Neuropsychological tests

2.4.1. National Adult Reading Test (NART)

All participants completed the National Adult Reading Test (Nelson et al. 1991), which is a reading-based estimate of IQ. It provides information regarding the premorbid IQ and is therefore well suited to account for differences in cognitive performance that are due to education rather than disease process. The NART was used to check whether the groups used in the individual studies were comparable in terms of their IQ. The procedure of this test requires that participants pronounce irregularly spelt words from a standardized written list (See Appendix 4 for the list of words and their correct pronunciation). The scores are then calculated on the basis of the number of correctly pronounced words.

2.4.2. N-back task

The N-back task is one of the most commonly used tests to probe working memory (Gevins et al. 1993). Abnormal performance on this task has classically been linked to prefrontal cortex dysfunction (Owen et al. 2005). In Chapters 4 and 5, N-back was used to probe the sensitivity of working memory paradigms to the schizotypy phenotype and the effects of drugs potentially affecting cognition.

In this task, participants were required to monitor a stream of visually presented stimuli that appeared on a computer screen and were required to respond whenever the stimulus on-screen was the same as the one shown N trials previously. N is an integer that could have been either 1, 2 or 3 and was specified at the beginning of each trial (Figure 2.1). In order to test whether participants were paying attention to the task, there were also trials in which they needed to respond whenever a specific letter was onscreen (“X”). See Appendix 5 for a full description of the N-back task reported in Chapters 4 and 5.

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Figure 2.1. N-back task. Participants indicated by pressing a mouse button whenever the letter on screen was the same as the letter presented 1, 2 or 3 screens before (1-, 2- and 3-back respectively).

2.4.3. Spatial Working Memory (SWM) task

This computerized task was reported in Chapters 4 and 5 as a measure of spatial working memory. It corresponds to the Maryland LNS spatial working memory task from the MATRICS cognitive battery (Nuechterlein et al. 2008). Similarly to the N- back task, abnormal results are also classically interpreted as an indication of prefrontal cortex dysfunction (Lee et al. 2005).

In the SWM task, volunteers were presented with a number of treasure chests on a computer screen. The participants had to search for coins in the treasure chests using the mouse with only one treasure chest containing a coin at any one time (Figure 2.2). Once a coin had been found, it would move to another chest but never to a chest where it had already been within the current trial. The task had 3 levels of difficulty (trials with 4, 6 and 8 chests). See Appendix 5 for a full description of the SWM task reported in Chapters 4 and 5.

See also Chapter 3 for a discussion of the relevance of working memory paradigms (such as the N-back and SWM tasks) as biomarkers of schizophrenia.

D

_N

A

A

B

_G

F

_G

S

_P

Y

S

1-back

2-back

3-back

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Figure 2.2. Spatial Working Memory (SWM) task. Participants searched treasure chests for coins with only one treasure chest containing a coin at any one time. Within the trial coins were never found twice in the same chest. Discovered coins mounted up on the right of the screen as shown on the figure to guide the participant on the

number of remaining coins.

2.4.4. Verbal Fluency (VF) task

This pen-and-paper task was used to test verbal fluency in Chapters 4 and 5. Abnormal performance on variations of this task has also been linked to abnormal prefrontal cortex activation (Curtis et al. 1998).

This thesis used a version of the VF task in which participants had to name as many words either beginning with a letter (F, A and S) or belonging to a category (animals and vegetables). There was also a condition in which two categories (fruit and furniture) were given and the participants had to alternate between them. See Appendix 5 for a full description of the VF task reported in Chapters 4 and 5.

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2.4.5. Salience Attribution Test (SAT)

The SAT was reported in Chapter 5 as a measure of aberrant salience attribution. This abnormality has been shown to correlate with psychotic symptoms in schizophrenia patients as wells as with the Introvertive Anhedonia OLIFE subscale score in healthy volunteers (Roiser et al. 2009). Functional MRI studies report reduced ventral striatal hemodynamic responses during reward cue conditions (Juckel et al. 2006;

Schlagenhauf et al. 2008) which has promoted suggestions that aberrant salience attribution may be an indicator of dysfunction in that brain region.

In the SAT coloured images of household objects or animals were presented prior to responding for possible rewards (money). One stimulus dimension (e.g. red vs. blue) very reliably predicted the availability or non-availability of money while the other (e.g. animals vs. household objects) was not a reliable predictor. If faster

responding/greater reward rating occurred to one of the irrelevant features over the other (e.g. animals faster over household objects), this indicated aberrant salience. See Appendix 6 for full description of the SAT and Chapter 3 for a discussion of its relevance as a biomarker of schizophrenia.

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Figure 2.3. Salience Attribution Test (SAT). The participants had to respond as quickly as possible to the presentation of a square in order to win possible reward. The stimulus was preceded by images that predicted the probability for reward. One of the dimensions of the stimulus was a good predictor (e.g. red vs. blue color) while another salient dimension was irrelevant (e.g. animals vs. household objects). The figure is reproduced from Jonathan Roiser’s work e.g. (Roiser et al. 2009) with the permission of the author.

2.4.6. Working memory event-related potentials (WM ERP) task

The experiments featuring in Chapters 6, 7 and 8 employed a working memory task to elicit event-related electroencephalographic or EEG activity (event-related potentials and oscillations). A very similar version of the task had been used previously by Haenschel et al. in a sample of schizophrenia patients (Haenschel et al. 2007; Haenschel et al. 2009). They reported aberrant modulation of the EEG activity by WM load in patients relative to controls. These results indicate that the EEG correlates of perceptual dysfunctions in schizophrenia might be the result of dysfunctional coordination between higher-order brain structures, such as the prefrontal cortex, and the sensory cortex.

In the task featuring in the current thesis, the participants were required to remember images that were sequentially presented in series of one, two or three (Figure 2.4).

Page | 42 After a fixed delay period a target probe appeared on the screen and the participants had to indicate whether it was part of the initial sample set by pressing a button. Full description of the WM ERP task can be found in the method sections of Chapters 6, 7 and 8.

Figure 2.4. Working memory event-related potential task. During encoding one, two or three images were presented for 400 ms seconds each separated by an inter- stimulus interval of 600 ms. A delay period of 6 seconds ensued (maintenance phase). A target image then appeared and remained onscreen for 3 seconds and the

participants were required to indicate by pressing a button whether it was shown during the encoding phase or not (retrieval phase). An inter-stimulus interval of 1 second separated the trials.