Did you see that? Dissociating advanced visual information and ball flight constrains perception and action processes during one-handed catching

The integration of separate, yet complimentary, cortical pathways appears to play a role in visual perception and action when intercepting objects. The ventral system is responsible for object recognition and identification, while the dorsal system facilitates continuous regulation of action. This dual-system model implies that empirically manipulating different visual information sources during performance of an interceptive action might lead to the emergence of distinct gaze and movement pattern profiles. To test this idea, we recorded hand kinematics and eye movements of participants as they attempted to catch balls projected from a novel apparatus that synchronised or de-synchronised accompanying video images of a throwing action and ball trajectory. Results revealed that ball catching performance was less successful when patterns of hand movements and gaze behaviours were constrained by the absence of advanced perceptual information from the thrower's actions. Under these task constraints, participants began tracking the ball later, followed less of its trajectory, and adapted their actions by initiating movements later and moving the hand faster. There were no performance differences when the throwing action image and ball speed were synchronised or de-synchronised since hand movements were closely linked to information from ball trajectory. Results are interpreted relative to the two-visual system hypothesis, demonstrating that accurate interception requires integration of advanced visual information from kinematics of the throwing action and from ball flight trajectory.

Input from the amygdala to the rat nucleus accumbens : its relationship with tyrosine hydroxylase immunoreactivity and identified neurons.

Both tyrosine hydroxylase-positive fibres from the mesolimbic dopamine system and amygdala projection fibres from the basolateral nucleus are known to terminate heavily in the nucleus accumbens. Caudal amygdala fibres travelling dorsally via the stria terminalis project densely to the nucleus accumbens shell, especially in the dopamine rich septal hook. The amygdala has been associated with the recognition of emotionally relevant stimuli while the mesolimbic dopamine system is implicated with reward mechanisms. There is behavioural and electrophysiological evidence that the amygdala input to the nucleus accumbens is modulated by the mesolimbic dopamine input, but it is not known how these pathways interact anatomically within the nucleus accumbens. Using a variety of neuroanatomical techniques including anterograde and retrograde tracing, immunocytochemistry and intracellular filling, we have demonstrated convergence of these inputs on to medium-sized spiny neurons. The terminals of the basolateral amygdala projection make asymmetrical synapses predominantly on the heads of spines which also receive on their necks or adjacent dendrites, symmetrical synaptic input from the mesolimbic dopamine system. Some of these neurons have also been identified as projection neurons, possibly to the ventral pallidum. We have shown a synaptic level how dopamine is positioned to modulate excitatory limbic input in the nucleus accumbens.

A computational model for BMP movement in sea urchin embryos

Bone morphogen proteins (BMPs) are distributed along a dorsal-ventral (DV) gradient in many developing embryos. The spatial distribution of this signaling ligand is critical for correct DV axis specification. In various species, BMP expression is spatially localized, and BMP gradient formation relies on BMP transport, which in turn requires interactions with the extracellular proteins Short gastrulation/Chordin (Chd) and Twisted gastrulation (Tsg). These binding interactions promote BMP movement and concomitantly inhibit BMP signaling. The protease Tolloid (Tld) cleaves Chd, which releases BMP from the complex and permits it to bind the BMP receptor and signal. In sea urchin embryos, BMP is produced in the ventral ectoderm, but signals in the dorsal ectoderm. The transport of BMP from the ventral ectoderm to the dorsal ectoderm in sea urchin embryos is not understood. Therefore, using information from a series of experiments, we adapt the mathematical model of Mizutani et al. (2005) and embed it as the reaction part of a one-dimensional reaction–diffusion model. We use it to study aspects of this transport process in sea urchin embryos. We demonstrate that the receptor-bound BMP concentration exhibits dorsally centered peaks of the same type as those observed experimentally when the ternary transport complex (Chd-Tsg-BMP) forms relatively quickly and BMP receptor binding is relatively slow. Similarly, dorsally centered peaks are created when the diffusivities of BMP, Chd, and Chd-Tsg are relatively low and that of Chd-Tsg-BMP is relatively high, and the model dynamics also suggest that Tld is a principal regulator of the system. At the end of this paper, we briefly compare the observed dynamics in the sea urchin model to a version that applies to the fly embryo, and we find that the same conditions can account for BMP transport in the two types of embryos only if Tld levels are reduced in sea urchin compared to fly.

Morphometric modelling of ageing in the human pubic symphysis : sexual dimorphism in an Australian population

Despite the prominent use of the pubic symphysis for age estimation in forensic anthropology, little has been documented regarding the quantitative morphological and micro-architectural changes of this surface. Specifically, utilising post-mortem computed tomography data from a large, contemporary Australian adult population, this study aimed to evaluate sexual dimorphism in the morphology and bone composition of the symphyseal surface; and temporal characterisation of the pubic symphysis in individuals of advancing age. The sample consisted of multi-slice computed tomography (MSCT) scans of the pubic symphysis(slice thickness: 0.5 mm, overlap: 0.1 mm) of 200 individuals of Caucasian ancestry aged 15–70 years, obtained in 2011. Surface rendering reconstruction of the symphyseal surface was conducted in OsiriX1 (v.4.1) and quantitative analyses in Rapidform XOSTM and OsteomeasureTM. Morphometric variables including inter-pubic distance, surface area, circumference, maximum height and width of the symphyseal surface and micro-architectural assessment of cortical and trabecular bone compositions were quantified using novel automated engineering software capabilities. The major results of this study are correlated with the macroscopic ossification and degeneration pattern of the symphyseal surface, demonstrating significant age-related changes in the morphometric and bone tissue variables between 15 and 70 years. Regardless of sex, the overall dimensions of the symphyseal surface increased with age, coupled with a decrease in bone mass in the trabecular and cortical bone compartments. Significant differences between the ventral, dorsal and medial cortical surfaces were observed, which may be correlated to bone formation activity dependent on muscle activity and ligamentous attachments. Our study demonstrates significant sexual dimorphism at this site, with males exhibiting greater surface dimensions than females. These baseline results provide a detailed insight into the changes in the structure of the pubic symphysis with ageing and sexually dimorphic features associated with the cortical and trabecular bone profiles.

Varenicline decreases ethanol intake and increases dopamine release via neuronal nicotinic acetylcholine receptors in the nucleus accumbens

BACKGROUND AND PURPOSE Varenicline, a neuronal nicotinic acetylcholine receptor (nAChR) modulator, decreases ethanol consumption in rodents and humans. The proposed mechanism of action for varenicline to reduce ethanol consumption has been through modulation of dopamine (DA) release in the nucleus accumbens (NAc) via α4*-containing nAChRs in the ventral tegmental area (VTA). However, presynaptic nAChRs on dopaminergic terminals in the NAc have been shown to directly modulate dopaminergic signalling independently of neuronal activity from the VTA. In this study, we determined whether nAChRs in the NAc play a role in varenicline’s effects on ethanol consumption. EXPERIMENTAL APPROACH Rats were trained to consume ethanol using the intermittent-access two-bottle choice protocol for 10 weeks. Ethanol intake was measured after varenicline or vehicle was microinfused into the NAc (core, shell or core-shell border) or the VTA (anterior or posterior). The effect of varenicline treatment on DA release in the NAc was measured using both in vivo microdialysis and in vitro fast-scan cyclic voltammetry (FSCV). KEY RESULTS Microinfusion of varenicline into the NAc core and core-shell border, but not into the NAc shell or VTA, reduced ethanol intake following long-term ethanol consumption. During microdialysis, a significant enhancement in accumbal DA release occurred following systemic administration of varenicline and FSCV showed that varenicline also altered the evoked release of DA in the NAc. CONCLUSION AND IMPLICATIONS Following long-term ethanol consumption, varenicline in the NAc reduces ethanol intake, suggesting that presynaptic nAChRs in the NAc are important for mediating varenicline’s effects on ethanol consumption.

Orexin/hypocretin role in reward: implications for opioid and other addictions

Addiction is a devastating disorder that affects 15.3 million people worldwide. While prevalent, few effective treatments exist. Orexin receptors have been proposed as a potential target for anti-craving medications. Orexins, also known as hypocretins, are neuropeptides produced in neurons of the lateral and dorsomedial hypothalamus and perifornical area, which project widely throughout the brain. The absence of orexins in rodents and humans leads to narcolepsy. However, orexins also have an established role in reward seeking. This review will discuss some of the original studies describing the roles of the orexins in reward seeking as well as specific works that were presented at the 2013 International Narcotics Research Conference. Orexin signalling can promote drug-induced plasticity of glutamatergic synapses onto dopamine neurons of the ventral tegmental area (VTA), a brain region implicated in motivated behaviour. Additional evidence suggests that orexin signalling can also promote drug seeking by initiating an endocannabinoid-mediated synaptic depression of GABAergic inputs to the VTA, and thereby disinhibiting dopaminergic neurons. Orexin neurons co-express the inhibitory opioid peptide dynorphin. It has been proposed that orexin in the VTA may not mediate reward per se, but rather occludes the ‘anti-reward’ effects of dynorphin. Finally, orexin signalling in the prefrontal cortex and the central amygdala is implicated in reinstatement of reward seeking. This review will highlight recent work describing the role of orexin signalling in cellular processes underlying addiction-related behaviours and propose novel hypotheses for the mechanisms by which orexin signalling may impart drug seeking.

Single voxel Magnetic Resonance Spectroscopic (1H-MRS) analysis of deep brain structures after traumatic prefrontal brain injury (TBI) in rat

Chronic difficulties arising from mild brain injury (TBI) are difficult to predict because the processes underlying changes after TBI are poorly understood. In mild brain injury the extent of neuropsychiatric and cognitive symptoms correspond poorly to overt tissue loss (Barth 1983; Liu 2010). Cellular, immune and hormonal cascades occurring after injury and continuing during the healing process may impact uninjured brain regions sensitive to the effects of physiological and emotional stress, which receive projections from the injury site. Changes in these most basic properties due to injury or disease have profound implications for virtually every aspect of brain function through disruption of neurotransmitter, neuroendocrine and metabolic systems. In order to screen for changes in transmitter and metabolic activity, in this study we developed Single voxel proton Magnetic Resonance Spectroscopy (1H-MRS) for use in both injured and control animals. We first evaluated if 1H-MRS could be used to evaluate in vivo, alterations in brain metabolism and catabolism of the prefrontal cortex, amygdala and ventral hippocampus in both control and injured animals after controlled cortical impact injury to the rat prefrontal cortex. We found that metabolite measurements for Myo-Inositol, Choline, creatine, Glutamate+Glutamine, and N-acetyl-acetate are attainable in deep brain structures in vivo in injured and controls rats. We next seek to evaluate longitudinally, in vivo, alterations in brain metabolism and catabolism of the prefrontal cortex, amygdala and ventral hippocampus during the first month after controlled cortical impact injury to the rat prefrontal cortex. These ongoing studies will provide data on the changes in transmitters and metabolites over time in injured and non-injured subjects. These studies address some of the fundamental questions about how mild brain injury has such diverse effects on overall brain health and function.

Biophysical correlates of intrinsic and stress-induced morphological variability in lateral amygdaloid neurons: A computational study

Morphological and physiological characteristics of neurons located in the dorsolateral and two ventral subdivisions of the lateral amygdala (LA) have been compared in order to differentiate their roles in the formation and storage of fear memories (Alphs et al, SfN abs 623.1, 2003). Briefly, in these populations, significant differences are observed in input resistance, membrane time constant, firing frequency, dendritic tortuosity, numbers of primary dendrites, dendritic segments and dendritic nodes...

L-dopa modulates functional connectivity in striatal cognitive and motor networks: A double-blind placebo-controlled study

Functional connectivity (FC) analyses of resting-state fMRI data allow for the mapping of large-scale functional networks, and provide a novel means of examining the impact of dopaminergic challenge. Here, using a double-blind, placebo-controlled design, we examined the effect of L-dopa, a dopamine precursor, on striatal resting-state FC in 19 healthy young adults.Weexamined the FC of 6 striatal regions of interest (ROIs) previously shown to elicit networks known to be associated with motivational, cognitive and motor subdivisions of the caudate and putamen (Di Martino et al., 2008). In addition to replicating the previously demonstrated patterns of striatal FC, we observed robust effects of L-dopa. Specifically, L-dopa increased FC in motor pathways connecting the putamen ROIs with the cerebellum and brainstem. Although L-dopa also increased FC between the inferior ventral striatum and ventrolateral prefrontal cortex, it disrupted ventral striatal and dorsal caudate FC with the default mode network. These alterations in FC are consistent with studies that have demonstrated dopaminergic modulation of cognitive and motor striatal networks in healthy participants. Recent studies have demonstrated altered resting state FC in several conditions believed to be characterized by abnormal dopaminergic neurotransmission. Our findings suggest that the application of similar experimental pharmacological manipulations in such populations may further our understanding of the role of dopaminergic neurotransmission in those conditions.

Selectivity of human retinotopic visual cortex to S-cone-opponent, L/M-cone-opponent and achromatic stimulation

Our aim was to make a quantitative comparison of the response of the different visual cortical areas to selective stimulation of the two different cone-opponent pathways [long- and medium-wavelength (L/M)- and short-wavelength (S)-cone-opponent] and the achromatic pathway under equivalent conditions. The appropriate stimulus-contrast metric for the comparison of colour and achromatic sensitivity is unknown, however, and so a secondary aim was to investigate whether equivalent fMRI responses of each cortical area are predicted by stimulus contrast matched in multiples of detection threshold that approximately equates for visibility, or direct (cone) contrast matches in which psychophysical sensitivity is uncorrected. We found that the fMRI response across the two colour and achromatic pathways is not well predicted by threshold-scaled stimuli (perceptual visibility) but is better predicted by cone contrast, particularly for area V1. Our results show that the early visual areas (V1, V2, V3, VP and hV4) all have robust responses to colour. No area showed an overall colour preference, however, until anterior to V4 where we found a ventral occipital region that has a significant preference for chromatic stimuli, indicating a functional distinction from earlier areas. We found that all of these areas have a surprisingly strong response to S-cone stimuli, at least as great as the L/M response, suggesting a relative enhancement of the S-cone cortical signal. We also identified two areas (V3A and hMT+) with a significant preference for achromatic over chromatic stimuli, indicating a functional grouping into a dorsal pathway with a strong magnocellular input.

Identifying rate-limiting nodes in large-scale cortical networks for visuospatial processing: An illustration using fMRI

With the advent of functional neuroimaging techniques, in particular functional magnetic resonance imaging (fMRI), we have gained greater insight into the neural correlates of visuospatial function. However, it may not always be easy to identify the cerebral regions most specifically associated with performance on a given task. One approach is to examine the quantitative relationships between regional activation and behavioral performance measures. In the present study, we investigated the functional neuroanatomy of two different visuospatial processing tasks, judgement of line orientation and mental rotation. Twenty-four normal participants were scanned with fMRI using blocked periodic designs for experimental task presentation. Accuracy and reaction time (RT) to each trial of both activation and baseline conditions in each experiment was recorded. Both experiments activated dorsal and ventral visual cortical areas as well as dorsolateral prefrontal cortex. More regionally specific associations with task performance were identified by estimating the association between (sinusoidal) power of functional response and mean RT to the activation condition; a permutation test based on spatial statistics was used for inference. There was significant behavioral-physiological association in right ventral extrastriate cortex for the line orientation task and in bilateral (predominantly right) superior parietal lobule for the mental rotation task. Comparable associations were not found between power of response and RT to the baseline conditions of the tasks. These data suggest that one region in a neurocognitive network may be most strongly associated with behavioral performance and this may be regarded as the computationally least efficient or rate-limiting node of the network.

Fear memory reactivation after extinction activates plasticity in the lateral amygdala

Little is known about the neuronal changes that occur within the lateral amygdala (LA) following fear extinction. In fear extinction, the repeated presentation of a conditioned stimulus (CS), in the absence of a previously paired aversive unconditioned stimulus (US), reduces fear elicited by the CS. Fear extinction is an active learning process that leads to the formation of a consolidated extinction memory, however it is fragile and prone to spontaneous recovery and renewal under environmental changes such as context. Understanding the neural mechanisms underlying fear extinction is of great clinical relevance, as psychological treatments of several anxiety disorders rely largely on extinction-based procedures and relapse is major clinical problem. This study investigated plasticity in the LA following fear memory reactivation in rats with and without extinction training. Phosphorylated MAPK (p44/42 ERK/MAPK), a protein kinase required in the amygdala for fear learning and its extinction, was used as a marker for neuronal plasticity. Rats (N = 11) underwent a Pavlovian auditory fear conditioning and extinction paradigm, and later received a single conditioned stimulus presentation to reactivate the fear memory. Results showed more pMAPK+ expressing neurons in the LA following extinction-reactivation compared to control rats, with the largest number of pMAPK+ neurons counted in the ventral LA, especially including the ventro-lateral subdivision (LAvl). These findings indicate that LA subdivision specific plasticity occurs to the conditioned fear memory in the LAvl following extinction-reactivation. These findings provide important insight into the organisation of fear memories in the LA, and pave the way for future research in the memory mechanisms of fear extinction and its pathophysiology.

Functional localization of the human color center by decreased water displacement using diffusion-weighted fMRI

Introduction Decreased water displacement following increased neural activity has been observed using diffusion-weighted functional MRI (DfMRI) at high b-values. The physiological mechanisms underlying the diffusion signal change may be unique from the standard blood oxygenation level-dependent (BOLD) contrast and closer to the source of neural activity. Whether DfMRI reflects neural activity more directly than BOLD outside the primary cerebral regions remains unclear. Methods Colored and achromatic Mondrian visual stimuli were statistically contrasted to functionally localize the human color center Area V4 in neurologically intact adults. Spatial and temporal properties of DfMRI and BOLD activation were examined across regions of the visual cortex. Results At the individual level, DfMRI activation patterns showed greater spatial specificity to V4 than BOLD. The BOLD activation patterns were more prominent in the primary visual cortex than DfMRI, where activation was localized to the ventral temporal lobe. Temporally, the diffusion signal change in V4 and V1 both preceded the corresponding hemodynamic response, however the early diffusion signal change was more evident in V1. Conclusions DfMRI may be of use in imaging applications implementing cognitive subtraction paradigms, and where highly precise individual functional localization is required.

Autosomal dominant spondylocostal dysostosis is caused by mutation in TBX6

In humans, congenital spinal defects occur with an incidence of 0.5-1 per 1000 live births. One of the most severe syndromes with such defects is spondylocostal dysostosis (SCD). Over the past decade, the genetic basis of several forms of autosomal recessive SCD cases has been solved with the identification of four causative genes (DLL3, MESP2, LFNG and HES7). Autosomal dominant forms of SCD have also been reported, but to date no genetic etiology has been described for these. Here, we have used exome capture and next-generation sequencing to identify a stoploss mutation in TBX6 that segregates with disease in two generations of one family. We show that this mutation has a deleterious effect on the transcriptional activation activity of the TBX6 protein, likely due to haploinsufficiency. In mouse, Tbx6 is essential for the patterning of the vertebral precursor tissues, somites; thus, mutation of TBX6 is likely to be causative of SCD in this family. This is the first identification of the genetic cause of an autosomal dominant form of SCD, and also demonstrates the potential of exome sequencing to identify genetic causes of dominant diseases even in small families with few affected individuals.

Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's Esophagus

Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (P combined = 4.09 × 10-9; odds ratio (OR) = 1.21, 95% confidence interval (CI) =1.13-1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (P combined = 2.74 × 10-10; OR = 1.14, 95% CI = 1.10-1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus. © 2012 Nature America, Inc. All rights reserved.