Bihemispheric network dynamics coordinating vocal feedback control

Modulation of vocal pitch is a key speech feature that conveys important linguistic and affective information. Auditory feedback is used to monitor and maintain pitch. We examined induced neural high gamma power (HGP) (65–150 Hz) using magnetoencephalography during pitch feedback control. Participants phonated into a microphone while hearing their auditory feedback through headphones. During each phonation, a single real‐time 400 ms pitch shift was applied to the auditory feedback. Participants compensated by rapidly changing their pitch to oppose the pitch shifts. This behavioral change required coordination of the neural speech motor control network, including integration of auditory and somatosensory feedback to initiate change in motor plans. We found increases in HGP across both hemispheres within 200 ms of pitch shifts, covering left sensory and right premotor, parietal, temporal, and frontal regions, involved in sensory detection and processing of the pitch shift. Later responses to pitch shifts (200–300 ms) were right dominant, in parietal, frontal, and temporal regions. Timing of activity in these regions indicates their role in coordinating motor change and detecting and processing of the sensory consequences of this change. Subtracting out cortical responses during passive listening to recordings of the phonations isolated HGP increases specific to speech production, highlighting right parietal and premotor cortex, and left posterior temporal cortex involvement in the motor response. Correlation of HGP with behavioral compensation demonstrated right frontal region involvement in modulating participant's compensatory response. This study highlights the bihemispheric sensorimotor cortical network involvement in auditory feedback‐based control of vocal pitch. Hum Brain Mapp 37:1474‐1485, 2016. © 2016 Wiley Periodicals, Inc.     

Novel mutation in MAPT exon 13 (p.N410H) causes corticobasal degeneration

In order to determine the frequency of microtubule-associated protein tau gene (MAPT) mutations and rare variants in CBD, we performed a systematic sequence analysis of MAPT coding and 3′ untranslated region (3′UTR) in a large cohort of autopsy-confirmed CBD patients (N = 109). This identified a novel MAPT mutation in exon 13, p.N410H, in a case that is neuropathologically indistinguishable from sporadic CBD. On immunoblot, the p.N410H mutation carrier had the same insoluble tau profile as seen in CBD. Additionally, tau expression analysis in brain tissue found a significant increase in the 4R/3R tau mRNA ratio (P = 0.04), indicating that p.N410H disrupts tau isoform homeostasis. Biochemically, recombinant tau protein with p.N410H showed a marked increase in tau filament formation compared to wild-type tau (P < 0.001), had a 19.2 % decrease in rate of microtubule assembly (P < 0.05), and a 10.3 % reduction in the extent of total microtubule polymerization (P < 0.01). Sequence analysis of the complete MAPT 3′UTR in autopsy-confirmed CBD cases further identified two rare variants with nominally significant association with CBD. An ATC nucleotide insertion (“MAPTv8”) was found in 4.6 % of CBD patients compared to 1.2 % of controls (P = 0.031, OR = 3.71), and rs186977284 in 4.6 % CBD patients, but only 0.9 % of controls (P = 0.04, OR = 3.58). Rs186977284 was also present in 2.7 % of a large cohort of autopsy-confirmed PSP patients (N = 566) and only 0.9 % of an additional control series (P = 0.034, OR = 3.08), extending the association to PSP. Our findings show that mutations in MAPT can cause CBD and MAPT non-coding variants may increase the risk of complex 4R tauopathies.     

Symtoms and Social Adjustment of Schizophrenic Patients as Evaluated by Their Family Members: A Cross-Cultural Psychiatric Study between Offshore Islands and an Urban City

Abstract: We conducted a comparative study of symptoms and social adjustment of schizophrenic patients on offshore islands and one urban region in Japan. In the evaluation of symptoms and social behavior by family members, no differences were observed between the two regions. Looking at social adjustment in the two regions, no differences were observed by family members either in the performance level or in the expectation level of socially expected activities. However, on the offshore islands, the expectation level of socially expected activities by family members was significantly higher than the level of self-accomplishment set by schizophrenic patients themselves. As for leisure activities, both family members and patients on the islands evaluated the level of performance to be significantly higher than in the urban region, and the level of satisfaction of the patients themselves was also higher on the islands. Considering both these findings and Japanese traditional views of work and leisure, it is believed that on the islands patients are required to engage in more productive activities and less leisure activities than in the urban region. Further it seems that patients on the islands compared to patients in the urban region may have greater difficulty in social adjustment.     

Patterns of cerebral injury and clinical presentation in the vascular disruptive syndrome of monozygotic twins

The prenatal histories, clinical courses, and neuroradiographic studies of 8 infants who had survived the in utero demise of a homozygous co-twin were reviewed. Three distinct modes of clinical presentation were found: (1) severe neonatal encephalopathy with seizures; (2) a more benign neonatal course with onset of seizures and profound developmental disabilities within the first 6 months of age; (3) late infantile presentation with seizures. Only the third group had milder outcomes. Neuroradiographic studies demonstrated two pathologic patterns: varying degrees of periventricular white matter infarction with migrational abnormalities observed with earlier demise of the co-twin, and multicystic encephalomalacia observed when the demise occurred at or near term. Pathophysiology is uncertain and most likely multifactorial. Exsanguination injury to the survivor can occur acutely following co-twin demise, so urgent delivery may be appropriate at or near term.     

The intrinsic flexibility of IgE and its role in binding FcepsilonRI.

The interaction between IgE and its high affinity cellular receptor (FcepsilonRI) is an essential step in the development of allergic responses. Studies have identified the third constant domain of IgE (Cepsilon3) as the receptor binding region. The Cepsilon3 domain has unusual structural features; it was found to be a 'molten globule' structure in an isolated form, only assuming a well structured form upon binding to FcepsilonRI. The conformational flexibility intrinsic to the receptor binding portion of the molecule may be useful to IgE in allowing the large allosteric changes postulated to be required for FcepsilonRI engagement. If allosteric inhibitors can be developed then the dynamic properties of the Cepsilon3 domain may provide opportunities for therapeutic intervention in allergic disorders.     

Identification of the memory component that decays with age in Drosophila]

No one can escape from memory decay with advancing age. Understanding molecular mechanisms underlying age-related memory impairment (AMI) is important not only from the scientific viewpoint but also for elucidating novel targets that may eventually lead to developing therapeutics for combating memory loss. AMI had been generally considered to be an overall or nonspecific decay of memory processes that results from dysfunction of neural networks. However, behavioral genetic tests of this hypothesis have not been carried out. Using Drosophila, we have demonstrated the first extensive behavioral-genetic characterization of AMI. We discovered that AMI results from the specific decay of only one memory component, amnesiac-dependent middle-term memory, and not other components. In support of this finding, we show that memory in aged flies is identical to that of amnesiac mutants, and while other memory mutants show a further decrease in memory upon aging, amnesiac flies do not. These results provide the first identification of a specific gene pathway underlying AMI.     

Guidelines for the prevention of intravascular catheter-related infections. Centers for Disease Control and Prevention.

These guidelines have been developed for practitioners who insert catheters and for persons responsible for surveillance and control of infections in hospital, outpatient, and home health-care settings. This report was prepared by a working group comprising members from professional organizations representing the disciplines of critical care medicine, infectious diseases, health-care infection control, surgery anesthesiology interventional radiology pulmonary medicine, pediatric medicine, and nursing. The working group was led by the Society of Critical Care Medicine (SCCM), in collaboration with the Infectious Disease Society of America (IDSA), Society for Healthcare Epidemiology ofAmerica (SHEA), Surgical Infection Society (SIS), American College of Chest Physicians (ACCP), American Thoracic Society (ATS), American Society of Critical Care Anesthesiologists (ASCCA), Association for Professionals in Infection Control and Epidemiology (APIC), Infusion Nurses Society (INS), Oncology Nursing Society (ONS), Society of Cardiovascular and Interventional Radiology (SCVIR), American Academy of Pediatrics (AAP), and the Healthcare Infection Control Practices Advisory Committee (HICPAC) of the Centers for Disease Control and Prevention (CDC) and is intended to replace the Guideline for Prevention of Intravascular Device-Related Infections published in 1996 These guidelines are intended to provide evidence-based recommendations for preventing catheter-related infections. Major areas of emphasis include 1) educating and training health-care providers who insert and maintain catheters; 2) using maximal sterile barrier precautions during central venous catheter insertion; 3) using a 2% chlorhexidine preparation for skin antisepsis; 4) avoiding routine replacement of central venous catheters as a strategy to prevent infection; and 5) using antiseptic/antibiotic impregnated short-term central venous catheters if the rate of infection is high despite adherence to other strategies (i.e., education and training, maximal sterile barrier precautions, and 2% chlorhexidine for skin antisepsis). These guidelines also identify performance indicators that can be used locally by health-care institutions or organizations to monitor their success in implementing these evidence-based recommendations.