FMRI and ERP investigations of body representations in the human lateral and ventral occipitotemporal cortex

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Characterisation of the Haemodynamic Response Function (HRF) in the neonatal brain using functional MRI

Background: Preterm birth is associated with a marked increase in the risk of later neurodevelopmental impairment. With the incidence rising, novel tools are needed to provide an improved understanding of the underlying pathology and better prognostic information. Functional Magnetic Resonance Imaging (fMRI) with Blood Oxygen Level Dependent (BOLD) contrast has the potential to add greatly to the knowledge gained through traditional MRI techniques. However, it has been rarely used with neonatal subjects due to difficulties in application and inconsistent results. Central to this is uncertainity regarding the effects of early brain development on the Haemodynamic Response Function (HRF), knowledge of which is fundamental to fMRI methodology and analysis. Hypotheses: (1) Well localised and positive BOLD functional responses can be identified in the neonatal brain. (2) The morphology of the neonatal HRF differs significantly during early human development. (3) The application of an age-appropriate HRF will improve the identification of functional responses in neonatal fMRI studies. Methods: To test these hypotheses, a systematic fMRI study of neonatal subjects was carried out using a custom made somatosensory stimulus, and an adapted study design and analysis pipeline. The neonatal HRF was then characterised using an event related study design. The potential future application of the findings was then tested in a series of small experiments. Results: Well localised and positive BOLD functional responses were identified in neonatal subjects, with a maturational tendency towards an increasingly complex pattern of activation. A positive amplitude HRF was identified in neonatal subjects, with a maturational trend of a decreasing time-to-peak and increasing positive peak amplitude. Application of the empirical HRF significantly improved the precision of analysis in further fMRI studies. Conclusions: fMRI can be used to study functional activity in the neonatal brain, and may provide vital new information about both development and pathology

Change blindness: eradication of gestalt strategies

Arrays of eight, texture-defined rectangles were used as stimuli in a one-shot change blindness (CB) task where there was a 50% chance that one rectangle would change orientation between two successive presentations separated by an interval. CB was eliminated by cueing the target rectangle in the first stimulus, reduced by cueing in the interval and unaffected by cueing in the second presentation. This supports the idea that a representation was formed that persisted through the interval before being 'overwritten' by the second presentation (Landman et al, 2003 Vision Research 43149–164]. Another possibility is that participants used some kind of grouping or Gestalt strategy. To test this we changed the spatial position of the rectangles in the second presentation by shifting them along imaginary spokes (by ±1 degree) emanating from the central fixation point. There was no significant difference seen in performance between this and the standard task [F(1,4)=2.565, p=0.185]. This may suggest two things: (i) Gestalt grouping is not used as a strategy in these tasks, and (ii) it gives further weight to the argument that objects may be stored and retrieved from a pre-attentional store during this task

Relationships between human auditory cortical structure and function

The human auditory cortex comprises multiple areas, largely distributed across the supratemporal plane, but the precise number and configuration of auditory areas and their functional significance have not yet been clearly established. In this paper, we discuss recent research concerning architectonic and functional organisation within the human auditory cortex, as well as architectonic and neurophysiological studies in non-human species, which can provide a broad conceptual framework for interpreting functional specialisation in humans. We review the pattern in human auditory cortex of the functional responses to various acoustic cues, such as frequency, pitch, sound level, temporal variation, motion and spatial location, and we discuss their correspondence to what is known about the organisation of the auditory cortex in other primates. There is some neuroimaging evidence of multiple tonotopically organised fields in humans and of functional specialisations of the fields in the processing of different sound features. It is thought that the primary area, on Heschl's gyrus, may have a larger involvement in processing basic sound features, such as frequency and level, and that posterior non-primary areas on the planum temporale may play a larger role in processing more spectrotemporally complex sounds. Ways in which current knowledge of auditory cortical organisation and different data analysis approaches may benefit future functional neuroimaging studies which seek to link auditory cortical structure and function are discussed

Mental rotation in Williams syndrome: an impaired imagery ability

Typically developing young children and individuals with intellectual disabilities often perform poorly on mental rotation tasks when the stimulus they are rotating lacks a salient component. However, performance can be improved when salience is increased. The present study investigated the effect of salience on mental rotation performance by individuals with Williams syndrome. Individuals with Williams syndrome and matched controls were presented with two versions of a mental rotation task: a no salient component condition and a salient component condition. The results showed that component salience did not benefit individuals with Williams syndrome in the same manner as it did controls

Common Cortical Loci Are Activated during Visuospatial Interpolation and Orientation Discrimination Judgements

There is a wealth of literature on the role of short-range interactions between low-level orientation-tuned filters in the perception of discontinuous contours. However, little is known about how spatial information is integrated across more distant regions of the visual field in the absence of explicit local orientation cues, a process referred to here as visuospatial interpolation (VSI). To examine the neural correlates of VSI high field functional magnetic resonance imaging was used to study brain activity while observers either judged the alignment of three Gabor patches by a process of interpolation or discriminated the local orientation of the individual patches. Relative to a fixation baseline the two tasks activated a largely over-lapping network of regions within the occipito-temporal, occipito-parietal and frontal cortices. Activated clusters specific to the orientation task (orientation>interpolation) included the caudal intraparietal sulcus, an area whose role in orientation encoding per se has been hotly disputed. Surprisingly, there were few task-specific activations associated with visuospatial interpolation (VSI>orientation) suggesting that largely common cortical loci were activated by the two experimental tasks. These data are consistent with previous studies that suggest higher level grouping processes -putatively involved in VSI- are automatically engaged when the spatial properties of a stimulus (e.g. size, orientation or relative position) are used to make a judgement

The Molecular-enriched Functional Circuits Underlying Consciousness and Cognition

Homo Sapiens consist of trillions of atoms, each inanimate, yet somehow collectively constituting a conscious being. The fundamental question of how organisms are organised to beget consciousness and cognition has largely been approached through independent examination of the structure and function of the nervous system at varying levels of granularity. As neuroscience progresses, it has thus increasingly fragmented into separate streams of research which study the brain at these different scales. This has resulted in the field becoming “data rich, but theory poor”, which is largely attributable to the paucity of methods which bridge these levels of analysis to provide novel trans-hierarchical insights and inform unified theories. The research in this doctoral thesis therefore aims to explore how a specific type of multimodal analysis - Receptor-Enriched Analysis of functional Connectivity by Targets (REACT) – can begin to bridge the theoretic void between molecular level mechanisms and systems levels dynamics to provide novel perspectives on the function and dysfunction of the brain. First, I provide a narrative synthesis of the challenges precluding a meaningful understanding of the human brain utilising conventional functional neuroimaging and outlining how incorporation of molecular information may help overcome these limitations. Specifically, by embedding functional dynamics in the molecular landscape of the brain, we can begin to move from the simple characterisation of “where” cognitive phenomena may be within the brain towards mechanistic accounts of “how” they are produced. Additionally, this offers enticing opportunities to link pharmacological treatments to novel molecular-network based biomarkers. Second, I explore how networks enriched with the spatial configurations of serotonergic and dopaminergic receptor subtypes are modulated by lysergic acid diethylamide (LSD) as compared to placebo in healthy participants. The results highlight the challenges of disentangling pharmacodynamics of drugs exhibiting rich pharmacology as well as identifying differential relationship between serotonergic and dopaminergic networks and phenomenological sub- components of psychedelic state. Third, I expand the remit of molecular-enriched network analyses beyond pure psychopharmacology to examine the direct and indirect actions of propofol anaesthesia on inhibitory and modulatory neurotransmission at both rest as well as during a naturalistic listening task. This work demonstrates for the first time that these molecular-networks can capture broader perceptual and cognitive-driven network reconfigurations as well as indirect pharmacological actions on neuromodulatory systems. Moreover, it provides evidence that the effects of propofol on consciousness are enacted through both direct inhibitory as well as indirect neuromodulatory mechanisms.Finally, I produce normative models of networks enriched with the principal neuromodulatory, excitatory, and inhibitory transmitter systems, testing their capacity to characterise neural dysfunction within and across several neuropsychiatric disorders. This work provides a computational foundation for large scale integration of molecular mechanisms and functional imaging to provide novel individualised biomarkers for neuropsychiatric disorders. Collectively, this thesis offers methodological and theoretical progress towards a trans-hierarchical characterisation of the human brain, providing insights into the neural correlates of both conscious contents and level as well as the perturbations underlying key neuropsychiatric conditions