Neurosystems: brain rhythms and cognitive processing

Neuronal rhythms are ubiquitous features of brain dynamics, and are highly correlated with cognitive processing. However, the relationship between the physiological mechanisms producing these rhythms and the functions associated with the rhythms remains mysterious. This article investigates the contributions of rhythms to basic cognitive computations (such as filtering signals by coherence and/or frequency) and to major cognitive functions (such as attention and multi-modal coordination). We offer support to the premise that the physiology underlying brain rhythms plays an essential role in how these rhythms facilitate some cognitive operations.098352 - Wellcome Trust; 5R01NS067199 - NINDS NIH HH

Fibulin-4 is essential for maintaining arterial wall integrity in conduit but not muscular arteries

Homozygous or compound heterozygous mutations in fibulin-4 (FBLN4) lead to autosomal recessive cutis laxa type 1B (ARCL1B), a multisystem disorder characterized by significant cardiovascular abnormalities, including abnormal elastin assembly, arterial tortuosity, and aortic aneurysms. We sought to determine the consequences of a human disease-causing mutation in FBLN4 (E57K) on the cardiovascular system and vascular elastic fibers in a mouse model of ARCL1B. Fbln4E57K/E57K mice were hypertensive and developed arterial elongation, tortuosity, and ascending aortic aneurysms. Smooth muscle cell organization within the arterial wall of large conducting vessels was abnormal, and elastic fibers were fragmented and had a moth-eaten appearance. In contrast, vessel wall structure and elastic fiber integrity were normal in resistance/muscular arteries (renal, mesenteric, and saphenous). Elastin cross-linking and total elastin content were unchanged in large or small arteries, whereas elastic fiber architecture was abnormal in large vessels. While the E57K mutation did not affect Fbln4 mRNA levels, FBLN4 protein was lower in the ascending aorta of mutant animals compared to wild-type arteries but equivalent in mesenteric arteries. We found a differential role of FBLN4 in elastic fiber assembly, where it functions mainly in large conduit arteries. These results suggest that elastin assembly has different requirements depending on vessel type. Normal levels of elastin cross-links in mutant tissue call into question FBLN4\u27s suggested role in mediating lysyl oxidase-elastin interactions. Future studies investigating tissuespecific elastic fiber assembly may lead to novel therapeutic interventions for ARCL1B and other disorders of elastic fiber assembly. 2017 © The Authors, some rights reserved

The clinical spectrum of SMA-PME and in vitro normalization of its cellular ceramide profile

OBJECTIVE: The objectives of this study were to define the clinical and biochemical spectrum of spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) and to determine if aberrant cellular ceramide accumulation could be normalized by enzyme replacement. METHODS: Clinical features of 6 patients with SMA-PME were assessed by retrospective chart review, and a literature review of 24 previously published cases was performed. Leukocyte enzyme activity of acid ceramidase was assessed with a fluorescence-based assay. Skin fibroblast ceramide content and was assessed by high performance liquid chromatography, electrospray ionization tandem mass spectroscopy. Enzyme replacement was assessed using recombinant human acid ceramidase (rhAC) in vitro. RESULTS: The six new patients showed the hallmark features of SMA-PME, with variable initial symptom and age of onset. Five of six patients carried at least one of the recurrent SMA-PME variants observed in two specific codons of ASAH1. A review of 30 total cases revealed that patients who were homozygous for the most common c.125C \u3e T variant presented in the first decade of life with limb-girdle weakness as the initial symptom. Sensorineural hearing loss was associated with the c.456A \u3e C variant. Leukocyte acid ceramidase activity varied from 4.1%-13.1% of controls. Ceramide species in fibroblasts were detected and total cellular ceramide content was elevated by 2 to 9-fold compared to controls. Treatment with rhAC normalized ceramide profiles in cultured fibroblasts to control levels within 48 h. INTERPRETATION: This study details the genotype-phenotype correlations observed in SMA-PME and shows the impact of rhAC to correct the abnormal cellular ceramide profile in cells

Teaching Children with Autism to Understand Metaphors

The purpose of this study was to evaluate the effects of an instructional procedure on the acquisition and generalization of metaphorical understanding for children with autism spectrum disorder. Three students (two boys, one girl, 5-8 years old) participated but only two completed the study. A multiple-probe design across two behaviors and three participants was used. The metaphors were categorized by topography: metaphors involving physical features and metaphors involving abstract properties. The instruction consisted of intraverbal training using echoic prompts, picture prompts, and textual prompts. The results indicated that the instruction was effective in establishing metaphorical understanding of target metaphors. Generalized understanding to untaught metaphors occurred for the two students who completed the study, and all metaphors were maintained at a relatively high level for two months following the instruction

Reading Performance is Predicted by More Than Phonological Processing

We compared three phonological processing components (phonological awareness, rapid automatized naming and phonological memory), verbal working memory, and attention control in terms of how well they predict the various aspects of reading: word recognition, pseudoword decoding, fluency and comprehension, in a mixed sample of 182 children ages 8–12 years. Participants displayed a wide range of reading ability and attention control. Multiple regression was used to determine how well the phonological processing components, verbal working memory, and attention control predict reading performance. All equations were highly significant. Phonological memory predicted word identification and decoding. In addition, phonological awareness and rapid automatized naming predicted every aspect of reading assessed, supporting the notion that phonological processing is a core contributor to reading ability. Nonetheless, phonological processing was not the only predictor of reading performance. Verbal working memory predicted fluency, decoding and comprehension, and attention control predicted fluency. Based upon our results, when using Baddeley’s model of working memory it appears that the phonological loop contributes to basic reading ability, whereas the central executive contributes to fluency and comprehension, along with decoding. Attention control was of interest as some children with ADHD have poor reading ability even if it is not sufficiently impaired to warrant diagnosis. Our finding that attention control predicts reading fluency is consistent with prior research which showed sustained attention plays a role in fluency. Taken together, our results suggest that reading is a highly complex skill that entails more than phonological processing to perform well

Effects of intergenerational Montessori-based activities programming on engagement of nursing home residents with dementia

Fourteen nursing home residents on a dementia special care unit at a skilled nursing facility took part in one-to-one intergenerational programming (IGP) with 15 preschool children from the facility’s on-site child care center. Montessori-based activities served as the interface for interactions between dyads. The amount of time residents demonstrated positive and negative forms of engagement during IGP and standard activities programming was assessed through direct observation using a tool developed for this purpose – the Myers Research Institute Engagement Scale (MRI-ES). These residents with dementia displayed the ability to successfully take part in IGP. Most successfully presented “lessons” to the children in their dyads, similar to the way that Montessori teachers present lessons to children, while persons with more severe cognitive impairment took part in IGP through other methods such as parallel play. Taking part in IGP was consistently related with higher levels of positive engagement and lower levels of negative forms of engagement in these residents with dementia than levels seen in standard activities programming on the unit. Implications of using this form of IGP, and directions for future research, are discussed

Androgen action via testicular arteriole smooth muscle cells is important for leydig cell function, vasomotion and testicular fluid dynamics

Regulation of blood flow through the testicular microvasculature by vasomotion is thought to be important for normal testis function as it regulates interstitial fluid (IF) dynamics which is an important intra-testicular transport medium. Androgens control vasomotion, but how they exert these effects remains unclear. One possibility is by signalling via androgen receptors (AR) expressed in testicular arteriole smooth muscle cells. To investigate this and determine the overall importance of this mechanism in testis function, we generated a blood vessel smooth muscle cell-specific AR knockout mouse (SMARKO). Gross reproductive development was normal in SMARKO mice but testis weight was reduced in adulthood compared to control littermates; this reduction was not due to any changes in germ cell volume or to deficits in testosterone, LH or FSH concentrations and did not cause infertility. However, seminiferous tubule lumen volume was reduced in adult SMARKO males while interstitial volume was increased, perhaps indicating altered fluid dynamics; this was associated with compensated Leydig cell failure. Vasomotion was impaired in adult SMARKO males, though overall testis blood flow was normal and there was an increase in the overall blood vessel volume per testis in adult SMARKOs. In conclusion, these results indicate that ablating arteriole smooth muscle AR does not grossly alter spermatogenesis or affect male fertility but does subtly impair Leydig cell function and testicular fluid exchange, possibly by locally regulating microvascular blood flow within the testis

Advance Care Planning in Patients Undergoing Hematopoietic Cell Transplantation

AbstractFew data are available on the prevalence of advance care planning (ACP) in patients undergoing hematopoietic cell transplantation (HCT). We surveyed adult patients pre-HCT to ascertain completion of various elements of ACP. We also reviewed medical records for documentation of discussions regarding ACP and for the presence of written advance directives. Evaluable surveys were returned by 155 of 335 patients (46%) who underwent HCT during the study period; we obtained permission for medical record review from 137 of these 155 survey respondents (88%). We found that 69% of the respondents reported having designated a health care proxy, 44% had completed a living will, 61% had prepared an estate will, and 63% had discussed their wishes regarding life support with family and friends. In contrast, only 16% had discussed their wishes regarding life support with their clinicians. Documentation of discussions between clinicians and patients regarding most elements of ACP was rare. Written advance directives were present in the charts of 54 patients (39%). ACP was more common in older, college-educated, and allogeneic transplant patients. Even though ACP was more prevalent among this sample than in the general population, its use still could be enhanced, given the high risks of decisional incapacity and death that HCT patients face

Characteristics of Effective Metropolitan Areawide Public Transit: A Comparison of European, Canadian, and Australian Case Studies

This research project investigates the replicable characteristics, policies, and practices of successful metropolitan areawide public transportation networks that contribute to high usage and make transit an effective competitor to the private motor vehicle. The research method involves the qualitative and quantitative analysis of ten international (non-U.S.) case studies. The principal methods employed were web-based research and data collection, as well as telephone interviews with transit agency staff or regional planners as needed. The case studies were limited to developed western countries with similar metropolitan conditions to those in the United States. This research focuses on key characteristics of highly effective regional transit systems from the perspective of the metropolitan area, not the individual transit operators. These characteristics fall within three broad categories: the setting of the metropolitan area; the customer-apparent transit service features; and the behind-the-scenes or institutional characteristics. Key findings are: (1) all ten case studies have a metropolitan areawide regional transit coordinator (RTC); (2) RTCs yield benefits in terms of ridership and operating efficiencies that are discernable from the effects of high transit funding and subsidies; (3) all case studies had some degree of fare integration, and most had complete regionwide fare integration; and (4) transit service was frequent, abundant, and affordable in all cases. The features of excellent regionwide transit systems that have been identified in this research can be applied to U.S. metropolitan areas with multiple players, yielding effective, efficient, and high mode share public transit at the regional level. The research can help U.S. policy makers and planners begin to improve the appropriate aspects of their own regional transit systems, including by improving coordination and organizational structures