201 research outputs found
A neuroimaging investigation of bipolar disorder and the neurocognitive effects of 5-HT7 antagonists
Bipolar disorder is a psychiatric disorder characterised by pathological mood states, but there is growing recognition of the role of cognitive impairment and dysfunction of emotional processes, which has a profound impact on quality of life. Many people with bipolar disorders exhibit brain volume impairment associated with cognitive dysfunction and an increased risk of dementia. In this thesis, I conducted a systematic review to understand the relationships between mood disorders and the 5-HT7 receptor. The 5-HT7 receptor is related to depression and anxiety, but the relationship between 5-HT7 and mania remains unclear; in addition, sleep and memory were also related to the 5-HT7 receptor. Followed by these findings, in the next two chapters, I examined the effects of 5-HT7 antagonists, using JNJ-18038683, on emotional and cognitive functioning, as well as their neural substrates. I then reported on neuroimaging investigations examining the effects of 5-HT7 antagonists on emotional processing and cognitive function in healthy volunteers to gain insight into their potential mode of action and utility for bipolar disorder. In fMRI analyses, the drug acted on 5-HT7 receptors potentially improving cognitive performance by modulating the function of the Cognitive Control Network in healthy controls. In the above-mentioned chapters, I gained a better understanding of the 5-HT7 antagonist, JNJ-18038683, and the putative promising effects for pharmacological treatments. However, the approach taken has some limitations, including a small sample size, potential participant bias, and a lack of systematic control of medication dose and duration of administration. In addition, in Chapter 5, I explored the brain basis of bipolar disorder and its links to cognitive and emotional dysfunction using a new ‘brain age’ approach. Individuals with bipolar disorder were found to have increased brain age compared to healthy controls. I hope that these findings can be applied to pharmacological treatment for individuals with bipolar disorder, ultimately allowing patients to benefit from the drug in the future
A Spark Of Emotion: The Impact of Electrical Facial Muscle Activation on Emotional State and Affective Processing
Facial feedback, which involves the brain receiving information about the activation of facial muscles, has the potential to influence our emotional states and judgments. The extent to which this applies is still a matter of debate, particularly considering a failed replication of a seminal study. One factor contributing to the lack of replication in facial feedback effects may be the imprecise manipulation of facial muscle activity in terms of both degree and timing. To overcome these limitations, this thesis proposes a non-invasive method for inducing precise facial muscle contractions, called facial neuromuscular electrical stimulation (fNMES). I begin by presenting a systematic literature review that lays the groundwork for standardising the use of fNMES in psychological research, by evaluating its application in existing studies. This review highlights two issues, the lack of use of fNMES in psychology research and the lack of parameter reporting. I provide practical recommendations for researchers interested in implementing fNMES. Subsequently, I conducted an online experiment to investigate participants' willingness to participate in fNMES research. This experiment revealed that concerns over potential burns and involuntary muscle movements are significant deterrents to participation. Understanding these anxieties is critical for participant management and expectation setting. Subsequently, two laboratory studies are presented that investigated the facial FFH using fNMES. The first study showed that feelings of happiness and sadness, and changes in peripheral physiology, can be induced by stimulating corresponding facial muscles with 5–seconds of fNMES. The second experiment showed that fNMES-induced smiling alters the perception of ambiguous facial emotions, creating a bias towards happiness, and alters neural correlates of face processing, as measured with event-related potentials (ERPs). In summary, the thesis presents promising results for testing the facial feedback hypothesis with fNMES and provides practical guidelines and recommendations for researchers interested in using fNMES for psychological research
Analytical validation of innovative magneto-inertial outcomes: a controlled environment study.
peer reviewe
Relationship between Anxiety and Freezing of Gait
Parkinson’s disease (PD) is the second most common neurodegenerative and a large percentage of PD patients develop freezing of gait (FOG) leading to an overall reduced quality of life. The overarching aim of the thesis is to investigate the relationship between anxiety and freezing of gait, to extend current research on this topic and produce findings that could facilitate more adequate treatment methods for this symptom.
The first study validated the seated functional MRI-compatible version of the walking threat paradigm that was previously found to induce anxiety and FOG. This would enable future studies to examine the neural correlates behind anxiety-induced freezing of gait. The second study investigated the effect of anxiety on the utilisation of body-related visual feedback in the form of an avatar in the virtual environment to improve FOG. The third study investigated the effects of Levodopa on the fronto-striato-limbic circuitry in PD Freezers at rest in their ‘ON’ and ‘OFF’ dopaminergic state.
Findings suggest that the VR seated threat paradigm is an adequate behavioural surrogate for the VR walking threat paradigm, eliciting comparable amounts of anxiety and freezing of gait as the walking version. Anxiety was also found to interfere with the utilisation of sensory feedback to improve FOG, where in highly threatening situations Freezers lack the capacity to process visual feedback for gait. Finally, dopaminergic medication was also found to partially modulate the frontoparietal-limbic-striatal circuitry in PD Freezers, where baseline anxiety levels influence the impact of Levodopa on the frontoparietal (FPN)- limbic connectivity, and the FPN-putamen connectivity.
In conclusion, the current thesis suggests that anxiety contributes to freezing of gait, which may present a barrier to treatment and could be a key factor in the heterogeneity observed in response to medication and sensory cueing
New techniques for neuro-rehabilitation: Transcranial Electric Stimulation and Virtual Reality
Recovery of motor and cognitive performances after a neurological illness remains a significant challenge for rehabilitation specialists. The traditional rehabilitative interventions are usually delivered using a multidisciplinary
approach, whose results are not always satisfactory. These limitations in functional recovery have led researchers
to consider alternative approaches. The hypothesis of providing new therapeutic possibilities in
the different patients treated is, as a rehabilitator, very rewarding and represents a challenge for the future. The application of simple and low-cost techniques, defined by the literature as "unconventional" or “novel”, can provide new ideas not only in the field of research but above all of application in clinical reality.A suitable approach to improve the rehabilitation outcome is to utilize these novel rehabilitation techniques that act as a substitute or an addition to the traditional ones. In this context, some recent approaches have been proposed that might increase the effectiveness of a traditional treatment. Among them, two techniques have been demonstrated to be very promising, namely non-invasive brain stimulation (NIBS) and Virtual Reality (VR).In light of the foregoing, my thesis has been divided into two main lines of research, namely: a) the study of the effects of transcranial direct current stimulation (tDCS) in different neurological conditions; b) the application of VR (used alone or combined with tDCS) in the treatment of some neurocognitive disorders. A semi-immersive VR tool (ReMOVES system) has been used as
a user-friendly platform providing activities based on exergames
Temporal Associations between Regional Sleep Spindles and Slow Oscillations during NREM Sleep in Older Adults with and without Mild Cognitive Impairment
Sleep is acknowledged as an emerging modifiable risk factor for dementia. Sleep spindles and slow oscillations are distinct electroencephalographic (EEG) features of non-rapid eye movement (NREM) sleep. Deficiencies in these neuro-oscillations, as well as their temporal coordination have been linked to impairments in sleep-dependent memory consolidation. Mild cognitive impairment (MCI), considered the prodromal stage of dementia, may present a window of opportunity for targeted intervention. Sleep structure abnormalities have been reported in MCI, including some evidence to suggest deficits in sleep spindle and slow wave activities. Preliminary evidence additionally demonstrates how the co-occurrence or coupling of slow oscillations and sleep spindles may also contribute to sleep-dependent memory consolidation. However, it is currently unclear whether changes in the coupling between slow oscillations and sleep spindles are present in MCI. The present study investigates the regional differences in slow oscillation-sleep spindle (SO-SP) coupling between older adults with MCI and cognitively-intact controls, and the associations between coupling strength and overnight memory consolidation.
This thesis is the first to compare SO-SP coupling, as well as explore the relationship between coupling and sleep-dependent memory consolidation in older adults with and without MCI. Findings suggest that regional deficits in spindle activity are present in older adults at risk of dementia development, and may thus provide potential utility as a sleep biomarker of impaired overnight memory processing. High-density EEG provides high spatial sensitivity to investigate localised changes in NREM sleep neuro-oscillatory activity. Future multi-modal brain imaging studies may elucidate underlying regional brain pathology linked to altered sleep neurophysiology, SO-SP coupling dynamics and sleep-dependent memory consolidation processes in this prodromal group
New insights on the multidimensionality of fatigue and on its relationship with cognitive impairments in multiple sclerosis
Multiple Sclerosis (MS) is an inflammatory disease of the central nervous system (CNS), and it represents the most common cause of irreversible impairment in young adults, affecting about 2.5 million individuals worldwide. In MS, acute attacks of inflammation, leading to demyelination and axonal loss, determine the accumulation of disabilities, varying in number, nature, and severity. Indeed, motor, sensory, cognitive, and behavioral symptoms may manifest at different times during the disease's variable clinical course.
Fatigue is a complex and multifaceted phenomenon and one of the most prevalent and disabling symptoms of MS, affecting 75%–90% of patients. Despite its prevalence, MS- related fatigue is still poorly understood. The absence of a well-validated definition and of clear insights into its pathophysiological causes makes fatigue a hybrid symptom, approached within the context of different disciplines, each with their own methods and tools. As a result, the scientific literature abounds with irreconcilable data, leaving fatigue in a dark shadow zone, at the expense of MS patients still lacking adequate therapies and strategies of management.
The main topic of this thesis relates to the multidimensional nature of fatigue, to its variability, and its effects on attentional processes, most commonly affected in MS patients. Specifically, studies presented in the current thesis address four research issues:
(i)
are physical and mental fatigue two distinct constructs?
(ii)
how do physical and mental fatigue vary within a short (within a day) and long (within a year) period?
(iii)
how do induced physical and mental fatigue impact the attentional functions of alerting, orienting, and conflict resolution in MS?
The main results of the studies are reported:
a)
A clear distinction between physical and mental fatigue has been psychometrically documented in MS patients.
b)
MS patients reported experiencing more overall fatigue than Controls.
c)
A gradual increase in overall fatigue from the morning to the evening was reported by MS participants.
d)
Across experiments physical fatigue was significantly more pronounced in MS
patients as compared to Controls.
e)
Both MS patients and Controls reported having experienced more overall fatigue in the past (one year ago) than in the present (the last 24 hours).
f)
MS patients were slower as compared to Controls in performing attentional tasks; however, inconclusive results have emerged regarding the effects of physical and mental fatigue on attentional processes.
g)
Sleep quality and depression were both associated with fatigue across the experiments. The relationship between self-efficacy, general cognitive functioning, functional deterioration, and physical and mental fatigue is fragmented, thus preventing a clear conclusion
Exploring neural markers of language processing using fNIRS in typically developed children and children with Developmental Language Disorder
Background: Developmental language disorder (DLD) is a life-long condition with no clear biological causes that affects approximately 8% of the population. The diagnosis currently relies on behavioural testing that is not reliably performed on children younger than school age. Consequently, the diagnosis and treatment of DLD is often delayed until after children enter formal education. Early work in the field suggests that neural markers of language processing could be used to develop an objective diagnostic tool that will allow for accurate and early identification of DLD in preschool years and thus access to early interventions. Here we propose the use of a novel non-invasive neuroimaging technique called functional near infrared spectroscopy (fNIRS) to identify neural markers of language processing in children with DLD. Additionally, we argue that to understand atypical language processing, it is imperative to also investigate typical cortical activations in response to language processing to establish the developmental trajectories of the language network. Parallel to these studies we also investigate patterns of neural synchrony during parent-child interactions. Speech and language development in children is thought to rely on successful parent-child interactions, however, little is known regarding the underlying neural mechanisms from which they arise.
Methods: Cross-Sectional fNIRS Studies: A total of 36 participants aged 6–16-year-old (1 participant with DLD) were recruited in two cross-sectional fNIRS studies. Participants underwent a 10-minute resting state imaging session and completed a series of computer-administered language and cognitive tasks while their brain activity was recorded using fNIRS from the bilateral inferior frontal gyrus (IFG) and the bilateral auditory cortices. Hyperscanning fNIRS Study: 12 children aged between 3 and 5 years old and their mothers participated in this study. Neural synchrony in mother-child dyads was measured bilaterally over frontal and temporal areas using fNIRS whilst the dyads were asked to play together (interactive condition) and separately (independent condition). Communication patterns were captured via video recordings and conversational turns were coded.
Survey Study: 43 parents of children with DLD and 44 clinicians with DLD expertise completed a qualitative online survey detailing their views, concerns and recommendations regarding the use of neuroimaging-based tool for the diagnosis and monitoring of DLD.
Results: Cross sectional fNIRS studies: In typically developed children and adolescents, widespread connections between the language regions and the right IFG appear to continue decreasing as age increases. In contrast connections between temporal regions are well established by late childhood. Increased activity over right auditory regions is associated with decreased language skills. Whilst data from the DLD participant is described, further analysis was not possible due to the limited sample size (n=1). Hyperscanning fNIRS study: We successfully recorded inter-brain synchrony in bilateral prefrontal and temporal cortices in mother-child dyads while they engaged in cooperative and independent play. Compared to the independent condition, mother-child dyads showed increased neural synchrony in the interactive condition across the prefrontal cortex and temporo-parietal junction. There was no significant relationship found between neural synchrony and turn-taking, but neural synchrony was negatively correlated with the child’s levels of surgency.
Survey study: Clinicians and parents perceived that a potential tool that could diagnose children with DLD earlier would positively impact the children as it would allow them to access interventions earlier. This study offered a unique account of the factors to be considered in the design and implementation of clinical measures for language disorders from the viewpoints of parents and language professionals.
Conclusions: Overall, this research aimed to identify neural markers of language processing in children with DLD and typically developed children to help develop an objective early diagnostic tool. Ultimately, this research might help maximize the benefits of speech and language therapies to improve the quality of life for children with DLD. This can be very impactful translational research in language development given that currently no objective neural-based tools exist for DLD
Investigating self-perception of emotion in individuals with non-epileptic seizures (NES)
Emotional processing difficulties are hypothesised to be involved in the aetiology and maintenance of non-epileptic seizures (NES). This thesis aimed to explore the relationship between aspects of emotional processing: interoception, alexithymia and executive functioning, in people with NES in comparison with healthy controls and to understand how people with NES experience their symptoms, live with their condition, and perceive the role of life events in relation to their seizures.
Study 1 reviewed the evidence for a relationship between interoception and other key emotional factors in studies which employed heartbeat perception tasks to measure interoception. Study quality was found to be generally poor, with no consistent evidence for significant findings between interoception and emotional factors, including alexithymia, depression, and anxiety.
Study 2 was a cross-sectional, online, study to investigate an interactional model of emotion processing, exploring relationships between interoceptive sensibility, alexithymia, and executive functioning (attentional bias) in NES participants and healthy controls. Measures included the Body Perception Questionnaire (BPQ-VSF), the Toronto Alexithymia Scale-20 (TAS-20) and the emotional Stroop task (eStroop). The NES group, compared to controls, reported higher BPQ-VSF and TAS-20 scores. There were no significant correlations between any of the measures of interest in either the NES or control group. There was no evidence to support the proposed model.
Study 3 was a qualitative study using Interpretative Phenomenological Analysis to explore: how individuals with NES respond emotionally to recent life events; and how these events impact on seizures. Six themes were developed from the analysis which described how NES affected many aspects of people’s lives. Four models captured the different ways in which people perceived the relationship between life stressors, their emotional responses, and their seizures: event->emotional response-> seizure; event-> emotional response -x-> no seizure; no event ->emotional reaction/experience -> seizure; and no event -x->no emotional response->seizure
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