Studying Cortical Plasticity in Ophthalmic and Neurological Disorders:From Stimulus-Driven to Cortical Circuitry Modeling Approaches

Unsolved questions in computational visual neuroscience research are whether and how neurons and their connecting cortical networks can adapt when normal vision is compromised by a neurodevelopmental disorder or damage to the visual system. This question on neuroplasticity is particularly relevant in the context of rehabilitation therapies that attempt to overcome limitations or damage, through either perceptual training or retinal and cortical implants. Studies on cortical neuroplasticity have generally made the assumption that neuronal population properties and the resulting visual field maps are stable in healthy observers. Consequently, differences in the estimates of these properties between patients and healthy observers have been taken as a straightforward indication for neuroplasticity. However, recent studies imply that the modeled neuronal properties and the cortical visual maps vary substantially within healthy participants, e.g., in response to specific stimuli or under the influence of cognitive factors such as attention. Although notable advances have been made to improve the reliability of stimulus-driven approaches, the reliance on the visual input remains a challenge for the interpretability of the obtained results. Therefore, we argue that there is an important role in the study of cortical neuroplasticity for approaches that assess intracortical signal processing and circuitry models that can link visual cortex anatomy, function, and dynamics

The cognitive neuroscience of visual working memory

Visual working memory allows us to temporarily maintain and manipulate visual information in order to solve a task. The study of the brain mechanisms underlying this function began more than half a century ago, with Scoville and Milner’s (1957) seminal discoveries with amnesic patients. This timely collection of papers brings together diverse perspectives on the cognitive neuroscience of visual working memory from multiple fields that have traditionally been fairly disjointed: human neuroimaging, electrophysiological, behavioural and animal lesion studies, investigating both the developing and the adult brain

Micro-, Meso- and Macro-Dynamics of the Brain

Neurosciences, Neurology, Psychiatr

A working model on large-scale spatio-temporal organization of brain functioning and its implications for bipolar disorder

A working model on large-scale spatio-temporal organization of brain functioning and its implications for bipolar disorde

A survey of visual preprocessing and shape representation techniques

Many recent theories and methods proposed for visual preprocessing and shape representation are summarized. The survey brings together research from the fields of biology, psychology, computer science, electrical engineering, and most recently, neural networks. It was motivated by the need to preprocess images for a sparse distributed memory (SDM), but the techniques presented may also prove useful for applying other associative memories to visual pattern recognition. The material of this survey is divided into three sections: an overview of biological visual processing; methods of preprocessing (extracting parts of shape, texture, motion, and depth); and shape representation and recognition (form invariance, primitives and structural descriptions, and theories of attention)

Oszillatorische Gamma-Band-Aktivität bei der Verarbeitung auditorischer Reize im Kurzzeitgedächtnis im MEG

Recent studies have suggested an important role of cortical gamma oscillatory activity (30-100 Hz) as a correlate of encoding, maintaining and retrieving auditory, visual or tactile information in and from memory. It was shown that these cortical stimulus representations were modulated by attention processes. Gamma-band activity (GBA) occurred as an induced response peaking at approximately 200-300 ms after stimulus presentation. Induced cortical responses appear as non-phase-locked activity and are assumed to reflect active cortical processing rather than passive perception. Induced GBA peaking 200-300 ms after stimulus presentation has been assumed to reflect differences between experimental conditions containing various stimuli. By contrast, the relationship between specific oscillatory signals and the representation of individual stimuli has remained unclear. The present study aimed at the identification of such stimulus-specific gamma-band components. We used magnetoencephalography (MEG) to assess gamma activity during an auditory spatial delayed matching-to-sample task. 28 healthy adults were assigned to one of two groups R and L who were presented with only right- or left-lateralized sounds, respectively. Two sample stimuli S1 with lateralization angles of either 15° or 45° deviation from the midsagittal plane were used in each group. Participants had to memorize the lateralization angle of S1 and compare it to a second lateralized sound S2 presented after an 800-ms delay phase. S2 either had the same or a different lateralization angle as S1. After the presentation of S2, subjects had to indicate whether S1 and S2 matched or not. Statistical probability mapping was applied to the signals at sensor level to identify spectral amplitude differences between 15° and 45° stimuli. We found distinct gamma-band components reflecting each sample stimulus with center frequencies ranging between 59 and 72 Hz in different sensors over parieto-occipital cortex contralateral to the side of stimulation. These oscillations showed maximal spectral amplitudes during the middle 200-300 ms of the delay phase and decreased again towards its end. Additionally, we investigated correlations between the activation strength of the gamma-band components and memory task performance. The magnitude of differentiation between oscillatory components representing 'preferred' and 'nonpreferred' stimuli during the final 100 ms of the delay phase correlated positively with task performance. These findings suggest that the observed gamma-band components reflect the activity of neuronal networks tuned to specific auditory spatial stimulus features. The activation of these networks seems to contribute to the maintenance of task-relevant information in short-term memory.Ergebnisse aus aktuellen Studien legen nahe, dass kortikale oszillatorische Aktivität im Gamma-Bereich (30-100 Hz) eine wichtige Rolle für verschiedene kognitive Prozesse spielt. Dazu zählen das Kodieren, die Aufrechterhaltung und der Abruf auditorischer, visueller oder taktiler Informationen in das bzw. aus dem Gedächtnis. Es konnte gezeigt werden, dass diese kortikale Aktivität durch Aufmerksamkeitsprozesse beeinflusst wird. Gamma-Aktivität trat bei vorangegangenen Untersuchungen als induzierte Antwort ca. 200-300 ms nach Stimuluspräsentation auf. Es wird angenommen, dass diese nicht phasengebundenen kortikalen Reizantworten aktive kortikale Verarbeitungs-prozesse widerspiegeln. In früheren Studien wurde induzierte Gamma-Aktivität während der Aufrechterhaltung von Stimulusinformationen über Regionen gefunden, die an der Verarbeitung aufgabenrelevanter Reizmerkmale beteiligt sind. Diese Antworten im Gamma-Bereich spiegelten Unterschiede zwischen verschieden experimentellen Bedingungen wider, jedoch ist wenig über die Repräsentation spezifischer Stimuluseigenschaften durch Gamma-Aktivität bekannt. Mit der vorliegenden Studie haben wir versucht, solche stimulus spezifischen Gamma-Komponenten zu untersuchen. Dafür verwendeten wir Magnetenzephalographie (MEG) und eine auditorische räumliche “delayed matching-to-sample“ Aufgabe. 28 gesunde Erwachsene wurden dabei zwei verschiedenen Gruppen zugeordnet. Gruppe R bekam rechtslateralisierte Stimuli präsentiert, während diese in Gruppe L linkslateralisiert waren. Dabei unterschieden sich die Reize nur in ihrer räumlichen Charakteristik, die Klangmuster blieben unverändert. In beiden Gruppen wurden zwei Beispielstimuli S1 mit Lateralisierungswinkeln von 15° bzw. 45° verwendet. Die Probanden mussten sich den Lateralisierungswinkel von S1 merken und anschließend mit einem zweiten Stimulus S2, der nach einer Verzögerungsphase von 800 ms präsentiert wurde, vergleichen. S2 hatte dabei entweder den gleichen Lateralisierungswinkel wie S1, oder unterschied sich darin von dem ersten Stimulus. Nach der Präsentation von S2 mussten die Probanden signalisieren, ob die Lateralisierungswinkel der beiden Stimuli übereinstimmten oder nicht. Die Signale der einzelnen Sensoren wurden mit einem statistischen Wahrscheinlichkeitsmapping untersucht. Dabei wollten wir Unterschiede in der spektralen Amplitude für Stimuli mit 15° bzw. 45° Lateralisierungswinkel identifizieren. Wir konnten spezifische Gamma-Aktivität für alle Beispielstimuli nachweisen. Die Signale wurden im Bereich von 59-72 Hz gefunden und waren über dem parieto-okzipitalen Kortex jeweils kontralateral zur stimulierten Seite lokalisiert. Die maximalen Spektralamplituden dieser Oszillationen traten während der mittleren 200-300 ms der Verzögerungsphase auf und nahmen zu ihrem Ende hin ab. Zusätzlich haben wir Korrelationen zwischen der Aktivierungsstärke der Gamma-Komponenten und dem Abschneiden bei der Gedächtnisaufgabe untersucht. Dabei zeigte sich, dass der Unterschied der oszillatorischen Antworten auf bevorzugte und nicht-bevorzugte Stimuli während der letzten 100 ms der Verzögerungsphase positiv mit der Leistung in der Gedächtnisaufgabe korrelierte. Diese Ergebnisse sprechen dafür, dass die beobachteten Gamma Komponenten die Aktivität neuronaler Netzwerke, die auf die Verarbeitung räumlicher auditorischer Information spezialisiert sind, widerspiegeln. Die Aktivierung dieser Netzwerke scheint zur Aufrechterhaltung aufgabenbezogener Information im Kurzzeitgedächtnis beizutragen

Development of Pharmacological Magnetic Resonance Imaging Methods and their Application to the Investigation of Antipsychotic Drugs: a Dissertation

Pharmacological magnetic resonance imaging (phMRI) is the use of functional MRI techniques to elucidate the effects that psychotropic drugs have on neural activity within the brain; it is an emerging field of research that holds great potential for the investigation of drugs that act on the central nervous system by revealing the changes in neural activity that mediate observable changes in behavior, cognition, and perception. However, the realization of this potential is hampered by several unanswered questions: Are the MRI measurements reliable surrogates of changing neural activity in the presence of pharmacological agents? Is it relevant to investigate psychiatric phenomena such as reward or anxiolysis in anesthetized, rather than conscious animals? What are the methods that yield reproducible and meaningful results from phMRI experiments, and are they consistent in the investigations of different drugs? The research presented herein addresses many of these questions with the specific aims of 1) Developing pharmacological MRI methodologies that can be used in the conscious animal, 2) Validating these methodologies with the investigation of a non-stimulant, psychoactive compound, and 3) Applying these methodologies to the investigation of typical and atypical antipsychotic drugs, classes of compounds with unknown mechanisms of therapeutic action Building on recent developments in the field of functional MRI research, we developed new techniques that enable the investigator to measure localized changes in metabolism commensurate with changing neural activity. We tested the hypothesis that metabolic changes are a more reliable surrogate of changes in neural activity in response to a cocaine challenge, than changes observed in the blood-oxygen-level-dependent (BOLD) signal alone. We developed a system capable of multi-modal imaging in the conscious rat, and we tested the hypothesis that the conscious brain exhibits a markedly different response to systemic morphine challenge than the anesthetized brain. We identified and elucidated several fundamental limitations of the imaging and analysis protocols used in phMRI investigations, and developed new tools that enable the investigator to avoid common pitfalls. Finally, we applied these phMRI techniques to the investigation of neuroleptic compounds by asking the question: does treatment with typical or atypical antipsychotic drugs modulate the systems in the brain which are direct or indirect (i.e. downstream) substrates for a dopaminergic agonist? The execution of this research has generated several new tools for the neuroscience and drug discovery communities that can be used in neuropsychiatric investigations into the action of psychotropic drugs, while the results of this research provide evidence that supports several answers to the questions that currently limit the utility of phMRI investigations. Specifically, we observed that metabolic change can be measured to resolve discrepancies between anomalous BOLD signal changes and underlying changes in neural activity in the case of systemically administered cocaine. We found clear differences in the response to systemically administered morphine between conscious and anesthetized rats, and observed that only conscious animals exhibit a phMRI response that can be explained by the pharmacodynamics of morphine and corroborated by behavioral observations. We identified fundamental and drug-dependent limitations in the protocols used to perform phMRI investigations, and designed tools and alternate methods to facilitate protocol development. By applying these techniques to the investigation of neuroleptic compounds, we have gained a new perspective of the alterations in dopaminergic signaling induced by treatment with antipsychotic medications, and have found effects in many nuclei outside of the pathways that act as direct substrates for dopamine. A clearer picture of how neuroleptics alter the intercommunication of brain nuclei would be an invaluable resource for the classification of investigational antipsychotic drugs, and would provide the basis for future studies that examine the neuroplastic changes that confer therapeutic efficacy following chronic treatment with antipsychotic medications

Development of a magnetic resonance compatible wrist device for the analysis of movement encoding in the brain

Tese de mestrado integrado em Engenharia Biomédica e Biofísica, apresentada à Universidade de Lisboa, através da Faculdade de Ciências, 2016A interação com o mundo é feita através de movimento - desde a locomoção até à comunicação verbal - tornando o controlo de movimento um dos aspectos fundamentais de maior interesse em neurociência. O controlo de movimento tem sido alvo de observação desde cedo em estudos comportamentais e neurofisiológicos, e sabemos hoje que os movimentos voluntários resultam de padrões de impulsos elétricos gerados no sistema nervoso. Contudo, não conhecemos ainda os aspetos mais precisos da geração de padrões de movimento nem a sua relação com parâmetros como direção, velocidade, etc. Uma característica importante do controlo de movimento é a existência de tuning direcional - que consiste numa resposta neuronal preferencial a uma direção de movimento. Ao executar movimentos numa direção preferida, alguns neurónios despolarizam a uma frequência máxima, e a mesma diminui gradualmente à medida que o movimento se afasta da direção preferida. Este fenómeno foi caracterizado em 1982 em áreas motoras (córtex motor primário) ao serem executados movimentos direcionais do braço contralateral. Contudo, estudos recentes mostram a existência de tuning direcional não só para o membro contralateral, mas também para o membro ipsilateral. Estas representações direcionais foram encontradas com medições electrofisiológicas ao nível celular, e também com técnicas modernas de imagiologia que medem sinal proveniente de volumes da ordem de mm3, como ressonância magnética funcional. Com recurso a ambos os tipos de técnicas foram encontradas representações ipsilaterais bem estruturadas para movimentos ao nível do braço bem como dos dedos. Desta forma, ambos os hemisférios cerebrais codificam movimentos direccionais de ambas as mãos. Sabemos também, por experiência quotidiana, que os movimentos bimanuais são bem coordenados, o que sugere que os mesmos são gerados tomando em conta informação de ambas as mãos. No entanto, a relação entre os padrões neuronais de movimentos bimanuais e unimanuais ainda não é clara. Nesta dissertação pretende-se localizar e caracterizar tuning direcional durante movimentos unimanuais e bimanuais no cérebro humano. Desta forma temos como objectivo procurar quais as regiões corticais que codificam movimentos direcionais da mão contralateral, da mão ipsilateral, bem como as representações de movimentos bimanuais e a sua relação com movimentos unimanuais. Para tal, foi desenhada uma experiência motora para testar movimentos direcionais, que foi executada em simultâneo com a aquisição de imagens de ressonância magnética funcional. Foi desenvolvido um dispositivo para monitorizar de forma precisa movimentos da mão. De forma a assegurar compatibilidade com o ambiente em ressonância magnética, foram construídos dois manípulos ergonómicos com recurso a impressão 3D em nylon. Os manípulos foram equipados com sensores de rotação resistivos, e foram montados numa mesa de suporte desenvolvida para o efeito. Afim de treinar os participantes e controlar a experiência, foi desenvolvido um protocolo motor organizado de forma semelhante a um jogo de alvos. Os participantes controlaram a posição de cursores num ecrã utilizando movimentos das mãos, monitorizados pelo dispositivo. O objectivo do protocolo motor foi atingir 6 alvos radiais com os cursores e voltar à posição central, com movimentos de cada uma das mãos, ou as duas (para todas as combinações de 6 alvos para cada mão). No total, a experiência consistiu em 48 condições de movimento – 6 movimentos radiais para a mão esquerda, 6 para a mão direita e 36 combinações bimanuais. A experiência motora foi executada por 7 sujeitos destros saudáveis. Após uma sessão de treino, a experiência decorreu num scanner de ressonância magnética funcional Siemens Trio 3T, onde foram adquiridas imagens funcionais durante 10 repetições da experiência para cada sujeito. Adicionalmente, foram adquiridos dados de cinemática para as duas mãos durante as sessões de treino e de teste. A análise de dados de cinemática consistiu na observação de tempos de reação e de movimento em cada condição. Comparámos condições unimanuais e bimanuais, testámos efeitos de direção, e ainda combinações bimanuais (movimentos simétricos, paralelos ou não relacionados). Para cada uma destas hipóteses foram usados os testes estatísticos aplicáveis. Não foram observados efeitos significativos nos tempos de reação, de forma consistente, para qualquer das condições em estudo. Pelo contrário, os tempos de movimento foram consistentemente sensíveis aos efeitos estudados. As imagens por ressonância magnética funcional foram analisadas numa primeira fase conforme o procedimento tradicional. Este consiste no pré-processamento - envolvendo correções espaciais de efeitos de campo magnético, filtragem temporal, alinhamento com a imagem anatómica e segmentação. De seguida foi aplicado um modelo linear de forma de forma de independente para cada voxel (unidade discreta de volume) nas imagens. O modelo consistiu em 48 variáveis categóricas, correspondentes às condições de movimento em estudo, e 10 variáveis categóricas correspondentes às sessões de repetição da experiência. O objetivo deste modelo é a estimação dos pesos (β) da regressão linear, i.e., para cada condição é estimada a influência da mesma no sinal em cada voxel. De seguida é possível fazer inferência sobre os valores β - sob a hipótese nula de que são, em média, zero. Procedendo desta forma, foi aplicado um teste t aos regressores β associados a movimentos da mão esquerda, direita, e movimentos bimanuais para as regiões: área sensorial somática I (S1), córtex motor primário (M1), córtex pré-motor ventral e dorsal (PMv, PMd), área motora suplementar (AMS), lóbulo parietal superior, anterior e posterior (LPSa, LPSp) e córtex visual (V12). Foram encontrados valores de activação predominantemente associados com movimentos contralaterais e bimanuais, e activação menor em movimentos ipsilaterais. Os resultados coincidem fortemente com a perspetiva clássica de que cada hemisfério está associado a controlo da mão contralateral. Contudo, os métodos univariados testam o quanto os voxels (ou regiões) variam a sua resposta com condições individuais, tornando a comparação entre condições de movimento difícil. Adicionalmente, estes métodos são indicados para o mapeamento de activação perante estímulos, mas não para avaliar a estrutura da representação de condições, i.e., caracterizar respostas neuronais associadas conjunto de estímulos - como é o caso de tuning direcional. Desta forma, foi aplicado um modelo de análise representacional no qual se pressupõe que os estímulos podem ser caracterizados por padrões de activação - neste caso correspondentes aos valores beta para cada voxel quando é executada uma condição. Neste modelo é calculada uma medida de (dis)similaridade entre todos os pares de condições. Neste projecto foi utilizada a distância Euclidiana, sendo que as comparações entre pares das 48 condições foram organizadas em matrizes de distância. Os resultados revelam, qualitativamente, a presença duma estrutura de tuning direcional bem definida para movimentos contralaterais, bem como ipsilaterais. Também os movimentos bimanuais apresentaram uma estrutura de tuning bem definida e diferenciada entre regiões. De forma a quantificar e inferir acerca da presença de codificação direcional, os valores de distância correspondentes às condições contralaterais, ipsilaterais e bimanuais foram testados estatisticamente. Este teste assenta no pressuposto de que, perante a inexistência de codificação, as distâncias são zero (este pressuposto foi confirmado). Os resultados indicam uma forte codificação direcional de movimentos contralaterais para todas as regiões testadas. Este resultado é coincidente com estudos anteriores que encontram tuning direcional contralateral em todas as regiões em que o mesmo foi investigado. Contudo, encontrámos também uma forte codificação de movimentos ipislaterais, excepto na AMS e LPS anterior no hemisfério direito (não dominante). Estes resultados são coerentes com estudos recentes que mostram uma forte presença de codificação de movimentos ipsilaterais. Os movimentos bimanuais estão também caracterizados por uma forte representação. Contudo, existe a hipótese de que estes estejam presentes apenas como consequência da codificação direcional de movimentos da mão contralateral (ou ipsilateral), e não directamente associados à codificação especializada de movimentos bimanuais. Esta hipótese é, contudo, de elevado interesse, já que uma codificação bimanual especializada pode explicar o mecanismo da coordenação bimanual. Desta forma, as matrizes de distância foram reorganizadas em termos de movimentos da mão esquerda e da mão direita. Os mapas resultantes foram comparados qualitativamente com simulações, revelando uma codificação bimanual maioritariamente associada com movimentos contralaterais. Contudo, a AMS e o córtex premotor ventral aparentam codificar movimentos bimanuais de forma não-linear, que poderá indicar alguma especialização em movimentos bimanuais que poderá ser útil para coordenação. Trabalho futuro envolverá avaliar quantitativamente estes mapas de forma a perceber quanta codificação bimanual é gerada de forma especializada. Os resultados deste estudo coincidem com estudos recentes de codificação ipsilateral, e revisitam questões acerca da codificação bimanual. No futuro pretende-se decompor a codificação bimanual, avaliar de forma extensa e continua a superfície cortical, cerebelo e núcleos da base. Adicionalmente, esperamos executar futuras aquisições em novos participantes. Este tipo de estudo pretende responder a questões no âmbito do controlo neural de movimento, que poderão ser úteis futuramente no contexto da reabilitação e controlo robótico. Consideramos também que os métodos de procura de codificação poderão ser utilizados para caracterização do sistema motor de sujeitos saudáveis em comparação com casos patológicos como acidente vascular cerebral, fornecendo um meio de avaliação dos mesmos.We interact with the world by moving our body: legs for locomotion, hands for dexterous tasks, and articulatory muscles to communicate. It is known that these movements result from patterns of electrical impulses in the nervous system. However, it is not yet known how the brain controls the fine aspects of movement. One important characteristic of movement control in the brain is directional tuning - a preferential neuronal response to an executed direction. In this work, we examine where and how the brain encodes movement directions in unimanual and bimanual movements in humans. In order to address this question, we designed a motor experiment for directional movements. A hand device was developed in order to precisely monitor hand movements while 7 right-handed healthy participants executed a motor task. The task was built similarly to a game in which participants reached radial targets using wrist movements of one or both hands. After training, subjects executed the motor task in a magnetic resonance scanner. Functional imaging data were acquired and analysed using novel multivoxel pattern analysis, in which we calculate pairwise dissimilarities of patterns of fMRI voxel activity across movement conditions. We tested for encoding of unimanual (contralateral and ipsilateral) and bimanual movements in cortical regions of interest. Kinematics data were also analysed to test for performance effects of direction and hand combination. We found significant encoding of contralateral and bimanual movements in all tested regions. Ipsilateral movements were strongly represented in both hemispheres, except for right supplementary motor area and anterior-superior parietal lobule. Furthermore, the right (non-dominant) hemisphere encoded contralateral movements more preferentially than ipsilateral ones, when compared with the left hemisphere. These results are in line with recent findings of well-defined ipsilateral movement representations. Future work will involve decomposing bimanual tuning functions in order to find a quantitative relationship between bimanual and unimanual encoding

Molecular Mechanisms Responsible for Functional Cortical Plasticity During Development and after Focal Ischemic Brain Injury

The cerebral cortex is organized into functional representations, or maps, defined by increased activity during specific tasks. In addition, the brain exhibits robust spontaneous activity with spatiotemporal organization that defines the brain’s functional architecture (termed functional connectivity). Task-evoked representations and functional connectivity demonstrate experience-dependent plasticity, and this plasticity may be important in neurological development and disease. An important case of this is in focal ischemic injury, which results in destruction of the involved representations and disruption of functional connectivity relationships. Behavioral recovery correlates with representation remapping and functional connectivity normalization, suggesting functional organization is critical for recovery and a potentially valuable therapeutic target. However, the cellular and molecular mechanisms that drive this systems-level plasticity are unknown, making it difficult to approach therapeutic modulation of functional brain organization. Using cortical neuroimaging in mice, this dissertation explores the role of specific genes in sensory deprivation induced functional brain map plasticity during development and after focal ischemic injury. In the three contained chapters, I demonstrate the following: 1) Arc, an excitatory neuron synaptic-plasticity gene, is required for representation remapping and behavioral recovery after focal cortical ischemia. Further, perilesional sensory deprivation can direct remapping and improve behavioral recovery. 2) Early visual experience modulates functional connectivity within and outside of the visual cortex through an Arc-dependent mechanism. 3) Electrically coupled inhibitory interneuron networks limit spontaneous activity syncrhony between distant cortical regions. This work starts to define the molecular basis for plasticity in functional brain organization and may help develop approaches for therapeutic modulation of functional brain organization

An investigation of factual and counterfactual feedback information in early visual cortex

Primary visual cortex receives approximately 90% of the input to the retina, however this only accounts for around 5% of the input to V1 (Muckli, 2010). The majority of the input to V1 is in fact from other cortical and sub-cortical parts of the brain that arrive there via lateral and feedback pathways. It is therefore critical to our knowledge of visual perception to understand how these feedback responses influence visual processing. The aim of this thesis is to investigate different sources of non-visual feedback to early visual cortex. To do this we use a combination of an occlusion paradigm, derived from F. W. Smith and Muckli (2010), and functional magnetic resonance imagining. Occlusion offers us a method to inhibit the feedforward flow of information to the retina from a specific part of the visual field. By inhibiting the feedforward information we exploit the highly precise retinotopic organisation of visual cortex by rendering a corresponding patch of cortex free of feedforward input. From this isolated patch of cortex we can ask questions about the information content of purely feedback information. In Chapter 3 we investigated whether or not information about valance was present in non-stimulated early visual cortex. We constructed a 900 image set that contained an equal number of images for neutral, positive and negative valance across animal, food and plant categories. We used an m-sequence design to allow us to present image set within a standard period of time for fMRI. We were concerned about low-level image properties being a potential confound, so a large image set would allow us to average out these low-level properties. We occluded the lower-right quadrant of each image and presented each image only once to our subjects. The image set was rated for valance and arousal after fMRI so that individual subjectivity could be accounted for. We used multivariate pattern analysis (MVPA) to decode pairs of neutral, positive and negative valance. We found that in both stimulated and non-stimulated V1, V2 and V3, and the amygdala and pulvinar only information about negative valance could be decoded. In a second analysis we again used MVPA to cross-decode between pairs of valance and category. By training the classifier on pairs of valance that each contained two categories, we could ask the question of whether the classifier generalises to the left out category for the same pair of valance. We found that valance does generalise across category in both stimulated and non-stimulated cortex, and in the amygdala and pulvinar. These results demonstrate that information about valance, particularly negative valance, is represented in low level visual areas and is generalisable across animal, food and plant categories. In Chapter 4 we explored the retinotopic organisation of object and scene sound responses in non-stimulated early visual cortex. We embedded a repeating object sound (axe chopping or motor starting) in to a scene sound (blizzard wind or forest) and used MVPA to read out object or scene information from non-stimulated early visual cortex. We found that object sounds were decodable in the fovea and scene sounds were decodable in the periphery. This finding demonstrates that auditory feedback to visual cortex has an eccentricity bias corresponding to the functional role involved. We suggest that object information feeds back to the fovea for fine-scaled discrimination whereas abstract information feeds back to the periphery to provide a modulatory contextual template for vision. In a second experiment in Chapter 4 we further explored the similarity between categorical representations between sound and video stimuli in non-stimulated early visual cortex. We use video stimuli and separate the audio and visual parts in to unimodal stimuli. We occlude the bottom right quadrant of the videos and use MVPA to cross-decode between sounds and videos (and vice-versa) from responses in occluded cortex. We find that a classifier trained on one modality can decode the other in occluded cortex. This finding tells us that there is an overlap in the neural representation of aural and visual stimuli in early visual cortex. In Chapter 5 we probe the internal thought processes of subjects after occluding a short video sequence. We use a priming sequence to generate predictions as subjects are asked to imagine how events from a video unfold during occlusion. We then probe these predictions with a series of test frames corresponding to points in time, either close in time to the offset of the video, just before the video would be expected to reappear, the matching frame from when the video would be expected to reappear or a frame from the very distant future. In an adaption paradigm we find that predictions best match the test frames around the point in time that subjects expect the video to reappear. The test frame from a point close in time to the offset of the video was rarely a match. This tells us that the predictions that subjects make are not related to the offset of the priming sequence but represent a future state of the world that they have not seen. In a second control experiment we show that these predictions are absent when the priming sequence is randomised, and that predictions take between 600ms and 1200ms to fully develop. These findings demonstrate the dynamic flexibility of internal models, that information about these predictions can be read out in early visual cortex and that stronger representations form if given additional time. In Chapter 6 we again probe at internal dynamic predictions by using virtual navigation paradigm. We use virtual reality to train subjects in a new environment where they can build strong representations of four categorical rooms (kitchen, bedroom, office and game room). Later in fMRI we provide subjects with a direction cue and a starting room and ask them to predict the upcoming room by combining the information. The starting room is shown as a short video clip with the bottom right quadrant occluded. During the video sequence of the starting room, we find that we can read out information about the future room from non-stimulated early visual cortex. In a second control experiment, when we remove the direction cue information about the future room can no longer be decoded. This finding demonstrates that dynamic predictions about the immediate future are present in early visual cortex during simultaneous visual stimulation and that we can read out these predictions with 3T fMRI. These findings increase our knowledge about the types of non-visual information available to early visual cortical areas and provide insight in to the influence they have on vision. These results lend support to the idea that early visual areas may act as a blackboard for read and write operations for communication around the brain (Muckli et al., 2015; Mumford, 1991; Murray et al., 2016; Roelfsema & de Lange, 2016; Williams et al., 2008). Current models of predictive coding will need to be updated to account for the brains ability to switch between two different processing streams, one that is factual and related to an external stimulus and one that is stimulus independent and internal