Neuroeducation – A Critical Overview of An Emerging Field

In the present article, we provide a critical overview of the emerging field of ‘neuroeducation’ also frequently referred to as ‘mind, brain and education’ or ‘educational neuroscience’. We describe the growing energy behind linking education and neuroscience in an effort to improve learning and instruction. We explore reasons behind such drives for interdisciplinary research. Reviewing some of the key advances in neuroscientific studies that have come to bear on neuroeducation, we discuss recent evidence on the brain circuits underlying reading, mathematical abilities as well as the potential to use neuroscience to design training programs of neurocognitive functions, such as working memory, that are expected to have effects on overall brain function. Throughout this review we describe how such research can enrich our understanding of the acquisition of academic skills. Furthermore, we discuss the potential for modern brain imaging methods to serve as diagnostic tools as well as measures of the effects of educational interventions. Throughout this discussion, we draw attention to limitations of the available evidence and propose future avenues for research. We also discuss the challenges that face this growing discipline. Specifically, we draw attention to unrealistic expectations for the immediate impact of neuroscience on education, methodological difficulties, and lack of interdisciplinary training, which results in poor communication between educators and neuroscientists. We point out that there should be bi-directional and reciprocal interactions between both disciplines of neuroscience and education, in which research originating from each of these traditions is considered to be compelling in its own right. While there are many obstacles that lie in the way of a productive field of neuroeducation, we contend that there is much reason to be optimistic and that the groundwork has been laid to advance this field in earnest.     

Impaired recognition of musical emotions and facial expressions following anteromedial temporal lobe excision

We have shown that an anteromedial temporal lobe resection can impair the recognition of scary music in a prior study (Gosselin et al., 2005). In other studies ( [Adolphs et?al., 2001] and [Anderson et?al., 2000] ), similar results have been obtained with fearful facial expressions. These findings suggest that scary music and fearful faces may be processed by common cerebral structures. To assess this possibility, we tested patients with unilateral anteromedial temporal excision and normal controls in two emotional tasks. In the task of identifying musical emotion, stimuli evoked either fear, peacefulness, happiness or sadness. Participants were asked to rate to what extent each stimulus expressed these four emotions on 10-point scales. The task of facial emotion included morphed stimuli whose expression varied from faint to more pronounced and evoked fear, happiness, sadness, surprise, anger or disgust. Participants were requested to select the appropriate label. Most patients were found to be impaired in the recognition of both scary music and fearful faces. Furthermore, the results in both tasks were correlated, suggesting a multimodal representation of fear within the amygdala. However, inspection of individual results showed that recognition of fearful faces can be preserved whereas recognition of scary music can be impaired. Such a dissociation found in two cases suggests that fear recognition in faces and in music does not necessarily involve exactly the same cerebral networks and this hypothesis is discussed in light of the current literature.     

Semaphorin 4C and 4G are ligands of Plexin-B2 required in cerebellar development

Semaphorins and Plexins are cognate ligand-receptor families that regulate important steps during nervous system development. The Plexin-B2 receptor is critically involved in neural tube closure and cerebellar granule cell development, however, its specific ligands have only been suggested by in vitro studies. Here, we show by in vivo and in vitro analyses that the two Semaphorin-4 family members Sema4C and Sema4G are likely to be in vivo ligands of Plexin-B2. The Sema4C and Sema4G genes are expressed in the developing cerebellar cortex, and Sema4C and Sema4G proteins specifically bind to Plexin-B2 expressing cerebellar granule cells. To further elucidate their in vivo function, we have generated and analyzed Sema4C and Sema4G knockout mouse mutants. Like Plexin-B2-/- mutants, Sema4C-/- mutants reveal exencephaly and subsequent neonatal lethality with partial penetrance. Sema4C-/- mutants that bypass exencephaly are viable and fertile, but display distinctive defects of the cerebellar granule cell layer, including gaps in rostral lobules, fusions of caudal lobules, and ectopic granule cells in the molecular layer. In addition to neuronal defects, we observed in Sema4C-/- mutants also ventral skin pigmentation defects that are similar to those found in Plexin-B2-/- mutants. The Sema4G gene deletion causes no overt phenotype by itself, but combined deletion of Sema4C and Sema4G revealed an enhanced cerebellar phenotype. However, Sema4C/Sema4G double mutants showed overall less severe cerebellar phenotypes than Plexin-B2-/- mutants, indicating that further ligands of Plexin-B2 exist. In explant cultures of the developing cerebellar cortex, Sema4C promoted migration of cerebellar granule cell precursors in a Plexin-B2-dependent manner, supporting the model that a reduced migration rate of granule cell precursors is the basis for the cerebellar defects of Sema4C-/- and Sema4C/Sema4G mutants.     

Ghrelin/obestatin ratio in two populations with low bodyweight: constitutional thinness and anorexia nervosa

Constitutional thinness (CT) and anorexia nervosa (AN) are two categories of severely underweight subjects. Some appetite-regulating hormones display opposite levels in AN and CT. While levels of ghrelin, an orexigenic hormone, fit with the normal food intake in CT, the lack of efficacy of increased ghrelin levels in AN is not clear. Obestatin is a recently described peptide derived from the preproghrelin gene, reported to inhibit appetite in contrast to ghrelin. The aim of this study was to determine whether the circadian profile of obestatin, total and acylated ghrelin levels is different in CT subjects when compared with AN patients. Six-points circadian profiles of plasma obestatin, acylated ghrelin, total ghrelin and other hormonal and nutritional parameters were evaluated in four groups of young women: 10 CT, 15 restricting-type AN, 7 restored from AN and 9 control subjects. Obestatin circadian levels were significantly higher in AN (p<0.0001) while no difference was found between CT and control subjects. Acylated and total ghrelin were found increased in AN. Acylated ghrelin/obestatin and total ghrelin/obestatin were found decreased in AN compared to CT or C subjects (p<0.05). The percentage of acylated ghrelin was found decreased in CT group (p<0.05). The decreased ghrelin/obestatin ratio found in AN might participate in the restraint in nutriment intake of these patients. In contrast, in CT a lower percentage of acylated over total ghrelin might be considered in the aetiology of this condition.     

A two-stage,single-arm,phase II study of EGCG-enriched green tea drink as a maintenance therapy in women with advanced stage ovarian cancer

Objectives

A two-stage, single-arm, phase II study was conducted to assess the effectiveness and safety of an epigallocatechin gallate (EGCG)-enriched tea drink, the double-brewed green tea (DBGT), as a maintenance treatment in women with advanced stage serous or endometrioid ovarian cancer (clinicaltrials.gov, NCT00721890).

Methods

Eligible women had FIGO stage III-IV serous or endometrioid ovarian cancer. They had to undergo complete response after debulking surgery followed by 6 to 8 cycles of platinum/taxane chemotherapy at the Centre Hospitalier Universitaire de Québec. They all had to drink the DBGT, 500 mL daily until recurrence or during a follow-up of 18 months. The primary endpoint was the absence of recurrence at 18 months. Statistical analyses were done according to the principle of intention to treat. Using a two-stage design, the first stage consisted of 16 enrolled patients. At the end of the follow-up, if 7 or fewer patients were free of recurrence, the trial stopped. Otherwise, accrual would continue to a total of 46 patients.

Results

During the first stage of the study, only 5 of the 16 women remained free of recurrence 18 months after complete response. Accordingly, the clinical trial was terminated. Women's adherence to DBGT was high (median daily intake during intervention, 98.1%, interquartile range: 89.7–100%), but 6 women discontinued the intervention before the end of their follow-up. No severe toxicity was reported.

Conclusions

DBGT supplementation does not appear to be a promising maintenance intervention in women with advanced stage ovarian cancer after standard treatment.     

Does an intracanal composite anchorage replace posts?

Objectives

This study aims to assess the effectiveness of an intracanal composite anchorage to replace conventionally cemented titanium or bonded glass fibre posts.

Materials and methods

Post space preparation was performed up to depths of 6 mm (groups 1 and 2) and 3 mm (group 3) in root filled mandibular premolars. In group 1, titanium posts were cemented with zinc phosphate cement. Glass fibre posts were adhesively cemented in group 2 using a dual-cure composite resin. In group 3, intracanal anchorage was solely performed with a dual-cure composite. All teeth were restored with standardised direct composite crowns without a ferrule. After thermo-mechanical loading, static load was applied until failure. Fracture patterns were assessed, and a microscopic analysis was performed to analyse the occurrence of additional cracks.

Results

Group 2 revealed a significantly higher median fracture value (408 N) than groups 1 and 3, while no difference was detected between group 1 (290 N) and group 3 (234 N) (p?=?.1417). In group 3, the more favourable fracture patterns were observed. However, the majority of teeth within this fracture category revealed additional minor cracks of the root.

Conclusions

Within the limitations of this study, adhesive intracanal anchorage to a depth of 3 mm with resin composite only has the same fracture resistance as titanium posts conventionally cemented to a depth of 6 mm. Even teeth with repairable main fractures exhibited additional dentinal cracks on the root.

Clinical relevance

Additional dentinal root cracks in the teeth with repairable main fractures may considerably impair their longevity.     

Efficacy of various side-to-side toothbrushes for noncontact biofilm removal

Objectives

The aim of this study was to evaluate the efficacy of four different powered toothbrushes with side-to-side action for noncontact biofilm removal in vitro.

Materials and methods

A three-species biofilm was formed in vitro on protein-coated titanium disks using a flow chamber combined with a static biofilm growth model. Subsequently, the biofilm-coated substrates were exposed to four different side-to-side toothbrushes (A, B, C, and D) with various brushing times (2, 4, and 6 s) and brushing (bristle-to-disk) distances (0, 2, and 4 mm). The biofilm volumes were measured using volumetric analyses with confocal laser scanning microscope images and Imaris version 7.5.2 software.

Results

The median percentages of biofilm reduction by the analyzed toothbrushes ranged from 9 % to 80 %. The abilities of the tested toothbrushes to remove the in vitro biofilm differed significantly (p?<?0.05). Two of the tested toothbrushes (C and D) were capable of significant biofilm reduction by noncontact brushing.

Conclusions

It was possible to reduce a three-species in vitro biofilm by noncontact brushing with two out of four side-to-side toothbrushes.

Clinical relevance

Toothbrushes C and D show in vitro a high efficacy in biofilm removal without bristle contact.     

Oxidative tissue injury in multiple sclerosis is only partly reflected in experimental disease models

Recent data suggest that oxidative injury may play an important role in demyelination and neurodegeneration in multiple sclerosis (MS). We compared the extent of oxidative injury in MS lesions with that in experimental models driven by different inflammatory mechanisms. It was only in a model of coronavirus-induced demyelinating encephalomyelitis that we detected an accumulation of oxidised phospholipids, which was comparable in extent to that in MS. In both, MS and coronavirus-induced encephalomyelitis, this was associated with massive microglial and macrophage activation, accompanied by the expression of the NADPH oxidase subunit p22phox but only sparse expression of inducible nitric oxide synthase (iNOS). Acute and chronic CD4⁺ T cell-mediated experimental autoimmune encephalomyelitis lesions showed transient expression of p22phox and iNOS associated with inflammation. Macrophages in chronic lesions of antibody-mediated demyelinating encephalomyelitis showed lysosomal activity but very little p22phox or iNOS expressions. Active inflammatory demyelinating lesions induced by CD8⁺ T cells or by innate immunity showed macrophage and microglial activation together with the expression of p22phox, but low or absent iNOS reactivity. We corroborated the differences between acute CD4⁺ T cell-mediated experimental autoimmune encephalomyelitis and acute MS lesions via gene expression studies. Furthermore, age-dependent iron accumulation and lesion-associated iron liberation, as occurring in the human brain, were only minor in rodent brains. Our study shows that oxidative injury and its triggering mechanisms diverge in different models of rodent central nervous system inflammation. The amplification of oxidative injury, which has been suggested in MS, is only reflected to a limited degree in the studied rodent models.     

Precision medicine in chronic disease management: The multiple sclerosis BioScreen

We present a precision medicine application developed for multiple sclerosis (MS): the MS BioScreen. This new tool addresses the challenges of dynamic management of a complex chronic disease; the interaction of clinicians and patients with such a tool illustrates the extent to which translational digital medicine—that is, the application of information technology to medicine—has the potential to radically transform medical practice. We introduce 3 key evolutionary phases in displaying data to health care providers, patients, and researchers: visualization (accessing data), contextualization (understanding the data), and actionable interpretation (real‐time use of the data to assist decision making). Together, these form the stepping stones that are expected to accelerate standardization of data across platforms, promote evidence‐based medicine, support shared decision making, and ultimately lead to improved outcomes. Ann Neurol 2014;76:633–642     

Molecular cytogenetic aberrations in autosomal dominant polycystic kidney disease tissue

Autosomal dominant polycystic kidney disease (ADPKD) is a genetically heterogeneous disorder characterized by focal cyst formation from any part of the nephron. The molecular bases include germinal mutation of either PKD1 or PKD2 genes, enhanced expression of several protooncogenes, alteration of the TGF-alpha/EGF/EGF receptor (EGFR) axis, and disturbed regulation of proliferative/apoptosis pathways. To identify new locations of ADPKD related oncogenes and/or tumor suppressor genes (TSG), comparative genomic hybridization (CGH) and loss of heterozygosity (LOH) analyses were performed for a series of individual cysts (n = 24) from eight polycystic kidneys. By CGH, imbalances were detected predominantly on chromosomes 1p, 9q, 16p, 19, and 22q in all tissues. DNA copy number gain was seen on chromosomes 3q and 4q in five samples. The CGH data were supplemented by LOH analysis using 83 polymorphic microsatellite markers distributed along chromosomes 1, 9, 16, 19, and 22. The highest frequency of LOH was found on the 1p35-36 and 16p13.3 segments in cysts from seven samples. Allelic losses on 9q were detected in six, whereas deletions at 19p13 and 22q11 bands were observed in three polycystic kidneys. These results indicate that the deleted chromosomal regions may contain genes important in ADPKD initiation and progression.