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Propagation of hippocampal activity in ultra-high risk schizophrenia psychosis subjects using Independent Component Analysis

A pilot study

Master's Thesis 2017 49 Pages

Psychology - Clinic and Health Psychology, Abnormal Psychology

Excerpt

Table of Contents

Abstract

Introduction
Schizophrenia and Visual Working Memory
Ultra-High-Risk of psychosis
Ultra-High-Risk of psychosis and Visual Working Memory
Hippocampus and Visual Working Memory
Hippocampal Impairments in Schizophrenia
The P300 event related potential
P300 Impairments in Schizophrenia
The P300 as a putative biomarker of psychosis risk
Detecting hippocampal activity through scalp EEG
Rationale, Aims and Hypotheses

Methods
Participants
Pilot study sample
PSYSCAN study sample
Inclusion and exclusion criteria
Ethical considerations
Visual Working Memory Task (based on Hannula, 2015)
Design and Procedure
EEG Data Acquisition and analysis
ERP Processing
Statistical Analysis

Results
Pilot Study Analysis
Demographics
ERPs
Visual Analysis of EEG 3D Amplitude Maps
Power Analysis
PSYSCAN Study Analysis
Demographics
ERPs
Independent samples t-test
Visual Analysis of EEG 3D Amplitude Maps

Discussion
P300 ERP components in a visual working memory task
Mesial sources contribution to scalp EEG
Hippocampus activation and Visual Working Memory
P300 ERP in UHR subjects
Hippocampal activity detection in UHR subjects
Strengths of the current study
Limitations of the current study
Future directions

Conclusion

References

Appendices

APPENDIX A: Demographic information for all samples from pilot study and PSYSCAN study

APPENDIX B: P300 ERP-Waveform Amplitude and Latencies for Each Participant at channels PZ and FZ

Acknowledgements

I appreciate all the help, love, and support from my dear Ibbi

I would also like to thank my supervisor, Judith Nottage, for all her help and effort throughout the year

Abstract

Background: Schizophrenia is described as an incapacitating, chronic and severe mental illness which affects about 1% of the population. Among the most frequently prominent of the cognitive symptoms in schizophrenia are deficits in working memory. More recently, individuals at ultra-high risk (UHR) of psychosis have been proposed to help provide awareness on the nature of prodromal stages and further acknowledge the initial stages to offer possibilities for early and more distinct interventions. It is particularly critical to perform studies on UHR of psychosis subjects as around 30% of UHR people experience progression into psychosis within two years.

Methods: A pilot study was conducted (8 females, 4 males) to examine visual P300 amplitude and detect hippocampal activity through scalp EEG, using the ICA analysis methodology. A smaller separate study was also conducted amongst UHR subjects (3 males, 1 female) and controls (2 males, 1 female).

Results: Findings revealed a pattern of high amplitude positivity across the ipsilateral anterior basal temporal, and mid parietal electrodes, alongside a low amplitude positivity distributed around the cheekbones; similar patterns were identified in UHR subjects. UHR subjects displayed a higher P300 amplitude compared to controls, contrary to previous findings.

Conclusion : The results of the present study provide a stepping stone for future studies to conduct further research incorporating additional source localisation analysis such as sLORETA. Understanding the location of the source of the P300 could allow prospective studies to determine and predict conversion to psychosis and act as possible biomarkers of psychosis amongst individuals with UHR, allowing a platform to provide early interventions for these at-risk individuals.

Table of Figures

Figure 1 shows the experimental paradigm and example of mismatched stimuli.Figure 1 shows the experimental paradigm and example of mismatched stimuli. 16

Figure 2 shows the grand average event-related potentials for mismatched target stimuli generated at channels PZ and FZ. 20

Figure 3 shows 3D amplitude scalp maps representing hippocampal activity, and the ERP-waveform for the components, for 3 samples of the pilot study. 22

Figure 4: Grand averages to the mismatched stimuli for controls and UHR participants. 25

Figure 5 shows 3D amplitude scalp maps representing hippocampal activity, and the ERP-waveform for the component, for UHR and a control participant. 27

Introduction

Schizophrenia is described as an incapacitating, chronic and severe mental illness (Ajinkya, Jadhav and Rajamani, 2015) which affects about 1% of the population (American Psychiatric Association, 2013). Schizophrenia is marked by positive, negative and cognitive symptoms that can result in severe impairment of social and occupational functioning (Andreason and Olsen, 1982). Cognitive symptoms vary amongst patients with schizophrenia but mainly include impaired working memory, attentional processing deficits and poor executive functioning (Bora, Yucel and Pantelis, 2010). These cognitive deficits can be socially incapacitating and are the least effectively treated symptoms (Gibbons and Dean, 2016). Despite cognitive dysfunction being an established characteristic of schizophrenia, controversy lies around the development and trajectory of these cognitive deficits. The main debate concerning the course of cognitive deficits is whether schizophrenia is a consequence of neurodevelopmental or neurodegenerative progress. Neurodevelopmental theories propose that cognitive deficits exhibited amongst schizophrenia patients are the consequence of atypical development of the brain resulting in problems in cognition. Conversely, evidence from numerous studies has denoted that such cognitive and intellectual shortfalls are apparent initially in neurodevelopment considerably prior to the onset of psychosis (Reichenberg, Caspi and Harrington et al., 2010; Maccabe, 2008; Woodberry, Guiliano and Seidman, 2008). Most evidence establishing cognitive decline in schizophrenia is constructed on indirect evaluation of cross-sectional studies looking at schizophrenia patients through distinct stages of the disorder (chronic, first episode, ultra-high risk [UHR] to psychosis) compared to healthy controls. The current evidence suggests that cognitive deficits in UHR psychosis are considerably reduced in severity in contrast to first-episode psychosis (Guiliano et al., 2012; Fusar-Poli et al., 2012), implying possible cognitive deterioration over the shift in psychosis, which may be consequential to the neurobiological alterations that indicate the development of psychotic symptoms. One meta-analysis compared cognitive data from 23 studies incorporating 1106 patients and 1385 controls published from 1992 to 2013. The findings of this meta-analysis established that there was significantly worse performance amongst schizophrenia patients compared to healthy controls throughout entire cognitive domains, incorporating working memory, speed of processing, attention and visual memory (Fatouros-Bergman, Cervenka, Flyckt, Edman & Farde, 2014).

Schizophrenia and Visual Working Memory

Among the most frequently prominent of the cognitive symptoms in schizophrenia are deficits in working memory (WM) (Heaton et al., 1994; Fiorovanti et al., 2005; Fioravanti, Bianchi & Cinti, 2012). WM is a multifaceted construct encompassing component processes that facilitate the short-term maintenance of information to guide goal-orientated behaviour. WM supports a range of cognitive abilities involving learning, reasoning, and academic success. To understand the specific characteristics of WM that may be compromised in schizophrenia, it is beneficial to discuss existing models of WM role, such as Baddeley’s model (Baddeley, 2000). Baddeley’s model insinuates four major components of WM: 1) the visuo-spatial sketch pad, a temporary storage buffer for visual information; 2) the phonological loop, a short-term storage buffer for verbal information; 3) the central executive, which maintains the manipulation and amendment of information interned within the storage buffers; and 4) an episodic buffer, in which intricate, multi-modal occurrences are assimilated and stored on-line (Baddeley, 2000). Due to WM’s significance in cognition, it is not unanticipated that WM deficits in schizophrenia are linked with diminishments in social and occupational functioning (Reichenberg, 2014). Thus, recognising interruptions in the component processes in WM in schizophrenia is essential to understanding not only cognitive function in the disorder but likewise the disorder itself. In particular, visual working memory (VWM) is of great interest as it has found to be strongly associated with overall cognitive ability (Luck & Vogel, 2013). According to Baddeley’s model, the visuo-spatial sketchpad and central executive buffer are the most fundamental components for VWM.

Several studies have shown that schizophrenia patients exhibit impaired VWM (Fuller et al., 2009; Hahn et al., 2010; Kruguljac, Srivastava & Lahti, 2013). VWM can be outlined as ‘the active continuation of visual information to employ the requirements of ongoing tasks’. Stoimenova-Popova et al. (2017) investigated the association between VWM and schizophrenia by examining 89 patients with paranoid schizophrenia using the Benton visual retention test (BVRT). The study’s findings recognised that dysfunction in VWM was common amongst patients with paranoid schizophrenia. Additionally, the results indicated that female sex and high education was correlated with improved test performances. Another study conducted by Hui et al. (2016) assessed the alterations in cognitive function preceding relapse by observing visual memory and verbal working memory in a one-year prospective randomised controlled trial of remitted first-episode psychosis patients allocated to either maintenance of medication (quetiapine 400mg/day) or medication withdrawal (placebo). Participants were evaluated monthly for relapse (reoccurrence of positive symptoms of psychosis), visual memory using the Visual Patterns Test and verbal working memory through the Letter-Number Span Test. Results showed that relapse was correlated with VWM worsening 2 months before relapse (odds ratio (OR) 3.07, 95% confidence interval (CI) 1.19– 7.92, P = 0.02). This may suggest initial brain dysfunction that indicates a psychotic relapse. A meta-analysis was conducted to investigate whether significant cognitive deficits are also present in schizophrenia patients in the absence of medication, which has also been shown to play a role in cognitive declination. Cognitive data was obtained from 23 studies involving 1106 patients and 1385 controls, and included studies published from 1992 to 2013. The overall results from the meta-analysis showed that non-medicated schizophrenia patient’s performance was considerably inferior when compared to healthy controls, in all cognitive areas, with medium to large effect sizes. Additionally, findings showed that working memory, speed of processing and verbal memory were three main areas that exhibited the highest impairment (Fatouros-Bergman, Cervenka, Flyckt, Edman and Farde, 2014). This indicates the presence of substantial cognitive impairments in the early phase of schizophrenia without antipsychotic medication, suggesting the possibility of detecting biomarkers for the illness through further research in the early stages of schizophrenia. Since the primary stages are less influenced by medication, substance abuse and/or aging, research into this population group may generate indications for prevention and successful management of schizophrenia (Insel, 2010).

Ultra-High-Risk of psychosis

Recently, individuals at ultra-high risk (UHR) of psychosis have been proposed to help provide awareness on the nature of prodromal stages and further acknowledge the initial stages to offer possibilities for early and more distinct interventions. Individuals who exhibit three of the following risk syndromes: attenuated positive symptoms, brief limited intermittent psychotic symptoms (BLIPS), and vulnerability to psychosis, are outlined as being at UHR of psychosis (Yung et al., 2007). It is particularly critical to perform studies on UHR of psychosis subjects as around 30% of UHR people experience progression into psychosis within two years (Cannon et al., 2008; Morrison et al., 2012). The effects of confounding variables such as medication can be circumvented by considering cognitive function in treatment-naive subjects who have a UHR of developing psychosis (Fusar-Poli et al., 2013). Also, UHR individuals who do not proceed to psychosis could be susceptible to additional mental illnesses (Roessler et al., 2011), and have displayed maintenance of inferior functioning, compared to healthy controls, with continual disability at least at 2.5 years after a diagnosis of psychosis risk syndrome (Addington et al., 2011).

Evidence has indicated that cognitive impairments are a common issue in UHRP patients and is a central feature of the pre-clinical illness (Rhinewine et al., 2005; Meshola –Gately et al., 2009; Hofer et al., 2011). However, despite numerous research conducted in this population, the findings have been conflicting, with particular studies who testified significant variations, whilst others discovered no significant disparities (Fusar-Poli et al., 2010) to matched controls, and the outline of the neurocognitive deficiencies recognised have been inconsistent across studies.

Ultra-High-Risk of psychosis and Visual Working Memory

More specifically, behavioural deficits in WM processing have discovered to be apparent before the commencement of schizophrenia in UHR psychosis (Fusar-Poli et al., 2012). One study aimed to investigate whether the MATRICS (Measurement and Treatment Research to Improve Cognition in Schizophrenia) battery will distinguish between subjects at UHR psychosis and a control group in regards to affected areas, by measuring neuropsychological functioning in 27 UHRP patients and 38 healthy controls. Findings showed that UHR participants scored 0.5 to 1.7 standard deviations below controls in WM, verbal and visual learning, and social cognition (Serrani, 2011). Further, a meta-analytical review revealed overall impairment in high-risk subjects compared with controls in all neurocognitive domains. Vulnerability to psychosis was correlated with neurocognitive deficits in executive function, verbal fluency, attention, visual and verbal memory, and working memory (Fusar-Poli et al., 2012). Similarly, other meta-analyses investigating cognitive deficits in UHR subjects in contrast to healthy controls uncovered evidence of cognitive diminishment in UHR adolescents and youth (Guiliano et al., 2012; Bora, Lin, Wood, Yung, McGorry & Pantelis, 2014). Neurocognitive functioning was examined in individuals at UHR of psychosis, first-episode schizophrenia and healthy controls through an ample neurocognitive battery which comprised of assessments for five specific neurocognitive domains (executive function, attention/working memory, processing speed, verbal memory and spatial memory). Participants were examined for transition every month for 24 months of follow-up. The researchers found that attention/working memory and verbal memory in the UHR group considerably differed from the first-episode schizophrenia and healthy control groups (Bang et al., 2014). These findings help to validate the neurodevelopmental model of schizophrenia and propose that there may be distinctive progressive courses between converters and non-converters to psychosis.

Herdt et al. (2013) aimed to characterise differences in neurocognitive functioning between psychosis-converters and non-converters. The researchers carried out a meta-analysis of 9 studies comprising 583 clinically high risk subjects. Results indicated that clinical high risk subjects that converted to psychosis performed significantly worse on 2 MATRICS domains, namely working memory and visual memory, in comparison to the clinical high risk group that did not convert. These results are of huge significance for preventive interventions in psychosis. Cognitive deficits in UHR subjects may justify for the exhibiting symptoms and difficulties, which are frequently more of an alarm to individuals than their long-standing risk of shift to psychosis (Fusar-Poli et al., 2009). Cognitive dysfunction has been found to be related to a variety of fundamental consequences in psychotic disorders including relapse rates, time spent in the hospital, levels of symptoms, social functioning, vocational functioning, and independent living/residential status (Allott, Proffitt & Killackey, 2011). It is, therefore, vital that biomarkers can be identified using visual working memory tasks to obtain a more established understanding of the illness to help improve outcomes for these patients.

Hippocampus and Visual Working Memory

Traditionally, the hippocampus was considered as a brain region associate with declarative long-term memory. Conversely, an accumulative volume of evidence points beyond the long-term memory hypothesis, demonstrating that the hippocampus is activated during the administration of relational memory (Eichenbaum,2004) or spatial and spatiotemporal discontiguity (Staresina and Davachi, 2009). It has also been continually discovered that the hippocampus is activated during WM maintenance of novel items (Axmacher etal.,2010; Fuentemilla et al., 2010; Poch et al., 2011). Intracranial EEG recordings in the hippocampus of epilepsy patients exhibited that continuation of accumulative WM load was correlated with higher negativity of evoked response potentials (Axmacher et al., 2007), and elevations in theta/gamma phase amplitude coupling (Axhmacher et al., 2010). One study evaluated visual short-term memory in patients with impairment to the medial temporal lobe (MTL) and controls, for high resolution and low resolution object-location and object-colour associations. The patients demonstrated significantly compromised visual short term memory; this was shown to be higher for the high-resolution object-location and object-colour bindings (Koen, Borders, Petzold & Yonelinas, 2016). Together, the evidence suggests that the hippocampus plays a role in VWM.

Hippocampal Impairments in Schizophrenia

There have been many suggestions that the hippocampus as being central to the neuropathology of schizophrenia. The evidence arises from a range of approaches, both in vivo (through structural and functional imaging) and post-mortem studies. One study conducted by Ragland et al. (2017) used functional magnetic resonance imaging (fMRI) to analyse the assumption that activity in posterior hippocampus is excessively reduced in schizophrenia, predominantly through spatial memory retrieval. During encoding, participants were familiarised to essential items through questions about item features or spatial location. The participants were required to indicate whether scenes were changed or unchanged. Results indicated that patients with schizophrenia displayed reduced stimulation in the posterior hippocampus during recognition of spatial changes but not during recognition of item changes. Patients also presented with amplified activation of anterior hippocampus during detection of item changes. Another fMRI study also found similar results (Wilkins et al., 2017). The researchers tested the hypothesis that individuals with schizophrenia spectrum disorders (SSD) have discriminating impairment, through the use of a hippocampal dependent spatial navigation strategy in SSD, schizophrenia, schizoaffective and control participants. Findings indicated that the participants with schizophrenia and schizoaffective disorder who implemented a spatial strategy exhibited inferior performance, and had less hippocampal activation in comparison to healthy controls who used either strategy, and SSD participants who used a response strategy. These results encourage the supplementary progress of protocols to train compromised hippocampal-dependent abilities.

The P300 event related potential

Electrophysiology, a non-invasive imaging technique characterised by superior temporal resolution is ideal for exploring cognitive processes and psychopathology in vivo. Event related potentials (ERPs) are variations in the electroencephalogram (EEG) that are usually examined after a particular stimulus or cognitive task is presented (Woodman, 2010). The P300 event-related potential (ERP) is a positive deflection of the EEG with a peak at ~300 to 500 milliseconds, and is associated with attention and memory processes (Nehra, Grover, Chetri, Sood & Das, 2012). The P300 is obtained by intermittent task-relevant stimuli entrenched in a sequence of recurring presentations of a typical stimulus (Polich, 1998; Duncan et al., 2009). The P300 is one of the most exemplified physiological biomarkers in neuropsychiatric research. The P300 amplitude is extensively understood as a physiological correlate of cognitive resources apportioned to processing the task-relevant stimulus; more simply, a measure of cortical activation through attentional efforts (Polich, 2007; Azizian and Polich, 2007) It is essentially an EEG correlate of continuous attended and working memory processes (Polich, 2007). The P300 latency is typically construed as a fundamental correlate of reaction time and is believed to indicate the rate of neural transmission (Polich, 2007; Telles, Singh & Puthige, 2013). There are two major sub-components of P300 that have been well investigated. The P3a subtype is constructed in the absence of a task, when an irregular distractor in a sequence of recurrent stimuli is presented. It is associated with automatic attention processing and is more distributed around the frontal regions. The p3b subtype is stimulated by irregular and task-relevant target stimuli through an oddball paradigm. The P3b is mostly distributed in parietal regions and is understood to reflect the load of attentional resources apportioned to the recognition of target stimuli (Azizian & Polich, 2007; Onitsuka et al., 2013). The P300 signal is produced from the summation of activity from numerous brain locations, specifically the diverse association regions of the cerebral cortex and the limbic system (Polich, 2007; Mangalathu-Arumana et al., 2012). Intracranial recordings have exhibited that the P300 is a component with a manifold of generators comprising the prefrontal, anterior cingulate, superior temporal and parietal cortices as well as the hippocampus (Onitsuka et al., 2013). Further, it has been suggested that the neurophysiological generators of P3a, in particular, coincide within the prefrontal cortex, hippocampus and striatum (Alho et al., 1994; Escera and Corral, 2007). However, despite a substantial quantity of research, not many studies have successfully been able to detect hippocampal activity through the P300 component using scalp EEG.

P300 Impairments in Schizophrenia

A wide range of evidence from research studies has indicated that patients with schizophrenia have reduced P300 amplitudes and latency prolongations in comparison to healthy controls (Ozgurdal et al., 2008; Shin et al., 2010; Nagai et al., 2013). An ERP study conducted by Oribe et al. (2015) established that first-episode psychosis patients exhibited an impairment in the visual P300 ERP component in comparison to healthy controls. Further, the researchers found that the trajectory of schizophrenia had an influence on the cognitive function of visual working memory. Supportive evidence has also been provided through two meta-analyses of P300, correspondingly in schizophrenia patients (Bramon et al., 2004) and in patients’ relatives (Bramon et al., 2005). The findings showed decreased P300 amplitude and prolonged latency amongst both the schizophrenia patients and their relatives; these results are in line with evidence from other research findings. However, there are many factors that may have influenced the P300 latency effect size, such as disease duration (Jeon & Polich, 2003). Delayed P300 latency exhibited among chronic schizophrenia patients may not be consistent in first-episode schizophrenia patients. To this date, there have been inconsistent results on P300 latency variations amongst first-episode schizophrenia patients; some research studies report considerably delayed P300 latency in patients (Demiralp et al., 2002; Chen et al., 2010; Lee et al., 2010), whereas others have reported varying results (Brown et al., 2002; Devrim-Ucok, Keskin-Ergen & Ucok, 2006; Kayser, Tenke, Gil & Bruder, 2010).

The P300 as a putative biomarker of psychosis risk

More recently, there has been a growing interest in the possibility of ERP components being used as a potential biomarker of psychosis amongst UHR individuals. ERP studies of UHR individuals and first-episode schizophrenia allow researchers to evaluate neurocognitive function integrity, comprising early sensory and later working memory processes. ERPs reveal distinctive sensory and cognitive processes, and may propose neurocognitive indicators of brain function during the clinical high risk state. Specifically, the P300 is of interest due to previous evidence suggesting P300 impairment in schizophrenia.

Recent studies on prodromal subjects have established auditory P300 abnormalities (Ozgurdal et al., 2008). One study investigated whether P300 would be a prospective biomarker for schizophrenia patients (Wei et al.,2016). The researchers used the auditory oddball paradigm as a form as assessment in 36 individuals at UHR for psychosis and 35 healthy controls, whilst recording auditory P300. The P300 was measured as the largest positive voltage in the 280-450 milliseconds time window. Findings indicated that the UHR individuals had decreased P300 peak amplitudes at FZ, CZ, and PZ. Additionally, the P300 peak latency at PZ was larger in the UHR group compared to the control group. A positive correlation (r= .54) was established between P300 peak latency at CZ and positive symptom scores on the Scale of Prodromal Symptoms. A positive correlation between P300 peak amplitude and information processing speed was also observed (r= .34). Another study investigated visual P300 in prodromal subjects (n= 23), first-episode schizophrenia (n=17) patients and healthy controls (n= 31), through a novelty experimental paradigm where participants were required to silently count the infrequent target stimuli embedded within standard stimuli, presented on a screen. Findings showed that both the prodromal and first-episode schizophrenia groups exhibited reduced P300 amplitudes and delayed P300 peak latencies compared to healthy controls. These results indicate that visual P300 is already previously altered at the prodromal stage and may show prospective potential to be an indicator of the prodromal phase of schizophrenia (Oribe et al., 2013). However, visual P300 findings in schizophrenia patients are inconsistent, and details on visual P300 in prodromal subjects are very limited (Lee et al., 2010). It is important that research is conducted using UHR individuals as studies have shown that approximately 30% of UHR subjects develop psychosis within two years (Cannon et al., 2008; Morrison et a., 2012). Identifying visual P300 abnormalities through visual working memory tasks in UHR individuals compared to healthy controls would allow for the detection of any possible biomarkers for psychosis.

Detecting hippocampal activity through scalp EEG

As mentioned earlier, the development of schizophrenia is believed to influence the cognitive function of VWM (Oribe et al., 2015). Further findings show that UHR individuals have also exhibited impaired WM (Serrani, 2011; Bang et al., 2014), which has been shown to be associated with hippocampal dysfunction (Lett, 2014). Therefore, it is important to understand the relationship between VWM functioning and the hippocampal activity to help detect biomarkers for cognitive dysfunction in psychosis, which is of huge significance for psychiatric research. Mesial temporal sources are considered to escape identification in scalp EEG recordings based on the deep localisation and enclosed geometry of mesial temporal structures. One study attempted to analyse simultaneous scalp and intracerebral EEG recordings to allocate the involvement of mesial temporal sources to scalp EEG. The findings of this study showed that hippocampal activity can be detected maximally in the vicinity of the cheekbone (Koessler et al., 2015). More specifically, the researchers found that scalp EEG correlates of mesial temporal sources were measureable with a negativity in the ipsilateral anterior basal temporal electrodes. Additionally, another study investigated the role of the hippocampus in both novelty detection and in long-term memory (Emmanuel et al., 2017). The researchers recorded intracerebral evoked potentials from the inside of the hippocampus of epileptic patients, during memory and novelty detection tasks. The results indicated that memory and detection tasks evoked late local field potentials in the hippocampus during the same episode. The novelty detection tasks elicited negative polarity, whereas the memory tasks elicited positive polarity at around 260-600 milliseconds post-stimulus. It must be noted that very limited research has been conducted investigating the link between hippocampal activity and VWM amongst UHR of psychosis individuals, and therefore the link between these two remains unclear.

Rationale, Aims and Hypotheses

The first part of the current research study conducted was a pilot study investigating the link between the visual P300 ERP component and VWM tasks amongst healthy participants. The study aimed to detect the peak P300 amplitudes and latency, as well as electrodes through which the P300 could be identified. Thereafter, the pilot study aimed to detect hippocampal activity through electrodes placed on the vicinity of the cheekbones. The study was concerned with investigating which electrodes hippocampal activity could be detected through, and the time-point at which this was identified. Finally, the pilot study was interested in exploring whether the visual P300 ERP corresponded to the activation of the hippocampus.

The second part of the study aimed to examine the link between visual P300 ERP performance and VWM tasks amongst UHR subjects and healthy controls. The study also aimed to detect and compare hippocampal activity from the identified electrodes during the pilot study.

It was hypothesised that the both the P3a and P3b ERP would be detected using the VWM task, with no differences in amplitude and latency between the two ERPs. Secondly, it was hypothesised that UHR subjects would have reduced visual P300 amplitudes as well as delayed latencies in comparison to the healthy control group. Thirdly, it was hypothesised that we will be able to detect hippocampal activity from the cheekbone electrodes in both the pilot and UHR sample.

Methods

Participants

Pilot study sample

The current pilot study recruited a total of fifteen participants (age: 23-42 years, nine females; Table 1 for details) using opportunity sampling through word of mouth and research advertisements. This study was approved by the Research Ethics Committee.

PSYSCAN study sample

A total of eight participants were recruited in the study (Ultra-High Risk of psychosis, n= 4; healthy controls, n=4); Appendix A). Ultra-High Risk (UHR) participants were recruited through PSYSCAN, from the OASIS service for people at risk of psychosis. The UHR group met the Personal Assessment and Crisis Evaluation (PACE) criteria on one or more of the following groups: i) attenuated psychotic symptoms (unusual beliefs or magical thinking, abnormal perceptual experiences, excursive speech, odd behaviour/ appearance), ii) brief intermittent psychotic symptoms (full-blown psychotic symptoms which persist for less than one week and settle unexpectedly) or iii) vulnerability to psychosis (either have a relative with a psychotic illness and/or have schizotypal personality disorder, plus a distinct diminution in Global Assessment of Function score) (Yung et al., 2007). Further, UHR for psychosis subjects were included in the study if their assessment using the Schizophrenia Proneness Instrument (Schultze-Lutter et al., 2006) fulfilled the basic symptoms criteria.

Inclusion and exclusion criteria

The participants must have been able to speak English at a level whereby they had the ability to provide informed consent, and efficiently follow instructions for the EEG paradigm. The participants were screened to ensure that none of the healthy participants had any personal or family record of a psychiatric condition. The participants did not use any psychotropic, antidepressant or antipsychotic medication that may have an influence on results. Those that were using such medication were not included in the study. Participants were asked to specify their caffeine and cigarette intake before the experimental procedure, with the quantity noted, as these have been acknowledged to affect EEG measurements. Potential participants that met the DSM-IV criteria for abuse or dependency on drugs and/or alcohol were excluded. Exclusion criteria also included any participants with records of neurological or key medical illness or head injury. Likewise, subjects that may have experienced reactions to cosmetics were not included in the study to prevent any possible risk of reaction from the EEG conducting gel. All 15 participants from the pilot study sample and all 8 UHR and control participants from the PSYSCAN study successfully fulfilled the mentioned inclusion criteria.

Ethical considerations

The current study was conducted per the principles of the Declaration of Helsinki (Amendment, 2008), in addition to all appropriate regulatory requirements. Before consent, participants were assessed to ensure they had capacity to provide informed consent, and understand instructions for the task. The study was explained to each eligible participant both verbally and in written form on the consent form. Participants were made aware at the time of consent that they could withdraw from the study at any point in time, with or without a reason provided. They were also able to request for their data to be removed from additional analysis, should they want to, if this was requested within a provided time-frame. If the participant consented to take part in the study, and was later followed by the decision of premature withdrawal before the completion of the assessment, the gathered data up to that time-point was not discarded unless exclusively requested for by the participant. All data was anonymised, and was stored electronically, without any information that could potentially be used to identify a participant, under password protection. The paper copies of identifying information were stored independently in a locked filing cabinet.

Visual Working Memory Task (based on Hannula, 2015)

The visual working memory task consisted of 85 stimuli. The stimuli included both matched pairs and mismatched pairs of various scenes It was emphasized that the pictures would be nearly identical, but that one was an exact match of a scene presented earlier, and that the other was a manipulated version of that scene. This task is considered to index visual working memory. The background was white throughout the entire task ( Figure 1).

Figure 1 shows the experimental paradigm and example of mismatched stimuli.Figure 1 shows the experimental paradigm and example of mismatched stimuli.

A) B)

Abbildung in dieser Leseprobe nicht enthalten

Experimental paradigm. A) Timeline of a trial. The boxed texts present the components of the experimental session. Time was measured in milliseconds (ms). The directional arrow shows the order of each trial. B) Example photographic mismatched stimuli as shown in each of the two conditions. All photographs were presented on a white screen.

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Details

Pages
49
Year
2017
ISBN (eBook)
9783668700802
ISBN (Book)
9783668700819
File size
914 KB
Language
English
Catalog Number
v418222
Institution / College
King`s College London
Grade
Merit
Tags
propagation independent component analysis

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Title: Propagation of hippocampal activity in ultra-high risk schizophrenia psychosis subjects using Independent Component Analysis