Fetal testosterone influences sexually dimorphic gray matter in the human brain

In nonhuman species, testosterone is known to have permanent organizing effects early in life that predict later expression of sex differences in brain and behavior. However, in humans, it is still unknown whether such mechanisms have organizing effects on neural sexual dimorphism. In human males, we show that variation in fetal testosterone (FT) predicts later local gray matter volume of specific brain regions in a direction that is congruent with sexual dimorphism observed in a large independent sample of age-matched males and females from the NIH Pediatric MRI Data Repository. Right temporoparietal junction/posterior superior temporal sulcus (RTPJ/pSTS), planum temporale/parietal operculum (PT/PO), and posterior lateral orbitofrontal cortex (plOFC) had local gray matter volume that was both sexually dimorphic and predicted in a congruent direction by FT. That is, gray matter volume in RTPJ/pSTS was greater for males compared to females and was positively predicted by FT. Conversely, gray matter volume in PT/PO and plOFC was greater in females compared to males and was negatively predicted by FT. Subregions of both amygdala and hypothalamus were also sexually dimorphic in the direction of Male > Female, but were not predicted by FT. However, FT positively predicted gray matter volume of a non-sexually dimorphic subregion of the amygdala. These results bridge a long-standing gap between human and nonhuman species by showing that FT acts as an organizing mechanism for the development of regional sexual dimorphism in the human brain.

Pathogenic LRRK2 mutations do not alter gene expression in cell model systems or human brain tissue

Point mutations in LRRK2 cause autosomal dominant Parkinson's disease. Despite extensive efforts to determine the mechanism of cell death in patients with LRRK2 mutations, the aetiology of LRRK2 PD is not well understood. To examine possible alterations in gene expression linked to the presence of LRRK2 mutations, we carried out a case versus control analysis of global gene expression in three systems: fibroblasts isolated from LRRK2 mutation carriers and healthy, non-mutation carrying controls; brain tissue from G2019S mutation carriers and controls; and HEK293 inducible LRRK2 wild type and mutant cell lines. No significant alteration in gene expression was found in these systems following correction for multiple testing. These data suggest that any alterations in basal gene expression in fibroblasts or cell lines containing mutations in LRRK2 are likely to be quantitatively small. This work suggests that LRRK2 is unlikely to play a direct role in modulation of gene expression, although it remains possible that this protein can influence mRNA expression under pathogenic cicumstances.

First human hNT neurons patterned on parylene-C/silicon dioxide substrates: Combining an accessible cell line and robust patterning technology for the study of the pathological adult human brain

In this communication, we describe a new method which has enabled the first patterning of human neurons (derived from the human teratocarcinoma cell line (hNT)) on parylene-C/silicon dioxide substrates. We reveal the details of the nanofabrication processes, cell differentiation and culturing protocols necessary to successfully pattern hNT neurons which are each key aspects of this new method. The benefits in patterning human neurons on silicon chip using an accessible cell line and robust patterning technology are of widespread value. Thus, using a combined technology such as this will facilitate the detailed study of the pathological human brain at both the single cell and network level.

Cognitive influences on the affective representation of touch and the sight of touch in the human brain

We show that the affective experience of touch and the sight of touch can be modulated by cognition, and investigate in an fMRI study where top-down cognitive modulations of bottom-up somatosensory and visual processing of touch and its affective value occur in the human brain. The cognitive modulation was produced by word labels, 'Rich moisturizing cream' or 'Basic cream', while cream was being applied to the forearm, or was seen being applied to a forearm. The subjective pleasantness and richness were modulated by the word labels, as were the fMRI activations to touch in parietal cortex area 7, the insula and ventral striatum. The cognitive labels influenced the activations to the sight of touch and also the correlations with pleasantness in the pregenual cingulate/orbitofrontal cortex and ventral striatum. Further evidence of how the orbitofrontal cortex is involved in affective aspects of touch was that touch to the forearm [which has C fiber Touch (CT) afferents sensitive to light touch] compared with touch to the glabrous skin of the hand (which does not) revealed activation in the mid-orbitofrontal cortex. This is of interest as previous studies have suggested that the CT system is important in affiliative caress-like touch between individuals.

Umami: a delicious flavor formed by convergence of taste and olfactory pathways in the human brain

Umami taste is produced by glutamate acting on a fifth taste system. However, glutamate presented alone as a taste stimulus is not highly pleasant, and does not act synergistically with other tastes (sweet, salt, bitter and sour). We show here that when glutamate is given in combination with a consonant, savory, odour (vegetable), the resulting flavor can be much more pleasant. Moreover, we showed using functional brain imaging with fMRI that the glutamate taste and savory odour combination produced much greater activation of the medial orbitofrontal cortex and pregenual cingulate cortex than the sum of the activations by the taste and olfactory components presented separately. Supralinear effects were much less (and significantly less) evident for sodium chloride and vegetable odour. Further, activations in these brain regions were correlated with the pleasantness and fullness of the flavor, and with the consonance of the taste and olfactory components. Supralinear effects of glutamate taste and savory odour were not found in the insular primary taste cortex. We thus propose that glutamate acts by the nonlinear effects it can produce when combined with a consonant odour in multimodal cortical taste-olfactory convergence regions. We propose the concept that umami can be thought of as a rich and delicious flavor that is produced by a combination of glutamate taste and a consonant savory odour. Glutamate is thus a flavor enhancer because of the way that it can combine supralinearly with consonant odours in cortical areas where the taste and olfactory pathways converge far beyond the receptors.

K-Surfer: a KNIME extension for the management and analysis of Human brain MRI FreeSurfer/FSL data

Human brain imaging techniques, such as Magnetic Resonance Imaging (MRI) or Diffusion Tensor Imaging (DTI), have been established as scientific and diagnostic tools and their adoption is growing in popularity. Statistical methods, machine learning and data mining algorithms have successfully been adopted to extract predictive and descriptive models from neuroimage data. However, the knowledge discovery process typically requires also the adoption of pre-processing, post-processing and visualisation techniques in complex data workflows. Currently, a main problem for the integrated preprocessing and mining of MRI data is the lack of comprehensive platforms able to avoid the manual invocation of preprocessing and mining tools, that yields to an error-prone and inefficient process. In this work we present K-Surfer, a novel plug-in of the Konstanz Information Miner (KNIME) workbench, that automatizes the preprocessing of brain images and leverages the mining capabilities of KNIME in an integrated way. K-Surfer supports the importing, filtering, merging and pre-processing of neuroimage data from FreeSurfer, a tool for human brain MRI feature extraction and interpretation. K-Surfer automatizes the steps for importing FreeSurfer data, reducing time costs, eliminating human errors and enabling the design of complex analytics workflow for neuroimage data by leveraging the rich functionalities available in the KNIME workbench.

Combining Human and Machine Brains - Practical systems in information & control

In this paper a look is taken at how the use of implant technology can be used to either increase the range of the abilities of a human and/or diminish the effects of a neural illness, such as Parkinson's Disease. The key element is the need for a clear interface linking the human brain directly with a computer. The area of interest here is the use of implant technology, particularly where a connection is made between technology and the human brain and/or nervous system. Pilot tests and experimentation are invariably carried out apriori to investigate the eventual possibilities before human subjects are themselves involved. Some of the more pertinent animal studies are discussed here. The paper goes on to describe human experimentation, in particular that carried out by the author himself, which led to him receiving a neural implant which linked his nervous system bi-directionally with the internet. With this in place neural signals were transmitted to various technological devices to directly control them. In particular, feedback to the brain was obtained from the fingertips of a robot hand and ultrasonic (extra) sensory input. A view is taken as to the prospects for the future, both in the near term as a therapeutic device and in the long term as a form of enhancement.

Human-machine symbiosis overview

The interface between humans and technology is a rapidly changing field. In particular as technological methods have improved dramatically so interaction has become possible that could only be speculated about even a decade earlier. This interaction can though take on a wide range of forms. Indeed standard buttons and dials with televisual feedback are perhaps a common example. But now virtual reality systems, wearable computers and most of all, implant technology are throwing up a completely new concept, namely a symbiosis of human and machine. No longer is it sensible simply to consider how a human interacts with a machine, but rather how the human-machine symbiotic combination interacts with the outside world. In this paper we take a look at some of the recent approaches, putting implant technology in context. We also consider some specific practical examples which may well alter the way we look at this symbiosis in the future. The main area of interest as far as symbiotic studies are concerned is clearly the use of implant technology, particularly where a connection is made between technology and the human brain and/or nervous system. Often pilot tests and experimentation has been carried out apriori to investigate the eventual possibilities before human subjects are themselves involved. Some of the more pertinent animal studies are discussed briefly here. The paper however concentrates on human experimentation, in particular that carried out by the authors themselves, firstly to indicate what possibilities exist as of now with available technology, but perhaps more importantly to also show what might be possible with such technology in the future and how this may well have extensive social effects. The driving force behind the integration of technology with humans on a neural level has historically been to restore lost functionality in individuals who have suffered neurological trauma such as spinal cord damage, or who suffer from a debilitating disease such as lateral amyotrophic sclerosis. Very few would argue against the development of implants to enable such people to control their environment, or some aspect of their own body functions. Indeed this technology in the short term has applications for amelioration of symptoms for the physically impaired, such as alternative senses being bestowed on a blind or deaf individual. However the issue becomes distinctly more complex when it is proposed that such technology be used on those with no medical need, but instead who wish to enhance and augment their own bodies, particularly in terms of their mental attributes. These issues are discussed here in the light of practical experimental test results and their ethical consequences.

An attempt to extend human sensory capabilities by means of implant technology

In this paper an attempt is described to increase the range of human sensory capabilities by means of implant technology. The key aim is to create an additional sense by feeding signals directly to the human brain, via the nervous system rather than via a presently operable human sense. Neural implant technology was used to directly interface a human nervous system with a computer in a one off trial. The output from active ultrasonic sensors was then employed to directly stimulate the human nervous system. An experimental laboratory set up was used as a test bed to assess the usefulness of this sensory addition.

Linking human and machine brains

A look is taken here at how the use of implant technology is rapidly diminishing the effects of certain neural illnesses and distinctly increasing the range of abilities of those affected. An indication is given of a number of problem areas in which such technology has already had a profound effect, a key element being the need for a clear interface linking the human brain directly with a computer. In order to assess the possible opportunities, both human and animal studies are reported on. The main thrust of the paper is however a discussion of neural implant experimentation linking the human nervous system bi-directionally with the internet. With this in place neural signals were transmitted to various technological devices to directly control them, in some cases via the internet, and feedback to the brain was obtained from such as the fingertips of a robot hand, ultrasonic (extra) sensory input and neural signals directly from another human's nervous system. Consideration is given to the prospects for neural implant technology in the future, both in the short term as a therapeutic device and in the long term as a form of enhancement, including the realistic potential for thought communication potentially opening up commercial opportunities. Clearly though, an individual whose brain is part human - part machine can have abilities that far surpass those with a human brain alone. Will such an individual exhibit different moral and ethical values to those of a human.? If so, what effects might this have on society?

On linking human and machine brains

A look is taken here at how the use of implant technology is rapidly diminishing the effects of certain neural illnesses and distinctly increasing the range of abilities of those affected. An indication is given of a number of problem areas in which such technology has already had a profound effect, a key element being the need for a clear interface linking the human brain directly with a computer. In order to assess the possible opportunities, both human and animal studies are reported on. The main thrust of the paper is, however, a discussion of neural implant experimentation linking the human nervous system bi-directionally with the internet. With this in place, neural signals were transmitted to various technological devices to directly control them, in some cases via the internet, and feedback to the brain was obtained from, for example, the fingertips of a robot hand, and ultrasonic (extra) sensory input and neural signals directly from another human's nervous system. Consideration is given to the prospects for neural implant technology in the future, both in the short term as a therapeutic device and in the long term as a form of enhancement, including the realistic potential for thought communication-potentially opening up commercial opportunities. Clearly though, an individual whose brain is part human-part machine can have abilities that far surpass those with a human brain alone. Will such an individual exhibit different moral and ethical values from those of a human? If so, what effects might this have on society? (C) 2008 Elsevier B.V. All rights reserved.

Human frontal lobes are not relatively large

One of the most pervasive assumptions about human brain evolution is that it involved relative enlargement of the frontal lobes. We show that this assumption is without foundation. Analysis of five independent data sets using correctly scaled measures and phylogenetic methods reveals that the size of human frontal lobes, and of specific frontal regions, is as expected relative to the size of other brain structures. Recent claims for relative enlargement of human frontal white matter volume, and for relative enlargement shared by all great apes, seem to be mistaken. Furthermore, using a recently developed method for detecting shifts in evolutionary rates, we find that the rate of change in relative frontal cortex volume along the phylogenetic branch leading to humans was unremarkable and that other branches showed significantly faster rates of change. Although absolute and proportional frontal region size increased rapidly in humans, this change was tightly correlated with corresponding size increases in other areas andwhole brain size, and with decreases in frontal neuron densities. The search for the neural basis of human cognitive uniqueness should therefore focus less on the frontal lobes in isolation and more on distributed neural networks.

Patterning and detailed study of human hNT astrocytes on parylene-C/silicon dioxide substrates to the single cell level

It is estimated that the adult human brain contains 100 billion neurons with 5–10 times as many astrocytes. Although it has been generally considered that the astrocyte is a simple supportive cell to the neuron, recent research has revealed new functionality of the astrocyte in the form of information transfer to neurons of the brain. In our previous work we developed a protocol to pattern the hNT neuron (derived from the human teratocarcinoma cell line (hNT)) on parylene-C/SiO2 substrates. In this work, we report how we have managed to pattern hNT astrocytes, on parylene-C/SiO2 substrates to single cell resolution. This article disseminates the nanofabrication and cell culturing steps necessary for the patterning of such cells. In addition, it reports the necessary strip lengths and strip width dimensions of parylene-C that encourage high degrees of cellular coverage and single cell isolation for this cell type. The significance in patterning the hNT astrocyte on silicon chip is that it will help enable single cell and network studies into the undiscovered functionality of this interesting cell, thus, contributing to closer pathological studies of the human brain.

First human hNT astrocytes patterned to single cell resolution on parylene-C/Silicon dioxide substrates

In our previous work we developed a successful protocol to pattern the human hNT neuron (derived from the human teratocarcinoma cell line (hNT)) on parylene-C/SiO2 substrates. This communication, reports how we have successfully managed to pattern the supportive cell to the neuron, the hNT astrocyte, on such substrates. Here we disseminate the nanofabrication, cell differentiation and cell culturing protocols necessary to successfully pattern the first human hNT astrocytes to single cell resolution on parylene-C/SiO2 substrates. This is performed for varying parylene strip widths providing excellent contrast to the SiO2 substrate and elegant single cell isolation at 10μm strip widths. The breakthrough in patterning human cells on a silicon chip has widespread implications and is valuable as a platform technology as it enables a detailed study of the human brain at the cellular and network level.

Female-specific intergenerational transmission patterns of the human corticolimbic circuitry

Parents have large genetic and environmental influences on offspring’s cognition, behavior, and brain. These intergenerational effects are observed in mood disorders, with particularly robust association in depression between mothers and daughters. No studies have thus far examined the neural bases of these intergenerational effects in humans. Corticolimbic circuitry is known to be highly relevant in a wide range of processes including mood regulation and depression. These findings suggest that corticolimbic circuitry may also show matrilineal transmission patterns. We therefore examined human parent-offspring association in this neurocircuitry, and investigated the degree of association in gray matter volume between parent and offspring. We used voxel-wise correlation analysis in a total of 35 healthy families, consisting of parents and their biological offspring. We found positive associations of regional grey matter volume in the corticolimbic circuit including the amygdala, hippocampus, anterior cingulate cortex, and ventromedial prefrontal cortex between biological mothers and daughters. This association was significantly greater than mother-son, father-daughter, and father-son associations. The current study suggests that the corticolimbic circuitry, which has been implicated in mood regulation, shows a matrilineal specific transmission patterns. Our preliminary findings are consistent with what has been found behaviorally in depression, and may have clinical implications for disorders known to have dysfunction in mood regulation such as depression. Studies such as ours will likely bridge animal work examining gene expression in the brains and clinical symptom-based observations, and provide promising ways to investigate intergenerational transmission patterns in the human brain.