Dr Renate Thienel

BACKGROUND: The PISA study aims to characterise the natural history and symptom progression of Alzheimer's disease (AD) at its prodromal phase. Utilising genetic risk prediction we have identified middle-aged and older Australians at high risk of dementia. In addition to onsite phenotyping, online surveys and cognitive testing have been used to economically collect information from an Australia-wide sample. METHOD: We have utilised our population based sample recruitment pool (N=15,351) of previous research participants who have been genome wide genotyped. Participants are invited to complete a comprehensive online survey, then complete online cognitive assessments, including Cambridge Brain Sciences (CBS), Cogstate, and an emotion recognition task. RESULT: Thus far nearly 4,000 participants have taken part in our online survey, and of these 2055 participants have completed the CBS assessment consisting of twelve subtests assessing memory, reasoning, attention, and planning. Recruitment for CBS and the other platforms is ongoing and participants are being invited to complete follow-up assessments after two years. At baseline we find significant association of both APOE genotype and polygenetic risk scores (PRS) for AD (omitting the APOE region) in healthy middle aged and elderly individuals with cognitive domains tested using the CBS platform. CONCLUSION: The utility of online cognitive testing for large scale testing in cohort and epidemiological studies will be discussed. The identification of cognitive changes associated with AD risk and prodromal disease gives important insights into mechanisms of AD development throughout the life span and is an opportunity to investigate prodromal markers to allow selection of individuals for early treatment strategies.

This study investigated neurodevelopmental changes in sound processing by recording mismatch negativity (MMN) in response to various degrees of sound complexity in 18 mildly to moderately autistic versus 15 healthy boys aged between 6 and 15¿years. Autistic boys presented with lower IQ and poor performance on a range of executive and social function measures when compared to their healthy counterparts. We found that MMN in response to duration deviants was less lateralized in the clinical group whereas larger amplitudes correlated with advanced age, thus capturing neurodevelopmental changes. Larger MMN in response to speech-like sound deviants was associated with better verbal fluency and executive function performance, respectively, but did not reliably discriminate the two groups.

Cognitive control involves both proactive and reactive processes. Paradigms that rely on reactive control have shown that frontoparietal oscillatory synchronization in the theta frequency band is associated with interference control. This study examines whether proactive control is also associated with connectivity in the same frontoparietal theta network or involves a distinct neural signature. A task-switching paradigm was used to differentiate between proactive and reactive control processes, involved in preparing to switch or repeat a task and resolving post-target interference, respectively. We confirm that reactive control is associated with frontoparietal theta connectivity. Importantly, we show that proactive control is also associated with theta band oscillatory synchronization but in a different frontoparietal network. These findings support the existence of distinct proactive and reactive cognitive control processes that activate different theta frontoparietal oscillatory networks.

Converging evidence from epidemiological, clinical and neuropsychological research suggests a link between cannabis use and increased risk of psychosis. Long-term cannabis use has also been related to deficit-like "negative" symptoms and cognitive impairment that resemble some of the clinical and cognitive features of schizophrenia. The current functional brain imaging study investigated the impact of a history of heavy cannabis use on impaired executive function in first-episode schizophrenia patients. Whilst performing the Tower of London task in a magnetic resonance imaging scanner, event-related blood oxygenation level-dependent (BOLD) brain activation was compared between four age and gender-matched groups: 12 first-episode schizophrenia patients; 17 long-term cannabis users; seven cannabis using first-episode schizophrenia patients; and 17 healthy control subjects. BOLD activation was assessed as a function of increasing task difficulty within and between groups as well as the main effects of cannabis use and the diagnosis of schizophrenia. Cannabis users and non-drug using first-episode schizophrenia patients exhibited equivalently reduced dorsolateral prefrontal activation in response to task difficulty. A trend towards additional prefrontal and left superior parietal cortical activation deficits was observed in cannabis-using first-episode schizophrenia patients while a history of cannabis use accounted for increased activation in the visual cortex. Cannabis users and schizophrenia patients fail to adequately activate the dorsolateral prefrontal cortex, thus pointing to a common working memory impairment which is particularly evident in cannabis-using first-episode schizophrenia patients. A history of heavy cannabis use, on the other hand, accounted for increased primary visual processing, suggesting compensatory imagery processing of the task.

Transcranial direct current stimulation (tDCS) is a non-invasive intervention altering neural plasticity by modulating neuronal excitability of pre- and postsynaptic neuron populations, which has been shown to improve depression symptoms and cognition. We investigated the effects of a single session of 20 min of 2 mA left-prefrontal anodal versus sham stimulation on auditory event-related potentials (ERPs) in 11 male and 5 female healthy subjects (mean age of 28.6 [SD 6.2] years) by employing a randomized single-blind crossover design. Stimulation effects on cortical glutamate (Glu) and glutamine (Glx) levels were subsequently measured in 12 of the 16 healthy subjects in a 3 T proton magnetic resonance spectroscopy scan. tDCS was associated with a significant increase of N1 amplitudes while smaller P3b amplitudes correlated with higher cortical Glu and Glx levels in the stimulated brain area when performing an auditory go/no-go discrimination task. tDCS did not change mismatch negativity, nor task performance or cortical Glu/Glx levels which, together with N1 amplitudes, depended on stimulation order ("sham" versus "active"). Increased N1 amplitudes are consistent with higher levels of cortical excitability following prefrontal anodal tDCS. The failure to replicate Glu/Glx changes with tDCS may have been masked by between-session carry-over effects while ceiling effects may have masked tDCS effects on task performance. © 2014 Elsevier GmbH. All rights reserved.

Background: 22q11.2 deletion syndrome (22q11DS) is associated with a number of physical anomalies and neuropsychological deficits including impairments in executive and sensorimotor function. It is estimated that 25% of children with 22q11DS will develop schizophrenia and other psychotic disorders later in life. Evidence of genetic transmission of information processing deficits in schizophrenia suggests performance in 22q11DS individuals will enhance understanding of the neurobiological and genetic substrates associated with information processing. In this report, we examine information processing in 22q11DS using measures of startle eyeblink modification and antisaccade inhibition to explore similarities with schizophrenia and associations with neurocognitive performance. Methods: Startle modification (passive and active tasks; 120- and 480-ms pre-pulse intervals) and antisaccade inhibition were measured in 25 individuals with genetically confirmed 22q11DS and 30 healthy control subjects. Results: Individuals with 22q1 1DS exhibited increased antisaccade error as well as some evidence (trend-level effect) of impaired sensorimotor gating during the active condition, suggesting a dysfunction in controlled attentional processing, rather than a pre-attentive dysfunction using this paradigm. Conclusions: The findings from the present study show similarities with previous studies in clinical populations associated with 22q11DS such as schizophrenia that may indicate shared dysfunction of inhibition pathways in these groups.

Cognitive impairment is one of the most significant factors determining the long-term rehabilitation prospects of schizophrenia patients. Cognitive training has been shown to be beneficial; however, effect sizes of cognitive remediation remain relatively low. Anodal transcranial direct current stimulation (tDCS) increases cortical excitability along with larger N1 auditory event-related potentials (ERPs), thus providing a non-invasive physiological mechanism that is potentially capable of facilitating cognitive training of schizophrenia patients. The current study investigated the effects of left-prefrontal anodal tDCS on auditory discrimination performance and N1, Mismatch Negativity (MMN), and P3b ERPs, which have been linked to cognitive and global function deficits in schizophrenia. We compared 20 min of 2 mA tDCS versus sham stimulation in 14 schizophrenia patients by employing a randomised crossover design. Patients performed equally well in a go/no-go auditory discrimination task when compared to healthy subjects but presented with significantly smaller N1, MMN and P3b amplitudes, which did not change with tDCS. Auditory discrimination performance and reaction times also remained unaffected by tDCS. Our findings suggest that a single application of tDCS has no acute effects on ERPs and associated auditory information processing in schizophrenia patients.

Attributions are constantly assigned in everyday life. A well-known phenomenon is the self-serving bias: that is, people's tendency to attribute positive events to internal causes (themselves) and negative events to external causes (other persons/circumstances). Here, we investigated the neural correlates of the cognitive processes implicated in self-serving attributions using social situations that differed in their emotional saliences. We administered an attributional bias task during fMRI scanning in a large sample of healthy subjects (n = 71). Eighty sentences describing positive or negative social situations were presented, and subjects decided via buttonpress whether the situation had been caused by themselves or by the other person involved. Comparing positive with negative sentences revealed activations of the bilateral posterior cingulate cortex (PCC). Self-attribution correlated with activation of the posterior portion of the precuneus. However, self-attributed positive versus negative sentences showed activation of the anterior portion of the precuneus, and self-attributed negative versus positive sentences demonstrated activation of the bilateral insular cortex. All significant activations were reported with a statistical threshold of p =.001, uncorrected. In addition, a comparison of our fMRI task with data from the Internal, Personal and Situational Attributions Questionnaire, Revised German Version, demonstrated convergent validity. Our findings suggest that the precuneus and the PCC are involved in the evaluation of social events with particular regional specificities: The PCC is activated during emotional evaluation, the posterior precuneus during attributional evaluation, and the anterior precuneus during self-serving processes. Furthermore, we assume that insula activation is a correlate of awareness of personal agency in negative situations. © 2013 Psychonomic Society, Inc.