2,068 research outputs found

    Scene-selectivity in CA1/subicular complex: Multivoxel pattern analysis at 7T

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    Prior univariate functional magnetic resonance imaging (fMRI) studies in humans suggest that the anteromedial subicular complex of the hippocampus is a hub for scene-based cognition. However, it is possible that univariate approaches were not sufficiently sensitive to detect scene-related activity in other subfields that have been implicated in spatial processing (e.g., CA1). Further, as connectivity-based functional gradients in the hippocampus do not respect classical subfield boundary definitions, category selectivity may be distributed across anatomical subfields. Region-of-interest approaches, therefore, may limit our ability to observe category selectivity across discrete subfield boundaries. To address these issues, we applied searchlight multivariate pattern analysis to 7T fMRI data of healthy adults who undertook a simultaneous visual odd-one-out discrimination task for scene and non-scene (including face) visual stimuli, hypothesising that scene classification would be possible in multiple hippocampal regions within, but not constrained to, anteromedial subicular complex and CA1. Indeed, we found that the scene-selective searchlight map overlapped not only with anteromedial subicular complex (distal subiculum, pre/para subiculum), but also inferior CA1, alongside posteromedial (including retrosplenial) and parahippocampal cortices. Probabilistic overlap maps revealed gradients of scene category selectivity, with the strongest overlap located in the medial hippocampus, converging with searchlight findings. This was contrasted with gradients of face category selectivity, which had stronger overlap in more lateral hippocampus, supporting ideas of parallel processing streams for these two categories. Our work helps to map the scene, in contrast to, face processing networks within, and connected to, the human hippocampus

    A neuroimaging investigation of bipolar disorder and the neurocognitive effects of 5-HT7 antagonists

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    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

    Addiction in context

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    The dissertation provides a comprehensive exploration of the interplay between social and cultural factors in substance use, specifically focusing on alcohol use disorder (AUD) and cannabis use disorder (CUD). It begins by introducing the concept of social plasticity, which posits that adolescents' susceptibility to AUD is influenced by their heightened sensitivity to their social environment, but this sensitivity increases the potential for recovery in the transition to adulthood.A series of studies delves into how social cues impact alcohol craving and consumption. One study using functional magnetic resonance imaging (fMRI) investigated social alcohol cue reactivity and its relationship to social drinking behavior, revealing increased craving but no significant change in brain activity in response to alcohol cues. Another fMRI study compared social processes in alcohol cue reactivity between adults and adolescents, showing age-related differences in how social attunement affects drinking behavior. Shifting focus to cannabis, this dissertation discusses how cultural factors, including norms, legal policies, and attitudes, influence cannabis use and processes underlying CUD. The research presented examined various facets of cannabis use, including how cannabinoid concentrations in hair correlate with self-reported use, the effects of cannabis and cigarette co-use on brain reactivity, and cross-cultural differences in CUD between Amsterdam and Texas. Furthermore, the evidence for the relationship between cannabis use, CUD, and mood disorders is reviewed, suggesting a bidirectional relationship, with cannabis use potentially preceding the onset of bipolar disorder and contributing to the development and worse prognosis of mood disorders and mood disorders leading to more cannabis use

    Using Image Translation To Synthesize Amyloid Beta From Structural MRI

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    Amyloid-beta and brain atrophy are known hallmarks of Alzheimer’s Disease (AD) and can be quantified with positron emission tomography (PET) and structural magnetic resonance imaging (MRI), respectively. PET uses radiotracers that bind to amyloid-beta, whereas MRI can measure brain morphology. PET scans have limitations including cost, invasiveness (involve injections and ionizing radiation exposure), and have limited accessibility, making PET not practical for screening early-onset AD. Conversely, MRI is a cheaper, less-invasive (free from ionizing radiation), and is more widely available, however, it cannot provide the necessary molecular information. There is a known relationship between amyloid-beta and brain atrophy. This thesis aims to synthesize amyloid-beta PET images from structural MRI using image translation, an advanced form of machine learning. The developed models have reported high-similarity metrics between the real and synthetic PET images and high-degree of accuracy in radiotracer quantification. The results are highly impactful as it enables amyloid-beta measurements form every MRI, for free

    The ins and outs of open-angle Glaucoma:drugs, diet, and defecation

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    Glaucoma is the leading cause of irreversible blindness and second leading cause of blindness. The primary aim of this thesis is to provide insight into the role of systemic effectsin the pathophysiology of OAG.<br/

    Techniques and graft materials for repairing peripheral nerve defects

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    Peripheral nerve defects refer to damage or destruction occurring in the peripheral nervous system, typically affecting the limbs and face. The current primary approaches to address peripheral nerve defects involve the utilization of autologous nerve transplants or the transplantation of artificial material. Nevertheless, these methods possess certain limitations, such as inadequate availability of donor nerve or unsatisfactory regenerative outcomes post-transplantation. Biomaterials have been extensively studied as an alternative approach to promote the repair of peripheral neve defects. These biomaterials include both natural and synthetic materials. Natural materials consist of collagen, chitosan, and silk, while synthetic materials consist of polyurethane, polylactic acid, and polycaprolactone. Recently, several new neural repair technologies have also been developed, such as nerve regeneration bridging technology, electrical stimulation technology, and stem cell therapy technology. Overall, biomaterials and new neural repair technologies provide new methods and opportunities for repairing peripheral nerve defects. However, these methods still require further research and development to enhance their effectiveness and feasibility

    The anatomy of excitement:Understanding and improving the effectiveness of electroconvulsive therapy

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    Electroconvulsive therapy (ECT) is an effective treatment for severe depression. In this thesis, I studied electroconvulsive therapy (ECT) research with the objective to improve the clinical outcome after treatment and to gain a better understanding of its working mechanisms. Multiple methods in ECT research were explored, varying with respect to sample selection (i.e., single- versus multi-center data), study design (i.e., observational retrospective study versus prospective RCT, controlled versus non-controlled), type of data (i.e., clinical, EEG, and [f]MRI), and the applied statistical models to analyze the data (i.e., frequentist versus Bayesian models). Additionally, I proposed a taxonomy of ECT research. The main chapters can be considered as specific case-examples of the child-nodes of this taxonomy. Thereby, this thesis contributes to improving the clinical outcome and understanding of the working mechanisms of ECT. Based on the findings in this thesis, I have discussed the methods that are commonly used in ECT research and which future directions this may take

    Neuroimaging investigations of cortical specialisation for different types of semantic knowledge

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    Embodied theories proposed that semantic knowledge is grounded in motor and perceptual experiences. This leads to two questions: (1) whether the neural underpinnings of perception are also necessary for semantic cognition; (2) how do biases towards different sensorimotor experiences cause brain regions to specialise for particular types of semantic information. This thesis tackles these questions in a series of neuroimaging and behavioural investigations. Regarding question 1, strong embodiment theory holds that semantic representation is reenactment of corresponding experiences, and brain regions for perception are necessary for comprehending modality-specific concepts. However, the weak embodiment view argues that reenactment may not be necessary, and areas near to perceiving regions may be sufficient to support semantic representation. In the particular case of motion concepts, lateral occipital temporal cortex (LOTC) has been long identified as an important area, but the roles of its different subregions are still uncertain. Chapter 3 examined how different parts of LOTC reacted to written descriptions of motion and static events, using multiple analysis methods. A series of anterior to posterior sub-regions were analyzed through univariate, multivariate pattern analysis (MVPA), and psychophysical interaction (PPI) analyses. MVPA revealed strongest decoding effects for motion vs. static events in the posterior parts of LOTC, including both visual motion area (V5) and posterior middle temporal gyrus (pMTG). In contrast, only the middle portion of LOTC showed increased activation for motion sentences in univariate analyses. PPI analyses showed increased functional connectivity between posterior LOTC and the multiple demand network for motion events. These findings suggest that posterior LOTC, which overlapped with the motion perception V5 region, is selectively involved in comprehending motion events, while the anterior part of LOTC contributes to general semantic processing. Regarding question 2, the hub-and-spoke theory suggests that anterior temporal lobe (ATL) acts as a hub, using inputs from modality-specific regions to construct multimodal concepts. However, some researchers propose temporal parietal cortex (TPC) as an additional hub, specialised in processing and integrating interaction and contextual information (e.g., for actions and locations). These hypotheses are summarized as the "dual-hub theory" and different aspects of this theory were investigated in in Chapters 4 and 5. Chapter 4 focuses on taxonomic and thematic relations. Taxonomic relations (or categorical relations) occur when two concepts belong to the same category (e.g., ‘dog’ and ‘wolf’ are both canines). In contrast, thematic relations (or associative relations) refer to situations that two concepts co-occur in events or scenes (e.g., ‘dog’ and ‘bone’), focusing on the interaction or association between concepts. Some studies have indicated ATL specialization for taxonomic relations and TPC specialization for thematic relations, but others have reported inconsistent or even converse results. Thus Chapter 4 first conducted an activation likelihood estimation (ALE) meta-analysis of neuroimaging studies contrasting taxonomic and thematic relations. This found that thematic relations reliably engage action and location processing regions (left pMTG and SMG), while taxonomic relations only showed consistent effects in the right occipital lobe. A primed semantic judgement task was then used to test the dual-hub theory’s prediction that taxonomic relations are heavily reliant on colour and shape knowledge, while thematic relations rely on action and location knowledge. This behavioural experiment revealed that action or location priming facilitated thematic relation processing, but colour and shape did not lead to priming effects for taxonomic relations. This indicates that thematic relations rely more on action and location knowledge, which may explain why the preferentially engage TPC, whereas taxonomic relations are not specifically linked to shape and colour features. This may explain why they did not preferentially engage left ATL. Chapter 5 concentrates on event and object concepts. Previous studies suggest ATL specialization for coding similarity of objects’ semantics, and angular gyrus (AG) specialization for sentence and event structure representation. In addition, in neuroimaging studies, event semantics are usually investigated using complex temporally extended stimuli, unlike than the single-concept stimuli used to investigate object semantics. Thus chapter 5 used representational similarity analysis (RSA), univariate analysis, and PPI analysis to explore neural activation patterns for event and object concepts presented as static images. Bilateral AGs encoded semantic similarity for event concepts, with the left AG also coding object similarity. Bilateral ATLs encoded semantic similarity for object concepts but also for events. Left ATL exhibited stronger coding for events than objects. PPI analysis revealed stronger connections between left ATL and right pMTG, and between right AG and bilateral inferior temporal gyrus (ITG) and middle occipital gyrus, for event concepts compared to object concepts. Consistent with the meta-analysis in chapter 4, the results in chapter 5 support the idea of partial specialization in AG for event semantics but do not support ATL specialization for object semantics. In fact, both the meta-analysis and chapter 5 findings suggest greater ATL involvement in coding objects' associations compared to their similarity. To conclude, the thesis provides support for the idea that perceptual brain regions are engaged in conceptual processing, in the case of motion concepts. It also provides evidence for a specialised role for TPC regions in processing thematic relations (pMTG) and event concepts (AG). There was mixed evidence for specialisation within the ATLs and this remains an important target for future research
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