Neurobiological investigations of autism symptomatology and cerebellar pathology

The cerebellum is the most commonly reported brain region to demonstrate pathology in autism. Multiple reports have indicated a lower density of Purkinje cells (PCs) in the posterolateral cerebellar hemispheres. We performed a stereological technique to precisely quantify PCs in postmortem autism cases compared to age- and sex-matched controls. We found that although PC density was lower in all cerebellar regions studied, the most significant difference was in lobule VIIa of the posterior lobe. The PCs in this region project to deep cerebellar nuclei that reciprocally connect to all aspects of the established broader sensorimotor gating network. Sensorimotor gating abnormalities are commonly observed in individuals diagnosed with autism, and may contribute to problems with sensory processing and behavioral inhibition in these individuals. We studied a rat model of sensorimotor gating impairment, in which the histamine H1 receptor antagonist, pyrilamine, improved sensorimotor gating. Using autoradiography, we found that pyrilamine treatment altered H1 receptor and α7 nicotinic receptor binding in the anterior cingulate and insular cortex, respectively, an effect which correlated with improved sensorimotor gating. Histamine functions as both a neurotransmitter as well as a regulator of glial activity throughout the brain. Using western blots, we quantified H1 receptor levels in lobule VIIa from postmortem autism cases but found no difference compared to controls. We further quantified additional proteins to investigate theories of neuroimmune and neuroendocrine dysregulation in the cerebellum in autism. These included IBA-1, GFAP, IL-6, androgen receptor, estrogen receptor β, and aromatase. We found no evidence to support these theories: all protein levels tested were found to be similar in the autism and control groups. We suggest further studies to better understand cerebellar pathogenesis and regulation of sensorimotor gating in autism. The implications of sensorimotor gating impairment in autism are discussed in relation to the established symptomatology of this neurodevelopmental behavioral disorder

Consensus Paper: Radiological Biomarkers of Cerebellar Diseases

Hereditary and sporadic cerebellar ataxias represent a vast and still growing group of diseases whose diagnosis and differentiation cannot only rely on clinical evaluation. Brain imaging including magnetic resonance (MR) and nuclear medicine techniques allows for characterization of structural and functional abnormalities underlying symptomatic ataxias. These methods thus constitute a potential source of radiological biomarkers, which could be used to identify these diseases and differentiate subgroups of them, and to assess their severity and their evolution. Such biomarkers mainly comprise qualitative and quantitative data obtained from MR including proton spectroscopy, diffusion imaging, tractography, voxel-based morphometry, functional imaging during task execution or in a resting state, and from SPETC and PET with several radiotracers. In the current article, we aim to illustrate briefly some applications of these neuroimaging tools to evaluation of cerebellar disorders such as inherited cerebellar ataxia, fetal developmental malformations, and immune-mediated cerebellar diseases and of neurodegenerative or early-developing diseases, such as dementia and autism in which cerebellar involvement is an emerging feature. Although these radiological biomarkers appear promising and helpful to better understand ataxia-related anatomical and physiological impairments, to date, very few of them have turned out to be specific for a given ataxia with atrophy of the cerebellar system being the main and the most usual alteration being observed. Consequently, much remains to be done to establish sensitivity, specificity, and reproducibility of available MR and nuclear medicine features as diagnostic, progression and surrogate biomarkers in clinical routine

Preliminary Minimum Reporting Requirements for In-Vivo Neural Interface Research: I. Implantable Neural Interfaces

The pace of research and development in neuroscience, neurotechnology, and neurorehabilitation is rapidly accelerating, with the number of publications doubling every 4.2 years. Maintaining this progress requires technological standards and scientific reporting guidelines to provide frameworks for communication and interoperability. The present lack of such standards for neurotechnologies limits the transparency, reproducibility, and meta-analysis of this growing body of research, posing an ongoing barrier to research, clinical, and commercial objectives. Continued neurotechnological innovation requires the development of some minimal standards to promote integration between this broad spectrum of technologies and therapies. To preserve design freedom and accelerate the translation of research into safe and effective technologies with maximal user benefit, such standards must be collaboratively co-developed by a full spectrum of neuroscience and neurotechnology stakeholders. This paper summarizes the preliminary recommendations of IEEE Working Group P2794, developing a Reporting Standard for in-vivo Neural Interface Research (RSNIR). Index Terms— Neurotechnology, reproducibility, scientific reporting, standardization, bioelectronic medicine Impact Statement— This work provides a preliminary set of reporting guidelines for implantable neural interface research, developed by IEEE WG P2794 in open collaboration between a range of stakeholders to accelerate the research, development, and integration of innovative neurotechnologies

New Pond—Indicator Bacteria to Complement Routine Monitoring in a Wet/Dry Tropical Wastewater Stabilization System

Bacteria monitoring is a critical part of wastewater management. At tropical wastewater stabilization ponds (WSPs) in north Australia, sanitation is assessed using the standard fecal indicator bacteria (FIB) Escherichia coli and Enterococci. However, these bacteria are poor surrogates for enteric pathogens. A focus on FIB misses the majority of pond-bacteria and how they respond to the tropical environment. Therefore, we aimed to identify the unknown pond bacteria and indicators that can complement E. coli to improve monitoring. Over two years, we measured the bacterial community in 288 wastewater samples during the wet and dry seasons. The WSP community was spatially and temporally dynamic. Standard pond-water physicochemical measures like conductivity poorly explained these community shifts. Cyanobacteria represented >6% of the WSP bacterial population, regardless of sample timing and location. Fecal bacteria were abundant in the first pond. However, in downstream ponds, these bacteria were less abundant, and instead, environmental taxa were common. For each pond, we identified a bacterial fingerprint that included new candidate bacterial indicators of fecal waste and processes like nitrogen removal. Combining the new indicators with standard FIB monitoring represents a locally relevant approach to wastewater monitoring that facilitates new tests for human fecal pollution within tropical climates

Preliminary Minimum Reporting Requirements for Reporting In-Vivo Neural Interface Research: I. Implantable Neural Interfaces

The pace of research and development in neuroscience, neurotechnology, and neurorehabilitation is rapidly accelerating, with the number of publications doubling every 4.2 years. Maintaining this progress requires technological standards and scientific reporting guidelines to provide frameworks for communication and interoperability. The present lack of such standards for neurotechnologies limits the transparency, reproducibility, and meta-analysis of this growing body of research, posing an ongoing barrier to research, clinical, and commercial objectives. Continued neurotechnological innovation requires the development of some minimal standards to promote integration between this broad spectrum of technologies and therapies. To preserve design freedom and accelerate the translation of research into safe and effective technologies with maximal user benefit, such standards must be collaboratively co-developed by a full spectrum of neuroscience and neurotechnology stakeholders. This paper summarizes the preliminary recommendations of IEEE Working Group P2794, developing a Reporting Standard for in-vivo Neural Interface Research (RSNIR). Index Terms— Neurotechnology, reproducibility, scientific reporting, standardization, bioelectronic medicine Impact Statement— This work provides a preliminary set of reporting guidelines for implantable neural interface research, developed by IEEE WG P2794 in open collaboration between a range of stakeholders to accelerate the research, development, and integration of innovative neurotechnologies

Overall PC Density Decreases with Age.

<p>Overall PC density obtained from the anterior, posterior, and flocculonodular lobes negatively correlates with age (R² = −0.39±0.14, p = 0.030). Some cases were missing data from an individual region (as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081255#s2" target="_blank">Methods</a>) and were not included: one female and one male case from the autism and control groups were not included.</p

Models of PC Arrangement.

<p>These figures represent the importance of estimating PC density in 3-dimensional space rather than along a 1-dimensional line (PC/mm³ rather than PC/mm). 7a and 7b display two views of a 3-dimensional model of a cerebellar folium, in which PCs (black) are arranged in a monolayer apposed to the granule cell layer (blue) that surrounds a central white matter tract (white). 7b displays two slices, one perfectly parallel to a plane of PCs, and the other, more realistically, transverse to this plane. 7c and 7d are cartoons demonstrating the PC arrangement within the parallel and transverse slice, respectively. Notice in 7d the PC layer is thicker, the degree to which depends on the slice position. Also notice that the selection of which PCs lie perfectly along a line is ambiguous (a few examples have been circled in red). This ambiguity introduces human error when performing an estimate of PC/mm that is eliminated in 3-dimensional estimates of PC/mm³ as are utilized in this study.</p