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    [Show abstract] [Hide abstract] ABSTRACT: The non-competitive N-methyl-D-aspartate receptor antagonist ketamine leads to transient psychosis-like symptoms and impairments in oculomotor performance in healthy volunteers. This study examined whether the adverse effects of ketamine on oculomotor performance can be reversed by the atypical antipsychotic risperidone. In this randomized double-blind, placebo-controlled study, 72 healthy participants performed smooth pursuit eye movements (SPEM), prosaccades (PS) and antisaccades (AS) while being randomly assigned to one of four drug groups (intravenous 100 ng ml(-1) ketamine, 2 mg oral risperidone, 100 ng ml(-1) ketamine plus 2 mg oral risperidone, placebo). Drug administration did not lead to harmful adverse events. Ketamine increased saccadic frequency and decreased velocity gain of SPEM (all P<0.01) but had no significant effects on PS or AS (all P0.07). An effect of risperidone was observed for amplitude gain and peak velocity of PS and AS, indicating hypometric gain and slower velocities compared with placebo (both P0.04). No ketamine by risperidone interactions were found (all P0.26). The results confirm that the administration of ketamine produces oculomotor performance deficits similar in part to those seen in schizophrenia. The atypical antipsychotic risperidone did not reverse ketamine-induced deteriorations. These findings do not support the cognitive enhancing potential of risperidone on oculomotor biomarkers in this model system of schizophrenia and point towards the importance of developing alternative performance-enhancing compounds to optimise pharmacological treatment of schizophrenia.
    Full-text · Article · Dec 2013 · Translational Psychiatry
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    [Show abstract] [Hide abstract] ABSTRACT: The anterior insula (AI) plays a key role in affective processing, and insular dysfunction has been noted in several clinical conditions. Real-time functional MRI neurofeedback (rtfMRI-NF) provides a means of helping people learn to self-regulate activation in this brain region. Using the Blood Oxygenated Level Dependant (BOLD) signal from the right AI (RAI) as neurofeedback, we trained participants to increase RAI activation. In contrast, another group of participants were shown 'control' feedback from another brain area. Pre- and post- training affective probes were shown, with subjective ratings and skin conductance response (SCR) measured. We also investigated a reward-related reinforcement learning model of rtfMRI-NF In contrast to controls, we hypothesised a positive linear increase in RAI activation in participants shown feedback from this region, alongside increases in valence ratings and skin conductance response (SCR) to affective probes. Hypothesis-driven analyses showed a significant interaction between the RAI / control neurofeedback groups and the effect of self-regulation. Whole-brain analyses revealed a significant linear increase in RAI activation across four training runs in the group who received feedback from RAI. Increased activation was also observed in the caudate body and thalamus, likely representing feedback-related learning. No positive linear trend was observed in the RAI in the group receiving control feedback, suggesting that these data are not a general effect of cognitive strategy or control feedback. The control group did, however, show diffuse activation across the putamen, caudate and posterior insula which may indicate the representation of false feedback. No significant training-related behavioural differences were observed for valence ratings, or SCR. In addition, correlational analyses based on a reinforcement learning model showed the dorsal anterior cingulate cortex underpinned learning in both groups. In summary, these data demonstrate that it is possible to regulate the RAI using rtfMRI-NF within one scanning session, and that such reward-related learning is mediated by the dorsal anterior cingulate.
    Full-text · Article · Nov 2013 · NeuroImage
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    [Show abstract] [Hide abstract] ABSTRACT: Diffusion tensor imaging (DTI) methods are widely used to reconstruct white matter trajectories and to quantify tissue changes using the average diffusion properties of each brain voxel. Spherical deconvolution (SD) methods have been developed to overcome the limitations of the diffusion tensor model in resolving crossing fibers and to improve tractography reconstructions. However, the use of SD methods to obtain quantitative indices of white matter integrity has not been extensively explored. In this study, we show that the hindrance modulated orientational anisotropy (HMOA) index, defined as the absolute amplitude of each lobe of the fiber orientation distribution, can be used as a compact measure to characterize the diffusion properties along each fiber orientation in white matter regions with complex organization. We demonstrate that the HMOA is highly sensitive to changes in fiber diffusivity (e.g., myelination processes or axonal loss) and to differences in the microstructural organization of white matter like axonal diameter and fiber dispersion. Using simulations to describe diffusivity changes observed in normal brain development and disorders, we observed that the HMOA is able to identify white matter changes that are not detectable with conventional DTI indices. We also show that the HMOA index can be used as an effective threshold for in vivo data to improve tractography reconstructions and to better map white matter complexity inside the brain. In conclusion, the HMOA represents a true tract-specific and sensitive index and provides a compact characterization of white matter diffusion properties with potential for widespread application in normal and clinical populations. Hum Brain Mapp, 2012. © 2012 Wiley Periodicals, Inc.
    Full-text · Article · Oct 2013 · Human Brain Mapping
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