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Predicting hydromorphological responses to dam removal
Full text linkEng D ThesisThe alteration of flow regimes through abstraction and impoundment represents a major threat
to aquatic species and ecosystems. Dam and weir removal have become attractive restoration
measures for mitigating flow regime alteration, habitat fragmentation and other ecological
impacts. Yet, large heterogeneity between study sites, a lack of historical data and complex
underlying processes, mean predicting the hydromorphological response remains challenging.
In this work, the novel application of Physically Based Spatially Distributed catchment
modelling, Geomorphic Modelling and Level Pool Routing combined with extensive
fieldwork is used to predict the hydromorphological consequences of weir removal at
Ennerdale Water; a Special Area of Conservation in the Upper Ehen catchment, where
impoundment and abstraction date back to the 1800s. The area is home to the last remaining
stronghold of endangered freshwater pearl mussels in England and Wales and is subject to
unique natural and managed conditions.
Using historic flow regime data, a national-scale assessment of freshwater pearl mussel rivers
is conducted. It shows that healthier mussel populations inhabit rivers with less extreme
fluctuations between low and high flows and catchments with lower magnitude high flow
events. Healthy populations, however, are found in both regulated and unregulated rivers.
Abstraction has reduced mean flows in the Upper Ehen by 10% from 1995-2019. Without
impounding infrastructure and flow regulation, minimum flows are predicted to fall by around
65% with no change to Q95 values. In the event of weir removal, mean lake levels are
predicted to fall by 0.95m, resulting in a 5% reduction in the surface area of Ennerdale Water.
The novel application of water-borne ground penetrating radar has shown evidence of historic
lake outlets and previous lateral channel movement at the head of Ennerdale Water. Lakebed
analysis identified small pockets of fine sediment, totalling an estimated 825 m3
, directly
upstream of the weir. Chemical analysis identified no high levels of contamination. Following
weir removal, sediment transport rates were predicted to vary between 0.25 m3 and 309m3 per
year, averaging around 30 m3
/year. Transport was highly correlated with extreme high flows.
Correctly managed weir removal represents an opportunity for United Utilities to align the
interests of regulators, customers and wider stakeholders. The hydrological and geomorphic
results presented, provide critical and unique evidence for achieving this outcome.
Furthermore, this study presents a novel and thorough methodology for investigating weir and
dam removal that can be applied to other sites requiring ecological restoration
Targeting Kinases with Small Molecule Covalent Inhibitors
Full text linkPhD ThesisProtein kinases are considered the largest and most functionally diverseenzymesuperfamily critically involved in the regulation of almost all cellular process. Theyareone of the most intensively pursued targets, particularly in cancer drugdiscoveryprograms. In the case of cancer therapy, covalent inhibitors have proven to be
better than reversible inhibitors and several kinases targeted covalent inhibitors are in clinical use. In this thesis, irreversible inhibition of NF-κB inducing kinase(NIK) and Epidermal growth factor receptor (EGFR) is investigated. NIK is an essential upstream kinase, which regulates activation of the noncanonical
NF-κB pathway involved in lymphoid organ development and adaptive immune responses. Numerous genetic studies demonstrated that the aberrant expression or regulation of NIK is associated with several disease states including cancers. The NIK kinase has been targeted for drug therapy by small molecule reversible
inhibitors,but many of them were impractical for in-vivo administration due to poor selectivity or pharmacokinetic properties. Achieving potency and selectivity in NIK inhibitors is particularly challenging due to its constitutive activity, high ATP affinity (Km4µM) and relatively shallow binding pocket. Developing an irreversible inhibitor of NIK that targets active site Cys-444, which is unique to NIK, is expected to deliver greatly improved selectivity and superior efficacy. Extensive structure-activity relationshipstudies (SARs) based on literature NIK inhibitors have led to lead benzimidazole28.
Benzimidazole 28 exhibits NIK potency of 0.18 µM and has been confirmed to bind covalently to NIK Cys-444, but has poor selectivity profile inhibiting both NIK dependent and independent cell lines. Co-crystallisation studies using28werecarried out to understand the binding mode in NIK and identify structural features to exploit to achieve better potency and selectivity in future analogues.
SAR studies around the hinge binding motif, benzimidazole core structure, and covalent warhead were investigated, and a number of analogues were designed and synthesised. A scaffold hopping approach based on recently published NIK inhibitors was also carried out with the aim of improving the compound potency and selectivity. EGFR is critically involved in cell signalling pathways that control cell growth, proliferation, and survival. Multiple generations of EGFR TKIs have been approved for clinical use. Mutations or over-expression of EGFR have been discovered in association with many types of cancers providing a rationale for efforts to
inhibit
EGFR. Multiple generation of EGFR TKIs have been developed and approved for
clinical use. Despite the documented efficacy of FDA approved third generation EGFR TKIs, new EGFR mutations and other drug resistance mechanisms emerge rapidly after treatment leaving patient without further therapeutic options other than chemotherapy and local ablative therapy. Multiple mechanisms of resistance were detected in clinical trials with tertiary C797S mutation accounting for more than20%incidence rate and the most difficult to deal with. It was proposed that developing an irreversible inhibitor of EGFR by targeting Cys-775 would deliver a new therapeutic option for patient who develop resistance to third generation EGFR TKIs. Extensive structure-activity relationship studies were conducted based on literature compounds have led to lead pyrimidopyridone 128.
Pyrimidopyridone 128 exhibits a potency of 107 nM in the TMTR-FRET assay and has been confirmed to be a covalent inhibitor of EGFR targeting Cys-775. Co-crystallisation studies using 128 were carried out to understand the binding mode in EGFR, and to help in identifying structural features to exploit to achieve better potency.
Further SARs studies to improve the compound potency were conducted in which SARs around the phenyl ring were undertaken. Compounds with electron rich phenyl
ring were more potent than compounds with electron deficient phenyl ring. AQSAR study revealed that compounds with electron donating substituents were more potent regardless of the position of the substituents, but no obvious relationship was observed with the lipophilicity. The outlier of this was compound 151, which was the most potent compound in this series, though not the one with the most electron rich phenyl ring suggesting that the sulphonamide group at the para-position was making an additional interaction within the sugar pocket. Modelling of compound151withdouble mutant EGFR revealed the proximity of several functional groups that may act
as H-bonding partners to the sulphonamide moiety in compound 151 (Ser-797intriple mutant EGFR, Asn-842 and Ser-720).
TJordan University of Science and Technolog
Data-driven modelling and monitoring of industrial processes with applications in nuclear waste vitrification
Full text linkPhD ThesisProcess models are critical for process monitoring, control, and optimisation. With the
increasing amount of process data and advancements in computational hardware, data-driven
models are a good alternative to mechanistic models, which often have inaccuracies or are too
costly to develop. One problem with data-driven models is the difficulty in ensuring that the
models perform well on new data and produce accurate predictions in complex situations, which
are frequently encountered in the process industry.
Within this context, part of this thesis explores developing better data-driven models through
using a latent variable technique, known as slow feature analysis, as a pre-processing step to
regression. Slow feature analysis extracts slow varying features that contain underlying trends
in the data, which can improve model performance through providing more meaningful
information to regression, reducing noise, and reducing dimensionality. Firstly, the
effectiveness of combining linear slow feature analysis with a neural network is demonstrated
on two industrial case studies of soft sensor development and is compared with conventional
techniques, such as neural networks and integration of principal component analysis with a
neural network. It is shown that integration of slow feature analysis with neural networks can
significantly improve model performance. However, linear slow feature analysis can fail to
extract the driving forces behind data in nonlinear situations such as batch processes. Therefore,
using kernel slow feature analysis with a neural network is proposed to further enhance process
model performance. A numerical example was used to demonstrate the effective extraction of
driving forces in a nonlinear case where linear slow feature analysis cannot. Model
generalisation performance was improved using the proposed method on both this numerical
example, and an industrial penicillin process case study.
Dealing with radioactive nuclear waste is an important obstacle in nuclear energy. Sellafield
Ltd have a nuclear waste vitrification plant which converts high-level nuclear waste into a more
stable, lower volume glass form, which is more appropriate for long term storage in sealed
containers. This thesis presents three applications of data-driven modelling to this nuclear waste
vitrification process. A predictive model of the pour rate of processed nuclear waste into
containers, an early detection system for blockages in the dust scrubber, and a model of the
long-term chemical durability of the stored glass waste. These applications use the previously
developed slow feature analysis methods, as well as other data-driven techniques such as
extreme learning machine and bootstrap aggregation, for enhancing the model performance.Engineering and Physical Sciences Research Council (EPSRC) and
Sellafield Lt
The entrepreneur-financier relationship across institutional logics: A study in Thailand
Full text linkPh. D. Thesis.Entrepreneurs can draw support from various types of financiers, including crowdfunding,
angel investors, venture capital funds, corporate venture capital funds, and public subsidies.
However, most research focuses on a single source of finance, most often venture capital funds. Prior
studies do not give a complete picture of how the relationship between entrepreneurs and investors
unfolds over time. The focus is mainly on how investment decisions aremade, even though engagements
after striking a deal are equally crucial to the relationship. These gaps in understanding offer an
opportunity to understand entrepreneurs and their contexts, particularly when looking at the microlevel entrepreneur-financier dyad. In addition, as Welter (2011) notes, contexts matter. These
contexts have a multiplicity of levels in that they both intertwine with and shape regulatory and
normative contexts at wider levels (community, regional, and national). The entrepreneurfinancier dyadic relationship is arguably formed in a broader context. It is thus worth
considering the potential effect of context on the relationship.
This research explores the relationships between entrepreneurs and financiers in Thailand using
an institutional logics perspective: a value system that prescribes behavioural templates for
focal actors (Thornton et al. 2012). The focus is on the context of how a relationship is fostered
during a new venture financing process. By examining fine-grain differences in practices
between entrepreneurs and various financiers, the research deconstructs what comprises the
emergence of their relationships and explains the distinct context within which each pathway is
formed. This is a promising lens for explaining differences in entrepreneur-financier
relationships. The literature has conceptually suggested that each type of financiers will possess
dominant institutional logics, and such logics will shape their interactions with entrepreneurs
when assessing prospective deals. The study utilises a qualitative research design involving indepth interviews with entrepreneurs and financiers – corporate venture capitalists, venture
capitalists, angel investors, and government funding agencies – in Thailand. A total of 36
interviews were conducted with 20 entrepreneurs and 16 financiers.
This thesis proposes a comprehensive framework that delineates the emerging relationships
between entrepreneurs and various types of financiers. Each path develops under its own
practices with hybrid logics that are underpinned by the broader context. However, the
institutional logics shaping the relationship deviate from those previously characterised in the
3
literature. The most striking findings involve entrepreneurs’ relationships with corporate
venture capital and angel investors. The former are shaped by both corporate and professional
logics, whereas quasi-community logics shape the latter. A different relationship pattern is
found in government funding, shaped by state logic complemented by market logic. Practices
with venture capitalists coincide with those in the literature, indicating a predominance of
professional logics in the relationship. Based on these findings, practical recommendations are
provided for entrepreneurs planning to approach financiers in relation to what financiers look
for at different phases of relationship formation and what entrepreneurs can expect from
financiers. Policy recommendations are also offered for those interested in championing
entrepreneurship through the design of financing tools concerning institutional logics found in
entrepreneur-financier dyads in emerging economies
What lies beneath : investigating the distribution and dynamics of landslides in lakes, and fjords of New Zealand
Full text linkPhD ThesisSubaerial and subaqueous landslides are a significant hazard in intramountainous lake and fjord
landscapes across the globe. Landslides into, and within, the lakes and fjords can generate
tsunamis that present a risk to shoreline communities and infrastructure. Understanding the
landslide and associated hazard cascade (e.g. landslide tsunamis) is reliant on both identification
of deposits to assess their magnitude-frequency relationship, and detailed analysis of the
deposits, which can provide information on the landslide’s emplacement dynamics. This thesis
aims to better understand the distribution and dynamics of landslides within lakes and fjords in
the seismically active, high-mountain landscape of the South Island, New Zealand, to improve
the understanding of the hazard. Despite the similar physiographic setting to many global
counterparts (e.g. Norway, European Alps, western Canada, Patagonia), there have only been
a few studies to quantify the hazard from landslides into and within lakes and fjords of New
Zealand, compared to the subaerial landslide hazard. Previous research suggests that the lakes
and fjords of New Zealand may provide a well-preserved archive of previously unknown
landslide deposits.
A new literature-based inventory of lakes and fjords with known landslides is presented within
this thesis. In total, 15 lakes and 5 fjords were identified as having documented landslide events.
The lakes and fjords contain a variety of landslide types; including subaerial originating (n=7),
deltaic landslides (n=4), and mass-transport deposits, assumed to have originated from the
subaqueous slopes (n=7). Previous bathymetric data investigations in Lake Tekapo and Milford
Sound/Piopiotahi reveal deposits from multiple sources. Earthquakes are the main trigger, with
9 cases related to known earthquakes. Earthquakes are assumed to be the trigger in 5 further
lakes and fjords. In Milford Sound/Piopiotahi, morphological and morphometric analysis, and
numerical modelling by DAN3D of previously identified deposits from high-resolution
bathymetric data indicate that the landslides exhibit a variety of morphologies, morphometries,
and generally low apparent mobility. Factors such as transitioning from air to water, abrupt
slope angle changes from the steep fjord walls to flat basin wall, and lack of lateral confinement
resulting in freely spreading deposits appear to contribute to the apparent low mobility.
Furthermore, the best fit numerical simulations required high basal friction angles, and/or low
turbulence parameters to retard the landslide runout The modelling results also found a Voellmy
rheology to be effective in simulating the subaqueous portion of landslide runout, as varying
the velocity-dependent turbulence coefficient parameter could represent the resistance to flow
ii
by the water, in contrast to the frictional rheology where resistance is governed only by basal
friction angle.
In Lake Wānaka, newly collected bathymetric and sub-bottom data reveal comparatively few
deposits on the lakebed (n=17), in contrast to the large number of subaerial deposits mapped
and identified within the terrestrial catchment in this thesis (n=202). Limited subsurface
penetration precludes identifying more deposits within the lake infill. Sub-bottom data do reveal
that some of the visible deposits within the lake are draped by lake sediments, obscuring their
true thicknesses. Therefore, burial of deposits may be obscuring the total number of deposits
within the lake basin. The research presented within this thesis builds a proposed conceptual
model for landslide distributions in New Zealand lakes and fjords. Landslides may occur more
frequently in areas of frequent and strong seismicity. In contrast, regions with low frequency
seismicity will likely trigger fewer landslides into, and within the subaqueous basins less often.
Variations in sedimentation rates within the lakes and fjords control how long deposits will be
visible on the basin floors for. Furthermore, the newly identified deposits, and quantitative
insights into the landslide emplacement dynamics provide information that can be taken
forward to assess tsunami hazard, which may present the greatest risk to shoreline communities
and infrastructure around New Zealand lakes and fjords.Iapetus Natural Environment Research Council Doctoral Training
Partnership, and my CASE Partner, the British Geological Survey University Funding Initiative
PhD studentshi
Multiscale modelling and structure-guided development of small molecules tackling neuroinflammation and inflammageing
Full text linkPh. D. ThesisEarly diagnosis and treatment of neurodegenerative diseases has gained attention, given their
increasing prevalence. Multiple proteins are currently being investigated as novel targets for
drug development, including α7 nicotinic receptors and mitochondrial translocator protein
TSPO. These proteins play an important role in neuroinflammation, which makes them
attractive for development of drugs and diagnostics. However, small molecule development has
been hampered by existence of a human-specific dupa7 isoform, and an A147T-TSPO
polymorph, which present a challenge for development of potent and selective ligands.
In this work, I characterised the structure and dynamics of the most plausible functional a7
pentamers bearing dupα7 subunits. The receptors have been modelled and assessed using
multiscale molecular dynamics (MD) simulations and enhanced sampling techniques. The
energy landscapes of the pentamers with different stoichiometries showed that receptors with a
low ratio of dupα7/α7 remained functional. Sensitivity of dupa7 receptors to an antagonist (α-
BTX) and amyloid Aβ42 has also been assessed.
Further, putative “druggable” binding sites at dupα7 receptors were mapped, and interactions
between dupα7 and small molecules were explored using a combination of solvent mapping,
MD simulations, and molecular docking. Results indicated that neither established orthosteric
agonist nor allosteric ligands can bind to dupα7/dupα7 interfaces, however, α7/dupα7 interfaces
remain “druggable”. In addition, several novel allosteric sites were detected on α7/dupα7
receptors. The final part of this work focused on development of novel tracers for A147T-TSPO
variant. Using a combination of molecular modelling, MD simulations, and structure-guided
drug design, I have evaluated plausible binding modes of established TSPO ligands to A147TTSPO.
Results explain the origins of diminished affinity of some established TSPO ligands to
A147T-TSPO. Moreover, I have identified the position of fluorine atom, which is a derivative
of DPA-714 compound to bind to A147T-TSPO with sub-nanomolar affinity. The compound,
denoted as MKD, is feasible for the radiosynthesis
The application and impact of a public health intervention supported by a speech and language therapist in the early years foundation stage
Full text linkPhD ThesisIntroduction
Prevalence estimates indicate up to 50% of children in areas of social deprivation have
speech, language and communication needs (SLCN). Three-tiered service delivery models are
widely recommended to support early communication, however there are few studies
examining the effectiveness of entire multi-tiered systems of support (MTSS).
This thesis presents a longitudinal evaluation of a locally developed MTSS, with two
overarching aims: 1) evaluating the impact of inclusion in this MTSS on vocabulary growth,
and 2) exploring how children with differing SLCN move through the MTSS.
Method
Data about SLC skills, EYFS attainment and social deprivation were collected for 409
participants attending a cluster of school-based nurseries over two years. Participants were
within the control cohort (n=165), the experimental cohort (n=128), or the controlexperimental cohort (n=116). Staff received training and support to implement the MTSS.
Data were analysed to explore distinct patterns through the MTSS. Longitudinal multi-level
modelling was used to explore vocabulary growth and the impact of the MTSS.
Results
Participants followed three distinct pathways: universal tier only, specialist tier only, or
multiple tiers over time. At nursery entry, 100% of participants were below age related
expectations for communication (EYFS) and the mean standard score for receptive vocabulary
(BPVS) was M = 84.9 (SD = 12.2) (n=181). Participants accessing the MTSS gained 2.42 (p<0.05)
additional standard score points per term completed in the MTSS. Those entering nursery
with the lowest vocabulary scores, made the most rapid progress (intercept –slope covariance
-0.70).
Discussion
These results indicate that MTSS within schools can have a positive impact on children’s
vocabulary development. Children entering nursery with the most significant needs can be
supported to begin to close the gap and it is crucial that the universal tier of support is more
than simply ‘business as usual’
Powered Wheelchair Users’ Experiences of Urban Mobility: Researching Access and Disablement through Mobile Methodologies and Digital Technologies
Full text linkPh. D. ThesisInaccessible environments and transportation exclude disabled people from full participation in society. Accessibility is affected by a wide range of socio-material factors, including the interaction between the environment and mobility devices. Yet to date, little research has investigated powered wheelchair users’ experiences of mobility, or how their knowledge might inform policymakers or service providers.
In this thesis, I have worked with powered wheelchair users to document their experiences of mobility and explore how these might be conveyed to other people. An observational go-along method was used, travelling with thirteen participants as they captured their experiences using ‘JourneyCam’, a bespoke smartphone video and data collection tool. The data were used as prompts in semi-structured interviews following each journey. Two further participants were interviewed without first using JourneyCam. Finally, through a series of group workshops, nine participants explored how their collective experiences and knowledge might be used to create more accessible environments.
Powered wheelchair users accumulate situated knowledge which they use to navigate disabling barriers, but this knowledge is gained through significant personal labour and experiences of psycho-emotional disablism. Participants highlighted a wide range of socio-material enablers and disablers to their mobility, including barriers associated with poorly implemented ‘accessibility’ features. However, their efforts to convey their knowledge to service providers were met with indifference, and funnelled through individualised complaints processes. In response participants sought more effective modes of engagement that might bring about systemic change, in line with their commitment to social model principles of confronting structural disablement.
I conclude that not only could powered wheelchair users’ situated knowledge be a valuable resource for service providers and policymakers, but it is also a form of collective resistance to ableist societal practices. The social model of disability remains relevant for disabled people’s efforts to counter disablement, serving as an ‘oppositional device’ that fosters shared resistance.EPSR
Development of a dual sensor polymer-based system for antibiotic detection in water samples
Full text linkPh. D. ThesisIn April 2019, the UN issued a warning that the overuse of antibiotics could lead to 10 million fatalities
annually by 2050. It would also be a significant financial burden as there can be losses of €1.6 billion per
single strain of antimicrobial resistant (AMR) bacteria, occurring primarily but not limited to the costs of
medical care, hospitalisation, and patient care. Infiltration of antibiotics into groundwater arises from
multiple sources; agriculture, highly populated residential areas and pharmaceutical effluents. These
leached antibiotics journey to river systems cause selective pressure, thereby giving rise to accelerated
AMR development. One route for aiding this issue is to slow the growth rate the emergence of AMR by
controlling the levels of antibiotics that gain entry to water systems. To monitor this, a low-cost and reliable
sensor platform is needed that can rapidly and on-site identify contaminated areas. Molecularly Imprinted
Polymers (MIPs) are synthetic receptors that have potential for specific detection of contaminants in
complicated matrices but have found limited commercial applications.
The work within this thesis will explore the rational design of MIPs, their optimisation for a plethora of
targets and the investigation of various applications to exploit their favourable characteristics when
deployed as sensor platforms. Looking at how these imprinted polymers have been developed and utilised
in recent times (primarily 2010-2020) and assessing any limitations encountered. These limitations have
holstered MIP use, giving rise to the need for the critical review, which has been carried out in this thesis,
on what development is needed to boost their applications to convert them into a mainstream commercial
tool.
Most MIP-based sensor systems focus primarily on a single analysis technique. Chapter 3 sees a novel,
dual detection system developed which facilitates direct validation of the results and therefore can realise
reliable detection of antibiotics in aqueous samples. Fluorescent monomers have been incorporated into
the MIP complex allowing for fluorescent analysis as well as thermal, producing a dual sensor platform
thus vastly enhancing the reliability of the biosensor.
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Two applications of MIPs, that have been deployed as sensors, have been experimentally assessed. A
focus on mounting these polymers onto Screen Printed Electrodes (SPEs) and the subsequent thermal
analysis will be describe in chapter 4. This work comprised of a comparison of two techniques was carried
out to determine the most appropriate method for attaching the polymers to the surface of the SPE, direct
polymerisation onto the SPE against dropcasting of MIP particles synthesized by free radical
polymerisation on the SPE surface. The direct polymerisation proved to afford MIP-modified SPEs to
have higher levels of binding affinity. Chapter 5 explores an investigation into the evolution from small
molecule targets to large macromolecules including whole bacteria. This proof-of-concept study saw a
yeast mixture used as a target for MIP detection since yeast resembles bacteria in size and shape but does
not need to be handled in a certified biosafety lab.
A full evaluation of the work carried out concludes the thesis with an aim to gauge how the work
undertaken will contribute to the development of a new division of quantitative sensor platforms.
Secondly, the work produced will construct foundations for what is still needed to push the use of MIPs
into commercial use to combat the rise in AMRManchester Metropolitan Universit
The role of expectations on affective sound processing: behavioural and neural correlates
Full text linkPh. D. Thesis.Theoretical frameworks and empirical evidence in the last two decades have shown that
prior expectations about the upcoming stimulus can shape the perception when the stimulus
arrives. How expectations influence emotional responses to the stimulus is, however, relatively
less understood. In this thesis, using behavioural and neural measures of
electroencephalography (EEG) and intracranially recorded local field potentials (LFPs) from
human subjects, I explore the role of expectations on the processing of affective sounds.
In Chapter 2, the neural basis of expectation is first established using EEG. Two visual cues
were used to elicit the expectation of either neutral or aversive sounds. An event related
potential just before the onset of upcoming stimuli, called Stimulus Preceding Negativity (SPN),
is measured to index the expectation of an upcoming stimulus. Although a robust measure of
SPN could be observed for the expectation of both aversive and neutral sounds, no difference
between the two was observed indicating no relation between the magnitude of SPN and
valence of sounds. Source localization of SPN, using multiple sparse priors algorithm revealed
a network of brain areas including the anterior insula, inferior frontal gyrus, temporal cortex,
supplementary motor area (SMA) and thalamus.
A limitation of the first experiment was that no behavioural measure of expectation of
valence was recorded. It is likely that there is variation across subjects in the expectation and
perceived valence after the stimulus onset. The second experiment (Chapter 3), also a cued
paradigm as above, addressed this limitation by using subjective measures of expectations
before the sound onset and aversive ratings after sound offset as reported by the subjects.
Mediation analysis between perceived ratings following sound onset and expectation ratings
confirmed a mediator role of expectation/predictions in the aversive experience – an
expectation for aversive sounds translated into a more aversive experience, and an expectation
for less aversive sounds translated into a less aversive experience once the sound was heard.
Exploratory analyses showed that subjects whose perceived aversiveness shifted in the
direction of expectation displayed a stronger SPN. Moreover, this effect was seen for aversive
but not for neutral sounds. Additionally, activity in the alpha-beta band during encoding of the
predictive cues was associated with the precision of subjective expectancy. In summary, the
data highlight the importance of measuring behavioural/subjective correlates of expectation
and perceived aversiveness. This may be particularly important when the cues-contingencies
are not explicitly disclosed and when using emotional (subjective) stimuli, as there is bound to
be high inter-individual variability both in learning rates and stimulus appraisal.
Expectations about the upcoming stimulus can be formed based on different sources. For
example, it could be based on information from other people (that is, social source) or
expectations can be formed based on personal experiences with the world (conditioned
source). In the third and last experiment (Chapter 4), the behavioural, physiological and neural
basis of social and conditioned expectations are measured. Using a cued paradigm, subjects
formed expectations of the upcoming stimulus either based on social information or their own
conditioning experiences. As in the experiment in Chapter 3, subjects rated their expectation
prior to the stimulus onset and their perceived aversiveness following the onset of the
stimulus. The data again show that the perceived aversiveness shifted in the direction of
expectations for both the social and conditioned cues. Further, physiological and autonomic
responses also shifted in the direction of expectations. Recordings from LFPs in a group of
epileptic patients undergoing neurosurgical evaluations for the locations of their seizure foci
show expectation-based changes during sound perception in a widespread network including
temporal cortex, anterior cingulate and orbitofrontal cortices, inferior frontal gyrus, and insula.
Collectively, the research presented in this doctoral thesis show expectations can and do
alter the processing of aversive sounds at the behavioural, somatic, and neural levels.Newcastle Universit