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Liverpool, Australia

Todd J.,University of Newcastle | Todd J.,Schizophrenia Research Institute | Michie P.T.,University of Newcastle | Michie P.T.,Schizophrenia Research Institute | And 6 more authors.
International Journal of Psychophysiology | Year: 2012

The model of mismatch negativity (MMN) as a simple index of change detection has been superseded by a richer understanding of how this event-related potential (ERP) reflects the representation of the sound environment in the brain. Our conceptualization of why the MMN is altered in certain groups must also evolve along with a better understanding of the activities reflected by this component. The detection of change incorporates processes enabling an automatic registration of "sameness", a memory for such regularities and the application of this recent acoustic context to interpreting the present and future state of the environment. It also includes "weighting" the importance of this change to an organism's behaviour. In this light, the MMN has been considered a prediction error signal that occurs when the brain detects that the present state of the world violates a context-driven expectation about the environment. In this paper we revisit the consistent observation of reduced MMN amplitude in patients with schizophrenia. We review existing data to address whether the apparent deficit might reflect problems in prediction error generation, estimation or salience. Possible interpretations of MMN studies in schizophrenia are linked to dominant theories about the neurobiology of the illness. © 2011 Elsevier B.V.

Shine J.M.,University of Sydney | Ward P.B.,University of New South Wales | Ward P.B.,Schizophrenia Research Unit | Naismith S.L.,University of Sydney | And 2 more authors.
Journal of Clinical Neuroscience | Year: 2011

Despite being common, the pathophysiological mechanisms underlying the phenomenon of freezing in patients with Parkinson's disease (PD) remain poorly understood. Recent work has shown that freezing behaviour can be provoked through the use of a computer-based virtual reality task, allowing for the exploration of freezing with functional MRI (fMRI). This article describes a single patient with PD who performed a virtual-reality walking task, both "On" and "Off" dopaminergic medication, while fMRI data were obtained. The results showed distinct BOLD patterns during "walking", "dual-task walking" and during episodes of freezing. The results of this single study highlight the potential utility of this approach in elucidating the underlying neural correlate of freezing behaviour in PD. Crown Copyright © 2011 Published by Elsevier Ltd. All rights reserved.

Kaur M.,University of Sydney | Battisti R.A.,University of Sydney | Lagopoulos J.,University of Sydney | Ward P.B.,University of New South Wales | And 3 more authors.
Journal of Psychiatry and Neuroscience | Year: 2012

Background: Mismatch negativity (MMN) and P3a are event-related potentials that index deviance detection and the orienting response, respectively. We have previously shown that the MMN/P3a complex is impaired in patients with schizophrenia and affective spectrum psychoses, which suggests that it may index a common pathophysiology and argues against the purported specificity in schizophrenia. Further research is warranted to determine whether patients with bipolar-spectrum disorders show similar impairments in these biomarkers. Methods: We assessed patients aged 15-30 years with early schizophrenia-spectrum disorders (schizophrenia, schizoaffective disorder, schizophreniform disorder), early bipolar-spectrum disorders (bipolar I or II, with and without psychotic features) and healthy, matched controls. We acquired MMN/P3a amplitudes during a 2-tone, auditory paradigm with 8% duration deviants. Clinical, psychosocial and neuropsychological assessments were also undertaken. Results: We included 20 patients with schizophrenia-spectrum disorders, 20 with bipolar-spectrum disorders and 20 controls in our study. Both patient groups showed significantly reduced frontocentral MMN and central P3a amplitudes. The schizophrenia-spectrum group had additional impairments in left temporal MMN and frontal P3a. Both patient groups performed worse than controls across psychosocial and clinical measures; however, only the schizophrenia-spectrum group performed significantly worse than controls for cognitive measures. Correlational analyses between patient groups revealed associations between frontocentral or left temporal MMN and psychiatric symptomatology or quality of life measures. Limitations: Limitations to our study include the modest sample size and the lack of control with regards to the effects of other (i.e., nonantipsychotic) psychotropic medications. Conclusion: Compared with patients in early stages of schizophrenia-spectrum disorders, those in the early stages of bipolar-spectrum disorders are similarly impaired in established biomarkers for schizophrenia. These findings support a shared diathesis model for psychotic and bipolar disorders. Furthermore, MMN/P3a may be a biomarker for a broader pathophysiology that overlaps traditional diagnostic clusters. © 2012 Canadian Medical Association.

Shine J.M.,University of Sydney | Matar E.,University of Sydney | Ward P.B.,University of New South Wales | Ward P.B.,Schizophrenia Research Unit | And 5 more authors.
Brain | Year: 2013

Freezing of gait is a devastating symptom of advanced Parkinson's disease yet the neural correlates of this phenomenon remain poorly understood. In this study, severity of freezing of gait was assessed in 18 patients with Parkinson's disease on a series of timed 'up and go' tasks, in which all patients suffered from episodes of clinical freezing of gait. The same patients also underwent functional magnetic resonance imaging with a virtual reality gait paradigm, performance on which has recently been shown to correlate with actual episodes of freezing of gait. Statistical parametric maps were created that compared the blood oxygen level-dependent response associated with paroxysmal motor arrests (freezing) to periods of normal motor output. The results of a random effects analysis revealed that these events were associated with a decreased blood oxygen level-dependent response in sensorimotor regions and an increased response within frontoparietal cortical regions. These signal changes were inversely correlated with the severity of clinical freezing of gait. Motor arrests were also associated with decreased blood oxygen level-dependent signal bilaterally in the head of caudate nucleus, the thalamus and the globus pallidus internus. Utilizing a mixed event-related/block design, we found that the decreased blood oxygen level-dependent response in the globus pallidus and the subthalamic nucleus persisted even after controlling for the effects of cognitive load, a finding which supports the notion that paroxysmal increases in basal ganglia outflow are associated with the freezing phenomenon. This method also revealed a decrease in the blood oxygen level-dependent response within the mesencephalic locomotor region during motor arrests, the magnitude of which was positively correlated with the severity of clinical freezing of gait. These results provide novel insights into the pathophysiology underlying freezing of gait and lend support to models of freezing of gait that implicate dysfunction across coordinated neural networks. © 2013 The Author (2013).

Neil A.L.,Menzies Research Institute | Carr V.J.,University of New South Wales | Carr V.J.,Schizophrenia Research Unit | Mihalopoulos C.,Deakin University | And 5 more authors.
Australian and New Zealand Journal of Psychiatry | Year: 2014

Objectives: To assess differences in costs of psychosis between the first and second Australian national surveys of psychosis and examine them in light of policy developments. Method: Cost differences due to changes in resource use and/or real price rises were assessed by minimizing differences in recruitment and costing methodologies between the two surveys. For each survey, average annual societal costs of persons recruited through public specialized mental health services in the census month were assessed through prevalence-based, bottom-up cost-of-illness analyses. The first survey costing methodology was employed as the reference approach. Unit costs were specific to each time period (2000, 2010) and expressed in 2010 Australian dollars. Results: There was minimal change in the average annual costs of psychosis between the surveys, although newly included resources in the second survey's analysis cost AUD$3183 per person. Among resources common to each analysis were significant increases in the average annual cost per person for ambulatory care of AUD$7380, nongovernment services AUD$2488 and pharmaceuticals AUD$1892, and an upward trend in supported accommodation costs. These increases were offset by over a halving of mental health inpatient costs of AUD$11,790 per person and a 84.6% (AUD$604) decrease in crisis accommodation costs. Productivity losses, the greatest component cost, changed minimally, reflecting the magnitude and constancy of reduced employment levels of individuals with psychosis across the surveys. Conclusions: Between 2000 and 2010 there was little change in total average annual costs of psychosis for individuals receiving treatment at public specialized mental health services. However, there was a significant redistribution of costs within and away from the health sector in line with government initiatives arising from the Second and Third National Mental Health Plans. Non-health sector costs are now a critical component of cost-of-illness analyses of mental illnesses reflecting, at least in part, a whole-of-government approach to care. © The Royal Australian and New Zealand College of Psychiatrists 2013.

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