Measuring executive function in sheep (Ovis aries) using visual stimuli in a semi-automated operant system.

BACKGROUND: Cognitive impairment is a distinguishing feature of many neurodegenerative diseases. The intra-dimensional (ID) extra-dimensional (ED) attentional set shift task is part of a clinical battery of tests used to evaluate executive function in Huntington's and Alzheimer's disease patients. The IDED task, however, has not translated well to pre-clinical rodent models of neurological disease. NEW METHOD: The ability to perform executive tasks coupled with a long lifespan makes sheep (Ovis aries) an ideal species for modelling cognitive decline in progressive neurodegenerative conditions. We describe the methodology for testing the performance of sheep in the IDED task using a semi-automated system in which visual stimuli are presented as coloured letters on computer screens. RESULTS: During each stage of IDED testing, all sheep (n = 12) learned successfully to discriminate between different colours and letters. Sheep were quick to learn the rules of acquisition at each stage. They required significantly more trials to reach criterion (p < 0.05) and made more errors (p < 0.05) following stimulus reversal, with the exception of the ED shift (p > 0.05). COMPARISON WITH EXISTING METHOD(S): Previous research shows that sheep can perform IDED set shifting in a walk-through maze using solid objects with two changeable dimensions (colour and shape) as the stimuli. Presenting the stimuli on computer screens provides better validity, greater task flexibility and higher throughput than the walk-through maze. CONCLUSION: All sheep completed each stage of the task, with a range of abilities expected in an outbred population. The IDED task described is ideally suited as a quantifiable and clinically translatable measure of executive function in sheep.

Altered subcortical emotional salience processing differentiates Parkinson's patients with and without psychotic symptoms.

OBJECTIVE: Current research does not provide a clear explanation for why some patients with Parkinson's Disease (PD) develop psychotic symptoms. The 'aberrant salience hypothesis' of psychosis has been influential and proposes that dopaminergic dysregulation leads to inappropriate attribution of salience to irrelevant/non-informative stimuli, facilitating the formation of hallucinations and delusions. The aim of this study is to investigate whether non-motivational salience is altered in PD patients and possibly linked to the development of psychotic symptoms. METHODS: We investigated salience processing in 14 PD patients with psychotic symptoms, 23 PD patients without psychotic symptoms and 19 healthy controls. All patients were on dopaminergic medication for their PD. We examined emotional salience using a visual oddball fMRI paradigm that has been used to investigate early stages of schizophrenia spectrum psychosis, controlling for resting cerebral blood flow as assessed with arterial spin labelling fMRI. RESULTS: We found significant differences between patient groups in brain responses to emotional salience. PD patients with psychotic symptoms had enhanced brain responses in the striatum, dopaminergic midbrain, hippocampus and amygdala compared to patients without psychotic symptoms. PD patients with psychotic symptoms showed significant correlations between the levels of dopaminergic drugs they were taking and BOLD signalling, as well as psychotic symptom scores. CONCLUSION: Our study suggests that enhanced signalling in the striatum, dopaminergic midbrain, the hippocampus and amygdala is associated with the development of psychotic symptoms in PD, in line with that proposed in the 'aberrant salience hypothesis' of psychosis in schizophrenia.