ultra-high field MRI scanners, such as those operating at 7 Tesla (7T) or higher, can boost the signal-to-noise ratio (SNR) to improve dMRI compared with what is attainable at conventional field strengths such as 3T or 1.5T. However, wavelength effects at 7T cause reduced transmit magnetic field efficiency in the human brain, mainly in the posterior fossa, manifesting as signal dropouts in this region. Recently, we reported a simple approach of using a wireless radiofrequency (RF) surface array to improve transmit efficiency and signal sensitivity at 7T. In this study, we demonstrate the feasibility and effectiveness of the RF enhancer in improving in vivo dMRI at 7T. The electromagnetic simulation results demonstrated a 2.1-fold increase in transmit efficiency with the use of the RF enhancer. The experimental results similarly showed a 1.9-fold improvement in transmit efficiency and a 1.4-fold increase in normalized SNR. These improvements effectively mitigated signal dropouts in regions with inherently lower SNR, such as the cerebellum, resulting in a better depiction of principal fiber orientations and an enhanced visualization of extended tracts. [ABSTRACT FROM AUTHOR]

Background: Perivascular spaces (PVS) are fluid-filled cavities surrounding small cerebral blood vessels. There are limited reports of enlarged PVS across the grey matter in manifest Huntington's disease (HD). Little is known about how PVS morphometry in the white matter may contribute to HD. Enlarged PVS have the potential to both contribute to HD pathology and affect the distribution and success of intraparenchymal and intrathecally administered huntingtin-lowering therapies. Objective: To investigate PVS morphometry in the global white matter across the spectrum of HD. Relationships between PVS morphometry and disease burden and severity measures were examined. Methods: White matter PVS were segmented on 3T T2 W MRI brain scans of 33 healthy controls, 30 premanifest HD (pre-HD), and 32 early manifest HD (early-HD) participants from the Vancouver site of the TRACK-HD study. PVS count and total PVS volume were measured. Results: PVS total count slightly increased in pre-HD (p = 0.004), and early-HD groups (p = 0.005), compared to healthy controls. PVS volume, as a percentage of white matter volume, increased subtly in pre-HD compared to healthy controls (p = 0.044), but not in early-HD. No associations between PVS measures and HD disease burden or severity were found. Conclusions: This study reveals relatively preserved PVS morphometry across the global white matter of pre-HD and early-HD. Subtle morphometric abnormalities are implied but require confirmation in a larger cohort. However, in conjunction with previous publications, further investigation of PVS in HD and its potential impact on future treatments, with a focus on subcortical grey matter, is warranted. [ABSTRACT FROM AUTHOR]

Background: Alcohol use disorder (AUD) affects 283 million people worldwide and its prevalence is increasing. Despite the role of the cerebellum in executive control and its sensitivity to alcohol, few studies have assessed its involvement in AUD‐relevant functional networks. The goal of this study is to compare resting‐state functional connectivity (FC) patterns in abstinent adults with a history of AUD and controls (CTL). We hypothesized that group differences in cerebro‐cerebellar FC would be present, particularly within the frontoparietal/executive control network (FPN). Methods: Twenty‐eight participants completed a resting‐state functional magnetic resonance imaging (rsfMRI) study. CTL participants had no history of AUD, comorbid psychological conditions, or recent heavy drinking and/or drug use. AUD participants had a history of AUD, with sobriety for at least 30 days prior to data collection. Multivariate pattern analysis, an agnostic, whole‐brain approach, was used to identify regions with significant differences in FC between groups. Seed‐based analyses were then conducted to determine the directionality and extent of these FC differences. Associations between FC strength and executive function were assessed using correlations with Wisconsin Card Sorting Test (WCST) performance. Results: There were significant group differences in FC in nodes of the FPN, ventral attention network, and default mode network. Post hoc analyses predominantly identified FC differences within the cerebro‐cerebellar FPN, with AUD showing significantly less FC within the FPN. In AUD, FC strength between FPN clusters identified in the multivariate pattern analysis (MVPA) analysis (Left Crus II, Right Frontal Cortex) was positively associated with performance on the WCST. Conclusions: Our results show less engagement of the FPN in individuals with AUD than in CTL. FC strength within this network was positively associated with performance on the WCST. These findings suggest that long‐term heavy drinking alters cerebro‐cerebellar FC, particularly within networks that are involved in executive function. [ABSTRACT FROM AUTHOR]