Eye muscle proprioception is represented bilaterally in the sensorimotor cortex

The cortical representation of eye position is still uncertain. In the monkey a proprioceptive representation of the extraocular muscles (EOM) of an eye were recently found within the contralateral central sulcus. In humans, we have previously shown a change in the perceived position of the right eye after a virtual lesion with rTMS over the left somatosensory area. However, it is possible that the proprioceptive representation of the EOM extends to other brain sites, which were not examined in these previous studies. The aim of this fMRI study was to sample the whole brain to identify the proprioceptive representation for the left and the right eye separately. Data were acquired while passive eye movement was used to stimulate EOM proprioceptors in the absence of a motor command. We also controlled for the tactile stimulation of the eyelid by removing from the analysis voxels activated by eyelid touch alone. For either eye, the brain area commonly activated by passive and active eye movement was located bilaterally in the somatosensory area extending into the motor and premotor cytoarchitectonic areas. We suggest this is where EOM proprioception is processed. The bilateral representation for either eye contrasts with the contralateral representation of hand proprioception. We suggest that the proprioceptive representation of the two eyes next to each other in either somatosensory cortex and extending into the premotor cortex reflects the integrative nature of the eye position sense, which combines proprioceptive information across the two eyes with the efference copy of the oculomotor comman

Distribution of activity across the monkey cerebral cortical surface, thalamus and midbrain during rapid, visually guided saccades

To examine the distribution of visual and oculomotor activity across the macaque brain, we performed functional magnetic resonance imaging (fMRI) on awake, behaving monkeys trained to perform visually guided saccades. Two subjects alternated between periods of making saccades and central fixations while blood oxygen level dependent (BOLD) images were collected [3 T, (1.5 mm)(3) spatial resolution]. BOLD activations from each of four cerebral hemispheres were projected onto the subjects' cortical surfaces and aligned to a surface-based atlas for comparison across hemispheres and subjects. This surface-based analysis revealed patterns of visuo-oculomotor activity across much of the cerebral cortex, including activations in the posterior parietal cortex, superior temporal cortex and frontal lobe. For each cortical domain, we show the anatomical position and extent of visuo-oculomotor activity, including evidence that the dorsolateral frontal activation, which includes the frontal eye field (on the anterior bank of the arcuate sulcus), extends anteriorly into posterior principal sulcus (area 46) and posteriorly into part of dorsal premotor cortex (area 6). Our results also suggest that subcortical BOLD activity in the pulvinar thalamus may be lateralized during voluntary eye movements. These findings provide new neuroanatomical information as to the complex neural substrates that underlie even simple goal-directed behaviors

Will artificial intelligence eventually replace psychiatrists?

SUMMARY: The dystopian scenario of an 'artificial intelligence takeover' imagines artificial intelligence (AI) becoming the dominant form of intelligence on Earth, rendering humans redundant. As a society we have become increasingly familiar with AI and robots replacing humans in many tasks, certain jobs and even some areas of medicine, but surely this is not the fate of psychiatry?Here a computational neuroscientist (Janaina Mourão-Miranda) and psychiatrist (Justin Taylor Baker) suggest that psychiatry as a profession is relatively safe, whereas psychiatrists Christian Brown and Giles William Story predict that robots will be taking over the asylum

Thin current sheets in the deep geomagnetic tail

The ISEE‐3 magnetic field and plasma electron data from Jan ‐ March 1983 have been searched to study thin current sheets in the deep tail region. 33 events were selected where the spacecraft crossed through the current sheet from lobe to lobe within 15 minutes. The average thickness of the observed current sheets was 2.45R_{E}, and in 24 cases the current sheet was thinner than 3.0R_{E}; 6 very thin current sheets (thickness λ < 0.5R_{E}) were found. The electron data show that the very thin current sheets are associated with considerable temperature anisotropy. On average, the electron gradient current was ∼ 17% of the total current, whereas the current arising from the electron temperature anisotropy varied between 8 – 45% of the total current determined from the lobe field magnitude

Lysyl oxidase drives tumour progression by trapping EGF receptors at the cell surface

Lysyl oxidase (LOX) remodels the tumour microenvironment by cross-linking the extracellular matrix. LOX overexpression is associated with poor cancer outcomes. Here, we find that LOX regulates the epidermal growth factor receptor (EGFR) to drive tumour progression. We show that LOX regulates EGFR by suppressing TGFβ1 signalling through the secreted protease HTRA1. This increases the expression of Matrilin2 (MATN2), an EGF-like domain-containing protein that traps EGFR at the cell surface to facilitate its activation by EGF. We describe a pharmacological inhibitor of LOX, CCT365623, which disrupts EGFR cell surface retention and delays the growth of primary and metastatic tumour cells in vivo. Thus, we show that LOX regulates EGFR cell surface retention to drive tumour progression, and we validate the therapeutic potential of inhibiting this pathway with the small molecule inhibitor CCT365623

Vocal Communications and the Maintenance of Population Specific Songs in a Contact Zone

Bird song has been hypothesized to play a role in several important aspects of the biology of songbirds, including the generation of taxonomic diversity by speciation; however, the role that song plays in speciation within this group may be dependent upon the ability of populations to maintain population specific songs or calls in the face of gene flow and external cultural influences. Here, in an exploratory study, we construct a spatially explicit model of population movement to examine the consequences of secondary contact of populations singing distinct songs. We concentrate on two broad questions: 1) will population specific songs be maintained in a contact zone or will they be replaced by shared song, and 2) what spatial patterns in the distribution of songs may result from contact? We examine the effects of multiple factors including song-based mating preferences and movement probabilities, oblique versus paternal learning of song, and both cultural and genetic mutations. We find a variety of conditions under which population specific songs can be maintained, particularly when females have preferences for their population specific songs, and we document many distinct patterns of song distribution within the contact zone, including clines, banding, and mosaics

Selective Breeding for a Behavioral Trait Changes Digit Ratio

The ratio of the length of the second digit (index finger) divided by the fourth digit (ring finger) tends to be lower in men than in women. This 2D∶4D digit ratio is often used as a proxy for prenatal androgen exposure in studies of human health and behavior. For example, 2D∶4D ratio is lower (i.e. more “masculinized”) in both men and women of greater physical fitness and/or sporting ability. Lab mice have also shown variation in 2D∶4D as a function of uterine environment, and mouse digit ratios seem also to correlate with behavioral traits, including daily activity levels. Selective breeding for increased rates of voluntary exercise (wheel running) in four lines of mice has caused correlated increases in aerobic exercise capacity, circulating corticosterone level, and predatory aggression. Here, we show that this selection regime has also increased 2D∶4D. This apparent “feminization” in mice is opposite to the relationship seen between 2D∶4D and physical fitness in human beings. The present results are difficult to reconcile with the notion that 2D∶4D is an effective proxy for prenatal androgen exposure; instead, it may more accurately reflect effects of glucocorticoids, or other factors that regulate any of many genes

Decision Models and Technology Can Help Psychiatry Develop Biomarkers

Why is psychiatry unable to define clinically useful biomarkers? We explore this question from the vantage of data and decision science and consider biomarkers as a form of phenotypic data that resolves a well-defined clinical decision. We introduce a framework that systematizes different forms of phenotypic data and further introduce the concept of decision model to describe the strategies a clinician uses to seek out, combine, and act on clinical data. Though many medical specialties rely on quantitative clinical data and operationalized decision models, we observe that, in psychiatry, clinical data are gathered and used in idiosyncratic decision models that exist solely in the clinician's mind and therefore are outside empirical evaluation. This, we argue, is a fundamental reason why psychiatry is unable to define clinically useful biomarkers: because psychiatry does not currently quantify clinical data, decision models cannot be operationalized and, in the absence of an operationalized decision model, it is impossible to define how a biomarker might be of use. Here, psychiatry might benefit from digital technologies that have recently emerged specifically to quantify clinically relevant facets of human behavior. We propose that digital tools might help psychiatry in two ways: first, by quantifying data already present in the standard clinical interaction and by allowing decision models to be operationalized and evaluated; second, by testing whether new forms of data might have value within an operationalized decision model. We reference successes from other medical specialties to illustrate how quantitative data and operationalized decision models improve patient care

Reduction in Phencyclidine Induced Sensorimotor Gating Deficits in the Rat Following Increased System Xc − Activity in the Medial Prefrontal Cortex

Rationale: Aspects of schizophrenia, including deficits in sensorimotor gating, have been linked to glutamate dysfunction and/or oxidative stress in the prefrontal cortex. System xc −, a cystine–glutamate antiporter, is a poorly understood mechanism that contributes to both cellular antioxidant capacity and glutamate homeostasis. Objectives: Our goal was to determine whether increased system xc − activity within the prefrontal cortex would normalize a rodent measure of sensorimotor gating. Methods: In situ hybridization was used to map messenger RNA (mRNA) expression of xCT, the active subunit of system xc −, in the prefrontal cortex. Prepulse inhibition was used to measure sensorimotor gating; deficits in prepulse inhibition were produced using phencyclidine (0.3–3 mg/kg, sc). N-Acetylcysteine (10–100 μM) and the system xc − inhibitor (S)-4-carboxyphenylglycine (CPG, 0.5 μM) were used to increase and decrease system xc − activity, respectively. The uptake of 14C-cystine into tissue punches obtained from the prefrontal cortex was used to assay system xc − activity. Results: The expression of xCT mRNA in the prefrontal cortex was most prominent in a lateral band spanning primarily the prelimbic cortex. Although phencyclidine did not alter the uptake of 14C-cystine in prefrontal cortical tissue punches, intraprefrontal cortical infusion of N-acetylcysteine (10–100 μM) significantly reduced phencyclidine- (1.5 mg/kg, sc) induced deficits in prepulse inhibition. N-Acetylcysteine was without effect when coinfused with CPG (0.5 μM), indicating an involvement of system xc −. Conclusions: These results indicate that phencyclidine disrupts sensorimotor gating through system xc − independent mechanisms, but that increasing cystine–glutamate exchange in the prefrontal cortex is sufficient to reduce behavioral deficits produced by phencyclidine

The hypoxic cancer secretome induces pre-metastatic bone lesions through lysyl oxidase

Tumour metastasis is a complex process involving reciprocal interplay between cancer cells and host stroma at both primary and secondary sites, and is strongly influenced by microenvironmental factors such as hypoxia. Tumour-secreted proteins play a crucial role in these interactions and present strategic therapeutic potential. Metastasis of breast cancer to the bone affects approximately 85% of patients with advanced disease and renders them largely untreatable. Specifically, osteolytic bone lesions, where bone is destroyed, lead to debilitating skeletal complications and increased patient morbidity and mortality. The molecular interactions governing the early events of osteolytic lesion formation are currently unclear. Here we show hypoxia to be specifically associated with bone relapse in patients with oestrogen-receptor negative breast cancer. Global quantitative analysis of the hypoxic secretome identified lysyl oxidase (LOX) as significantly associated with bone-tropism and relapse. High expression of LOX in primary breast tumours or systemic delivery of LOX leads to osteolytic lesion formation whereas silencing or inhibition of LOX activity abrogates tumour-driven osteolytic lesion formation. We identify LOX as a novel regulator of NFATc1-driven osteoclastogenesis,independent of RANK ligand, which disrupts normal bone homeostasisleading to the formation of focal pre-metastatic lesions. We show that these lesions subsequently provide a platform for circulating tumour cells to colonize and form bone metastases. Our study identifies a novel mechanism of regulation of bone homeostasis and metastasis, opening up opportunities for novel therapeutic intervention with important clinical implications