Neural differentiation is moderated by age in scene- but not face-selective cortical regions

The aging brain is characterized by neural dedifferentiation, an apparent decrease in the functional selectivity of category-selective cortical regions. Age-related reductions in neural differentiation have been proposed to play a causal role in cognitive aging. Recent findings suggest, however, that age-related dedifferentiation is not equally evident for all stimulus categories and, additionally, that the relationship between neural differentiation and cognitive performance is not moderated by age. In light of these findings, in the present experiment, younger and older human adults (males and females) underwent fMRI as they studied words paired with images of scenes or faces before a subsequent memory task. Neural selectivity was measured in two scene-selective (parahippocampal place area (PPA) and retrosplenial cortex (RSC)] and two face-selective [fusiform face area (FFA) and occipital face area (OFA)] regions using both a univariate differentiation index and multivoxel pattern similarity analysis. Both methods provided highly convergent results, which revealed evidence of age-related reductions in neural dedifferentiation in scene-selective but not face-selective cortical regions. Additionally, neural differentiation in the PPA demonstrated a positive, age-invariant relationship with subsequent source memory performance (recall of the image category paired with each recognized test word). These findings extend prior findings suggesting that age-related neural dedifferentiation is not a ubiquitous phenomenon, and that the specificity of neural responses to scenes is predictive of subsequent memory performance independently of age

Age differences in retrieval-related reinstatement reflect age-related dedifferentiation at encoding

Age-related reductions in neural selectivity have been linked to cognitive decline. We examined whether age differences in the strength of retrieval-related cortical reinstatement could be explained by analogous differences in neural selectivity at encoding, and whether reinstatement was associated with memory performance in an age-dependent or an age-independent manner. Young and older adults underwent fMRI as they encoded words paired with images of faces or scenes. During a subsequent scanned memory test participants judged whether test words were studied or unstudied and, for words judged studied, also made a source memory judgment about the associated image category. Using multi-voxel pattern similarity analyses, we identified robust evidence for reduced scene reinstatement in older relative to younger adults. This decline was however largely explained by age differences in neural differentiation at encoding; moreover, a similar relationship between neural selectivity at encoding and retrieval was evident in young participants. The results suggest that, regardless of age, the selectivity with which events are neurally processed at the time of encoding can determine the strength of retrieval-related cortical reinstatement

Distinct neurophysiological correlates of the fMRI BOLD signal in the hippocampus and neocortex

Functional magnetic resonance imaging (fMRI) is among the foremost methods for mapping human brain function but provides only an indirect measure of underlying neural activity. Recent findings suggest that the neurophysiological correlates of the fMRI blood oxygenation level-dependent (BOLD) signal might be regionally specific. We examined the neurophysiological correlates of the fMRI BOLD signal in the hippocampus and neocortex, where differences in neural architecture might result in a different relationship between the respective signals. Fifteen human neurosurgical patients (10 female, 5 male) implanted with depth electrodes performed a verbal free recall task while electrophysiological activity was recorded simultaneously from hippocampal and neocortical sites. The same patients subsequently performed a similar version of the task during a later fMRI session. Subsequent memory effects (SMEs) were computed for both imaging modalities as patterns of encoding-related brain activity predictive of later free recall. Linear mixed-effects modeling revealed that the relationship between BOLD and gamma-band SMEs was moderated by the lobar location of the recording site. BOLD and high gamma (70–150 Hz) SMEs positively covaried across much of the neocortex. This relationship was reversed in the hippocampus, where a negative correlation between BOLD and high gamma SMEs was evident. We also observed a negative relationship between BOLD and low gamma (30–70 Hz) SMEs in the medial temporal lobe more broadly. These results suggest that the neurophysiological correlates of the BOLD signal in the hippocampus differ from those observed in the neocortex

2020-04-15 DAILY UNM GLOBAL HEALTH COVID-19 BRIEFING

Executive Summary: Daily NM recap. NM Hospital financial challenges. NM absentee voting. NM dairy farmers impact. 19-20 states open May 1? USA halts WHO funding. More NYC deaths. 250K tests AZ first responders. Global pandemic updates. Imported cases China. Masked South Korea elections. Danish children school return. PPE angiography. NYC cancels healthcare workers. GI shedding endoscopes. Blockade reduces transmission. Fever screening. Viral shedding post seroconversion. Radiology mitigations. Endoscopy units. Tracheostomy reduced transmission. Survivors plasma. Medical Imaging. Useful CTs. Electrophysiology procedures. Renin angiotensin blockers. Hemostasis. Dermatologic surgery. Pediatric gastroenterology. Autoimmune liver disease. Orthopedic surgical care. Updated treatment evidence. Asymptomatic detection. CVD pharmacology. Bleach disinfection. Arbidol beats lopinavir/ritonavir. IV immunoglobulin therapy. No HCQ clinical efficacy. Cepharantine inhibition pangolins. Machine learning antivirals. Eat bitter substances. 59 new trials. Combining RNA and antibody tests. No SARS-CoV-2 in patient ward air. Influenza impact prevention. Encephalitis. Low CD4+ and CD8+ severe. G6PD-deficient issues. Cytokine storm. Biosensor detection. Immunopathogenesis

2020-04-10 DAILY UNM GLOBAL HEALTH COVID-19 BRIEFING

Executive Summary: Extra NM HSD SNAP benefits. NM cases \u3e1000. Meds supply chain threatened. Mass graves in NY. Surgeon General screening app. Presidential briefing. Italian healthcare worker deaths. Taiwan tiered care model. Communicating risks to public. French public demand hydroxychloroquine. Vaccination pause dangers. Retesting needed after discharge. CDC report geography and incidence. UW clinical informatics response. UW preparedness guidelines. Wuhan outbreak control. CDC asymptomatic exposed worker guidelines. Mask innovation. Unemployment spikes. Workforce gaps. Workspace modifications reduce transmission. Guidelines and recommendations: ER physician, surgery, cardiopulmonary resuscitation, chest imaging, geriatrics, critically ill children, postpyloric tube placement, genitourinary malignancies, obstetrics, and home work health. Remdesivir clinically promising. Hydroxychloroquine safe but higher mortality with azithromycin. Lockdown health risks. Post-ICU syndrome. Tetracyline therapy potential. ACE2 review. Repurposing candidates. Patient self-triage tool. Video of aerosol spread and lingering. Modeling challenges. 34 new clinical trials registered today

2020-04-14 DAILY UNM GLOBAL HEALTH COVID-19 BRIEFING

Executive Summary: NMDOH county demographics online. NM emergency business loans. ABQ businesses violations. NM 5 new deaths 62 more cases. May 1 reopening too optimistic. MA contract tracing. Federal Ventilator Reserve. GM mass ventilator production. Ventilator-sharing device. $400M N-95 mask sterilization 60 sites. UNM PPE reprocessing online. Drug quality vulnerable. Managing urgent airway calls. Social distancing until 2022. SARS-Cov-2 blood supply. Contact tracing national blueprint. Mental health endangered. Successful surgical rapid response. Contact tracing medical ethics. Animal coronaviruses: human lessons. IDSA management guidelines. Ophthalmic practice. Pain management. Obstetrics management. Oncology practice. Forward triage. Scoring time-sensitive procedures. Outpatient structural heart disease. Thoracic surgery outcomes. Chest CT screening: epidemics. Sarcoma management. Endocrine diseases. Clinical pharmacists\u27 strategies. Non-invasive ventilation benefits. Essential laboratory testing. Psychiatric service. Hydroxychloroquine negative RCT. JAMA pharmacologic Tx review. Convalescent plasma. Promising antivirals. 55 clinical trials today. NYC hospitalization risk factors. Children milder disease. Blood morphology anomalies. No antimalarial consensus

2020-04-11/12 DAILY UNM GLOBAL HEALTH COVID-19 BRIEFING

Executive Summary: No NM church gatherings. NM a testing champ. Consolidation of elderly care. NM case update. 50-state disaster. Ventilator haggling. Economy reopening planning. PPE decontamination. Hospital ward contamination. Prolonged return to normal. FEMA projections. WHO tracking app. China SEIR model. Hubei epi. Mortality best measure. Covid-19 wave 2. Public should wear masks. Civil liberties. Safe grocery shopping. School closure impact. CDC caretaker guidelines. Psychiatric mobilization. Keep newborns with mom. C-section protocol. Italian obstetrics. Pediatric cardiac catherization. Chinese anesthesiology consensus. Cancer guidelines. Neuro-oncologic Tx. Radiology algorithm. Lung ultrasonography. ARF care. VTE common and predictable. Liver transplantation. Auto-immune treatments. Extracorporeal kidney involvement. Nutrition support. GI endoscopy. No stay-at-home for stroke. Intensive care collaboration. Supine swab collection. Lab tests for severity. Testing assay performance. False negative RT-PCR tests. IgM and IgG serum tests. FDA convalescent plasma. Blood purification device approval. Erythropoietin treatment. Tissue plasminogen activator. ECMO. Lopinavir/ritonavir study results. Immunotherapy review. Vaccine development. Hydroxychloroquine review. Candidates from in silico/virtual screening. Traditional Indian therapies. US trials update. Pathways and risk factors for death. ACE2 polymorphism. Severity in children. Lung tissue replication. Phylogenetic tracing. Text mining dataset. Risk by blood type

NMR Solution Structure of the Focal Adhesion Targeting Domain of Focal Adhesion Kinase in Complex with a Paxillin LD Peptide: EVIDENCE FOR A TWO-SITE BINDING MODEL

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that is regulated by integrins. Upon activation, FAK generates signals that modulate crucial cell functions, including cell proliferation, migration, and survival. The C-terminal focal adhesion targeting (FAT) sequence mediates localization of FAK to discrete regions in the cell called focal adhesions. Several binding partners for the FAT domain of FAK have been identified, including paxillin. We have determined the solution structure of the avian FAT domain in complex with a peptide mimicking the LD2 motif of paxillin by NMR spectroscopy. The FAT domain retains a similar fold to that found in the unliganded form when complexed to the paxillin-derived LD2 peptide, an antiparallel four-helix bundle. However, noticeable conformational changes were observed upon the LD2 peptide binding, especially the position of helix 4. Multiple lines of evidence, including the results obtained from isothermal titration calorimetry, intermolecular nuclear Overhauser effects, mutagenesis, and protection from paramagnetic line broadening, support the existence of two distinct paxillin-binding sites on the opposite faces of the FAT domain. The structure of the FAT domain-LD2 complex was modeled using the program HADDOCK based on our solution structure of the LD2-bound FAT domain and mutagenesis data. Our model of the FAT domain-LD2 complex provides insight into the molecular basis of FAK-paxillin binding interactions, which will aid in understanding the role of paxillin in FAK targeting and signaling

Signature for Pain Recovery IN Teens (SPRINT): protocol for a multisite prospective signature study in chronic musculoskeletal pain

INTRODUCTION: Current treatments for chronic musculoskeletal (MSK) pain are suboptimal. Discovery of robust prognostic markers separating patients who recover from patients with persistent pain and disability is critical for developing patient-specific treatment strategies and conceiving novel approaches that benefit all patients. Given that chronic pain is a biopsychosocial process, this study aims to discover and validate a robust prognostic signature that measures across multiple dimensions in the same adolescent patient cohort with a computational analysis pipeline. This will facilitate risk stratification in adolescent patients with chronic MSK pain and more resourceful allocation of patients to costly and potentially burdensome multidisciplinary pain treatment approaches. METHODS AND ANALYSIS: Here we describe a multi-institutional effort to collect, curate and analyse a high dimensional data set including epidemiological, psychometric, quantitative sensory, brain imaging and biological information collected over the course of 12 months. The aim of this effort is to derive a multivariate model with strong prognostic power regarding the clinical course of adolescent MSK pain and function. ETHICS AND DISSEMINATION: The study complies with the National Institutes of Health policy on the use of a single internal review board (sIRB) for multisite research, with Cincinnati Children's Hospital Medical Center Review Board as the reviewing IRB. Stanford's IRB is a relying IRB within the sIRB. As foreign institutions, the University of Toronto and The Hospital for Sick Children (SickKids) are overseen by their respective ethics boards. All participants provide signed informed consent. We are committed to open-access publication, so that patients, clinicians and scientists have access to the study data and the signature(s) derived. After findings are published, we will upload a limited data set for sharing with other investigators on applicable repositories. TRIAL REGISTRATION NUMBER: NCT04285112