The human cortical temporoparietal junction (TPJ) has been implicated in cognitive processes including attentional reorienting, social cognition, and behavioral inhibition. Functional organization of TPJ remains unclear due to individual differences in anatomy. This dissertation describes functional magnetic resonance imaging (fMRI) experiments examining TPJ at the level of individuals. A method to localize TPJ using fMRI in individual subjects was developed and tested. TPJ subregions for social cognition, behavioral inhibition, and attention reorienting were parcellated. Finally, differences in attention networks between practitioners of focused attention meditation and matched control participants were investigated. Fifty individuals (ages 20-58; 21 women) participated. Experiment 1 (n=10) developed and tested a novel fMRI paradigm ('CueBall') that combined two forms of attentional reorienting; participants directed and shifted attention in a spatial cueing task and were distracted by the infrequent and unexpected presentation of task-irrelevant images ('oddballs'). The contrast of 'oddball distractor' to 'non-oddball' trials robustly identified TPJ in individual brains. Bilateral subdivisions of TPJ were identified in the fundus of the superior temporal sulcus (STS) and in ventral supramarginal gyrus (SMG). Experiment 2 (n=10, including one individual from Experiment 1) employed the CueBall task along with a Stop Signal task and a Theory of Mind task to determine whether these disparate tasks recruit common or distinct cortical areas. The data demonstrated functional overlap in anterior TPJ between the attention and behavioral inhibition tasks and in posterior TPJ for attention and Theory of Mind. Experiment 3 (n=30) investigated neural correlates of focused attention meditation training in the dorsal attention network (DAN), the default mode network (DMN), and ventral attention network (VAN). Meditators demonstrated an increased magnitude of differential activation in DAN vs. DMN in a sustained attention task, relative to matched controls. In contrast, attentional reorienting did not reveal attention network differences between meditators and controls. Taken together, this work validates an attentional fMRI tool, helps disambiguate functional organization of the TPJ, and demonstrates neural correlates of improved attention in humans with meditation experience. / 2020-03-31T00:00:00Z

Given the difficulty in predicting outcomes in persons with stroke-induced aphasia (PWA), neuroimaging-based biomarkers of recovery could provide invaluable predictive power to stroke models. However, the neural patterns that constitute beneficial neural organization of language in PWA remain debated. Thus, in this work, we propose a novel network theory of aphasia recovery and test our overarching hypothesis, i.e., that task-specific language processing in PWA requires the dynamic engagement of intact tissue within a bilateral network of anatomically-segregated but functionally and structurally connected language-specific and domain-general brain regions. We first present two studies in which we examined left frontotemporal connectivity during different language tasks (i.e., picture naming and semantic feature verification). Results suggest that PWA heavily rely on left middle frontal gyrus (LMFG)-driven connectivity for tasks requiring lexical-semantic processing and semantic control whereas controls prefer models with input to either LMFG or left inferior frontal gyrus (LIFG). Both studies also revealed several significant associations between spared tissue, connectivity and language skills in PWA. In the third study, we examined bilateral frontotemporoparietal connectivity and tested a lesion- and connectivity-based hierarchical model of chronic aphasia recovery. Between-group comparisons showed controls exhibited stronger left intra-hemispheric task-modulated connectivity than did PWA. Connectivity and language deficit patterns most closely matched predictions for patients with primarily anterior damage whereas connectivity results for patients with other lesion types were best explained by the nature of the semantic task. In the last study, we investigated the utility of lesion classification based on gray matter (GM) only versus combined GM plus white matter (WM) metrics. Results suggest GM only classification was sufficient for characterizing aphasia and anomia severity but the GM+WM classification better predicted naming treatment outcomes. We also found that fractional anisotropy of left WM association tracts predicted baseline naming and treatment outcomes independent of total lesion volume. Finally, results of a preliminary multimodal prediction analysis suggest that combined structural and functional metrics reflecting the integrity of regions and connections comprise optimal predictive models of behavior in PWA. To conclude this dissertation, we discuss how multimodal network models of aphasia recovery can guide future investigations. / 2020-10-23T00:00:00Z

Recent functional neuroimaging research has highlighted the role of the posterior parietal cortex (PPC) during episodic memory retrieval (Vilberg & Rugg, 2007; Vincent et al., 2006; Wagner et al., 2005; Wheeler & Buckner, 2003; Yonelinas et al., 2005). It has been shown that the PPC is active during the retrieval of old information, when subjects incorrectly believe that new information has been encountered before (false alarms), and when retrieval is accompanied by recollection (Wagner et al., 2005). A preliminary positron emission tomography (PET) study suggests that the PPC is also active when retrieval occurs unintentionally or incidentally, prompted by the presence of an old stimulus item. Collectively these studies suggest that activity in the PPC may be driven by familiarity, irrespective of task demands and independent of its veracity. The main goal of this thesis was to explore, with functional magnetic resonance imaging (fMRI), the conditions under which activity in the PPC may be modulated by the familiarity of veridical and perceived memories. Subjects were presented with scene/word pairs that were repeated 1, 3, or 7 times on Day 1. On Day 2, while MRI scans were recorded, subjects studied either, new items, old pairs (same-form) one additional time (2nd,, 4th, or 8th presentation), or pairs in which the word associated with each picture was changed (different-form) one additional time (2nd,, 4th, or 8th presentation). Same form pairs activated bilateral inferior parietal lobule compared to novel pairs replicating the findings from the PET study on incidental retrieval. Same and different form pairs did not differ on amount of parietal activity. Additionally, same form pairs that were repeated 8 times displayed more PPC activity than same form pairs repeated two and four times while there was no difference across different form repetitions. Together these results indicate that items that are old and that those that are new but are perceived as old activate the inferior parietal lobule.

No neuroimaging investigation to date has considered the effects of social context on self-referential processing, despite the fact that the hypothesis that people engage different selves in different contexts has been with psychology for more than a century. To address this gap in the empirical record, a suite of three functional magnetic resonance imaging (fMRI) experiments was conducted in order to assess patterns of neural activity associated with self-referential (compared to non-self-referential) processes (Experiment 1), computational models of reinforcement-learning processes (Experiment 2), and social context modulation of personally relevant cognition (Experiment 3). I demonstrate that distinct patterns of neural activity in cortical midline structures and the mesial ventral striatum are associated with thinking about the self privately, sharing information about the self with a parent, and sharing with a friend. These differentiated disclosure responses (Experiment 3) are evident at the whole brain level and in regions of interest defined by functional activity in independent tasks of self (Experiment 1) and reward (Experiment 2). In addition to providing empirical evidence for contextually differentiated self-representations in the brain, this dissertation validates the use of fMRI paradigms designed to functionally localize self-referential and reward-related activity either independently or in conjunction, as well as distinguish components of ventral striatal activity unique to each task. Finally, I consider strategies for approaching future investigations of self and social cognition in terms of reinforcement learning.

Despite a central role for morphological knowledge in supporting linguistic generalisation, the neural representations supporting its learning remain largely unexplored. This thesis addressed this gap by exploring the role of memory consolidation in morphological learning and generalisation. In three experiments, adult participants learned an artificial language in which stems (e.g. gleet, shiln) combined with plural affixes (e.g. –aff, -opp; gleetaff, shilnopp) to refer to the occupation of multiple male and female characters. Mimicking properties of morphological systems in natural languages, the plurals varied in their phonological consistency/ambiguity and type/token frequency. Two sets of plurals, distinguished by gender, were trained on two successive days. Experiment 1 revealed that generalisation to novel phonologically ambiguous forms measured on the second day showed a greater influence of token frequency for plurals trained on the previous day, suggesting overnight changes in their underlying representations. Experiment 2 examined this effect further by using fMRI to compare the neural representations underlying plurals learned on the day of scanning or on the previous day. Representational Similarity Analysis revealed increased similarity structure among high type frequency plurals and reduced similarity structure among high token frequency plurals following overnight consolidation in the left superior temporal gyrus (STG). These results are consistent with a Complementary Learning Systems (CLS) model in which overnight consolidation supports the development of overlapping representations among several items sharing the same feature (here, an affix; type frequency) and strengthens item-specific representations for frequently occurring items (token frequency). Additionally, connectivity analyses showed that the functional coupling between the left STG and the left dorsolateral prefrontal cortex was weaker for high type frequency plurals and stronger for high token frequency plurals following overnight consolidation. These results suggest that the engagement of prefrontal control processes in retrieving the newly-learned plurals is subject to overnight consolidation and sensitive to the similarity structure underlying the plurals to be retrieved. However, the overnight changes in similarity structure and functional networks observed in Experiment 2 were not mirrored by changes in generalisation to novel forms as were observed in Experiment 1. Experiment 3 aimed to address the discrepancy in consolidation-related changes in generalisation behaviour between the first two experiments. Type/token frequencies were manipulated to bias learning, consolidation, and generalisation towards high token frequency plurals. Despite this manipulation, no consolidation-related changes in generalisation were observed. Findings from all three experiments are interpreted in the context of the CLS model and a role for overnight consolidation in morphological learning and generalisation is discussed.

O mapeamento das respostas BOLD (Blood Oxygenation Level Dependent) constitui etapa importante nos experimentos de imagem funcional por ressonância magnética (Functional Magnetic Resonance Imaging fMRI) e de EEG-fMRI simultâneo. Em sua grande maioria, a análise de dados de fMRI e de EEG-fMRI está baseada no modelo linear geral (General Linear Model GLM), que procura localizar as respostas BOLD por meio de modelos definidos a priori. Porém, em muitos casos, como em pacientes, variações na forma e/ou atraso podem reduzir a confiabilidade dos resultados. Desse modo, o primeiro objetivo deste trabalho foi explorar métodos clássicos e propor novos métodos para análise de dados de fMRI e de EEG-fMRI simultâneo. Neste trabalho, um método modificado baseado na distância de Kullback-Leibler generalizada (dKLg) foi desenvolvido. Diferentemente do GLM, essa abordagem não requer um modelo para a resposta. Dados simulados foram utilizados para otimizá-lo e compará-lo ao GLM sob diferentes condições de resposta como a relação sinal ruído e a latência. Em seguida, o dKLg foi testado em dados reais, adquiridos em 14 voluntários assintomáticos, submetidos a tarefas motoras e auditivas padrões. Os resultados mostram a equivalência entre o dKLg e o GLM. Em seguida, essa estratégia foi testada em 02 pacientes com com estenose carotídea unilateral. Neste caso, o dKLg foi capaz de detectar regiões significativas ipsilaterais à estenose, não detectadas pelo GLM, em virtude do atraso do sinal BOLD. Em seguida, esses métodos foram aplicados sobre exames de EEG-fMRI realizados em 45 pacientes com epilepsia. Para esse conjunto de dados, mais uma abordagem foi elaborada, que utiliza a Análise de Componentes Independentes (Independent Component Analysis ICA). Denominado ICA-GLM, ele permite extrair de modo semi-automático a amplitude, duração e topografia das descargas epileptiformes interictais (Interictal Epileptiform Discharges IED), favorecendo a inclusão de sinais do EEG de menor destaque. Além dessa vantagem, ele ainda permite incluir modelos do sinal BOLD com diferentes latências, aumentando a abrangência da variabilidade das respostas encontradas em pacientes com epilepsia. A eficiência do ICA-GLM também foi comparado à do GLM e dKLg nos exames de EEG-fMRI. Embora os resultados tenham demonstrado a robustez do GLM, em alguns pacientes o dKLg foi mais eficiente para localizar regiões concordantes que não foram detectadas pelo GLM. Ainda, em boa parte dos casos o ICA-GLM detectou regiões mais extensas e com maior valor estatístico, quando comparado ao GLM. De forma geral, nota-se que o dKLg e ICA-GLM podem ser ferramentas complementares importantes ao GLM, aumentando a sensibilidade dos exames de EEG-fMRI como um todo. Outra etapa importante nas avaliações de EEG-fMRI em pacientes com epilepsia tem sido a utilização de imagens de fontes elétricas (Electrical Source Imaging ESI). Neste trabalho, os mapas de ESI foram obtidos por dois métodos de solução inversa distribuída nunca usados no cenários da EEG-fMRI: Bayesian Model Averaging (BMA) e constrained Low Resolution Electromagnetic Tomography (cLORETA). Além da construção dos mapas de ESI, avaliamos a utilidade de combinar as técnicas de ESI e de EEG-fMRI para promover a diferenciação entre fontes primárias e de propagação temporal. Essa análise permitiu avaliar a concordância entre as regiões detectadas pelo ESI e EEG-fMRI e diferenciar as respostas BOLD relacionadas aos componentes iniciais e posteriores da IED. Embora os resultados ainda sejam preliminares para eleger qual método seria mais eficiente (cLORETA ou BMA), a distância encontrada entre o máximo ESI e o cluster de EEG-fMRI mais próximo foi consistentemente similar, em ambos, com os dados recentes da literatura. / Functional magnetic resonance imaging (fMRI) and combined EEG-fMRI usually rely on the successful detection of Blood Oxygenation Level Dependent (BOLD) signal. Typically, the analysis of both fMRI and EEG-fMRI are based on the General Linear Model (GLM) that aims at localizing the BOLD responses associated to an a priori model. However, the responses are not always canonical, as is the case of those from patients, which may reduce the reliability of the results. Therefore, the first objective of the present study was to explore the usage of classical methods, such as the GLM, and to propose alternative strategies to the analysis of fMRI and combined EEG-fMRI. A first method developed was based on the computation of the generalized Kullback-Leibler distance (gKLd), which does not require the use of an a priori model. Simulated data was used to allow quantitative comparison between the gKLd and GLM under different response conditions such as the signal to noise ratio and delay. The gKLd was then tested on real data, first from 14 asymptomatic subjects, submitted to classical motor and auditory fMRI protocols. The results demonstrate that under these conditions the GLM and gKLd are equivalent. The same strategy was applied to 02 patients with unilateral carotid stenosis. Now the dKLg was capable of detecting the expected bilateral BOLD responses that were not detected by the GLM, as a consequence of the response delay imposed by the stenosis. Those comparisons were now extended to the evaluation of EEG-fMRI exams from 45 patients with epilepsy. For this data set, an additional method was used, based on the use of Independent Component Analysis (ICA), which was called ICA-GLM. It allows extracting semi-automatically the amplitude, duration and topography of EEG interictal Epileptiform Discharges (IED), favoring the use of less prominent signals. Moreover, it also allows the use of BOLD response models with different delays, expanding the variability of the responses to be detected in patients with epilepsy. ICA-GLM was also compared to GLM and dKLg in these EEG-fMRI evaluations. Although in general the results have demonstrated the robustness of the GLM, dKLg was more efficient in detecting the responses from some pacients, while the ICA-GLM mostly detected broader regions with more significant results when compared to GLM. In general, dKLg and ICA-GLM seem to offer an important complementary aspect to the GLM, increasing its sensibility in EEG-fMRI as a whole. Another important aspect of EEG-fMRI applied to patients with epilepsy has been the inspection of Electrical Source Imaging (ESI) to evaluate some dynamical aspects of the IED. Herein, ESI maps were obtained from two inverse distributed solutions that were not applied so far to EEG-fMRI: Bayesian Model Averaging (BMA) and constrained Low Resolution Electromagnetic Tomography (cLORETA). Besides, we also evaluated the combined information from ESI and EEG-fMRI in order to differentiate from primary sources to temporal propagation of the signal. Such analysis allowed us to inspect for the correspondence between regions detected by ESI e EEG-fMRI and to separate BOLD signals whose sources are related to the initial and later components of the IED. Although the results are preliminary to determine which ESI method (cLORETA or BMA) is more efficient, the distance between the maximum ESI and the closest EEG-fMRI cluster was consistently similar with those reported in the literature.

Muito embora a eletroencefalografia continue sendo amplamente empregada no estudo e diagnóstico da epilepsia, as imagens funcionais de ressonância magnética tornaram-se uma das principais ferramentas de acesso não invasivo às funções normais do cérebro. Atualmente, é uma realidade clínica a aplicação dessas técnicas para o mapeamento pré-cirúrgico e também nos estudos básicos em neurociência. Entretanto, em muitos casos é necessário um estudo combinado dessas duas técnicas. De um modo geral os sinais obtidos em experimentos de ressonância magnética funcional (fMRI) devem ser processados a fim de revelar o mapa de ativação, relativo ao estímulo aplicado. Entretanto até a presente data não há um método consensual para a análise dos sinais de fMRI. Nesse sentido, apresentamos nesse trabalho dois novos métodos para a análise de sinais de fMRI baseados em conceitos de teoria de informação utilizando a entropia de Tsallis. O primeiro método consiste em uma alternativa para análise de fMRI obtida através de paradigmas evento-relacionados, sem que a forma da resposta ao estímulo seja levada em conta. Utilizando a teoria de informação, consideramos a evolução temporal da entropia do sinal sem realizar nenhuma hipótese sobre a forma da função de resposta. O método se mostrou capaz de discriminar regiões ativas e não ativas em paradigmas motores e visuais. Através de simulações, observamos que o nosso método se apresenta mais estável com o o aumento do ruído quando comparado com o método clássico. O segundo método que desenvolvemos para análise de dados de fMRI (paradigmas em bloco) baseia-se no conceito de informação mútua generalizada (GMI). Neste sentido, obtivemos um amplo espectro de resultados dependentes do parâmetro q de Tsallis. Assim, realizaram-se análises em dados simulados de modo a construir as curvas características de um sistema receptor (curvas ROC). Determinando os parâmetros que avaliam a qualidade das curvas otimizamos os valores de q . Tanto os resultado obtidos das simulações quanto os obtidos através de imageamento em voluntários forma analisados comparando-se os métodos clássicos com o GMI. Outrossim, a determinação do foco epileptogênico é de grande interesse no diagnóstico e profilaxia da epilepsia. Essa determinação envolve muitas vezes a detecção da atividade anormal que ocorre entre as crises (atividades interictais). Esta tarefa demanda muito tempo dos neurofisiologistas por ser realizada através de inspeção visual. Os eventos anormais mais comumente observados apresentam duas componentes, uma de alta freqüência (ponta) e outra de mais baixa (onda). Assim sendo, desenvolvemos um algoritmo que se utiliza do conceito de multiresolução para detecção automática das atividades anormais e localização aproximada do foco epileptogênico. Como resultado, a localização do foco obtida através do algoritmo coincidiu com a indicada pelo neurofisiologista através da metodologia usual. As duas técnicas EEG e fMRI juntamente com os métodos propostos constituem o primeiro passo para um sistema de auxílio diagnóstico e planejamento cirúrgico.

A epilepsia do lobo temporal (ELT) é a forma mais comum de epilepsia e a mais resistente ao tratamento medicamentoso. Existem diversos tipos de drogas anti-epilépticas usadas no controle das crises. Entretanto, em alguns casos, esse tipo de tratamento não é eficaz e a cirurgia para remoção da zona epileptogênica (ZE) pode ser uma alternativa recomendada. A ZE é definida como aquela onde as crises são originadas. Trata-se de um conceito teórico e, atualmente, não existem técnicas capazes de delimitá-la precisamente. Na prática, exames de EEG, vídeo-EEG, MEG, SPECT, PET e diversas técnicas de MRI, em especial as funcionais, têm sido usados para mapear zonas relacionadas à ZE. Contudo, em alguns casos, os resultados permanecem não convergentes e a determinação da ZE inconclusiva. Desse modo, é evidente a importância do surgimento de novas metodologias para auxiliar a localização da ZE. Assim, pois, o objetivo deste trabalho foi desenvolver dois métodos para a avaliação da ZE, ambos baseados na imagem funcional por ressonância magnética. No primeiro, investigamos possíveis alterações da resposta hemodinâmica (HRF) quando da modulação da pressão parcial de CO2. Para tanto, fizemos um estudo sobre 22 pacientes com ELT e 10 voluntários assintomáticos modulando a pressão parcial de CO2 sanguíneo cerebral por um protocolo de manobra de pausa respiratória e outro de inalação passiva de CO2/ar. Os resultados mostram que o tempo de onset da HRF tende a ser maior e a amplitude da HRF tende a ser menor em áreas do lobo temporal de pacientes com ELT quando comparados com os dados de voluntários assintomáticos. Além disso, os resultados mostram mapas de onset individuais coincidentes com exames de SPECT ictal. O segundo estudo foi baseado em medidas de EEG-fMRI simultâneo. Neste, avaliamos a relação entres as potências dos ritmos cerebrais alfa e teta (EEG) e o contraste BOLD (fMRI) de 41 pacientes com ELT e 7 voluntários assintomáticos em estado de repouso. A análise da banda alfa mostrou correlações negativas nos lobos occipital, parietal e frontal tanto nos voluntários quanto nos pacientes com ELT. As correlações positivas nos voluntários foram dispersas e variáveis em ambos hemisférios cerebrais. Por outro lado, encontramos forte correlação positiva no tálamo e ínsula dos pacientes com ELT. Na análise da banda teta observamos correlações positivas bilaterais nos giros pré e pós central de voluntários. Ainda, foram observados clusters no cíngulo anterior, tálamo, ínsula, putamen, em regiões parietais superior, frontais e giros temporais. Também, utilizamos um cálculo de índice de lateralização (IL) no lobo temporal em confrontos entre pacientes com ELT à direita, pacientes com ELT à esquerda e voluntários assintomáticos. Verificamos que os ILs, utilizando os clusters obtidos nas análises em teta, foram coincidentes com o diagnóstico clínico prévio da localização da ZE em todas as análises dos grupos de pacientes com ELT à direita, e na maioria do grupo de pacientes com ELT à esquerda. De forma geral, verificamos que o método de hipercapnia se mostrou ferramenta interessante na localização da ZE comprovada pelos coincidentes achados pela avaliação de SPECT. Inferimos que o maior tempo de onset e menor amplitude da HRF observadas nos pacientes em relação a voluntários possam estar relacionados a um stress vascular devido à recorrência de crises. Já o método de ritmicidade alfa e teta proposto parece promissor para ser usado na determinação da lateralização da ZE em pacientes com ELT. / Temporal lobe epilepsy (TLE) is the most common and resistant form of epilepsy to anti-epileptic drug. There are several types of anti-epileptic drugs used in seizure control. However, in some cases drug treatment is not effective and surgery to remove the epileptogenic zone (EZ) is a recommended alternative. EZ is a theoretical concept and there are many techniques that have been applied to enclose it precisely. In practice, EEG, video-EEG, MEG, SPECT, PET and various MRI techniques, especially functional MRI (fMRI), have been used to map areas related to EZ. However, in some cases, the results remain non-convergent and the EZ, undefined. Therefore, the use of new methodologies to assist the location of EZ have been proposed. Herein, our goal was to develop two methods for assessing the EZ. The first one was designed to access changes in the hemodynamic response (HRF) of the EZ in response to hypercapnia. 22 patients with TLE and 10 normal volunteers were evaluated by modulating the partial pressure of CO2 during the acquisition of fMRI in a breathing holding and a passive inhalation CO2/air protocols. The results show increased onset times and decreased amplitude of the HRF in the temporal lobe of TLE patients compared with asymptomatic volunteers. Moreover, most patients had onset maps coincident with ictal SPECT localizations. The second proposed study was based on simultaneous EEG-fMRI acquisitions. The relationship between powers of alpha and theta bands (EEG) and BOLD contrast (fMRI) was investigated in 41 TLE patients and 7 healthy controls. Alpha band results show a consistent negative correlation in the occipital, parietal and frontal lobes both in controls and TLE patients. In addition, controls show disperse positive correlations in both hemispheres. On the other hand, TLE patients presented strong positive correlations in the thalamus and insula. Theta band analysis, in controls, primarily show positive correlations in bilateral pre-and post-central gyri. In patients, robust positive correlations were observed in the anterior cingulate gyrus, thalamus, insula, putamen, superior parietal, frontal and temporal gyri. Moreover, the lateralization index (LI) indicates a coincidence between the side of the EZ evaluated by clinical diagnosis and clusters detected in the theta band. In conclusion, the hipercapnia study showed to be an interesting tool in locating EZ and the results are similar to SPECT findings. The longer onset and lower amplitude of the HRF observed in patients may be related to a vascular stress due to the recurrence of seizures. Furthermore, alpha and theta rhythms may be a promising tool to be used in determining the lateralization of EZ in patients with TLE.

Memory updating has been established; however, the mechanism supporting this alteration process is subject to disagreement. Reconsolidation theorists argue that memory updating occurs via an old memory becoming reactivated and returned to a state of susceptibility. In this state, newly presented details can become incorporated into the existing memory. As such, memory updating is an effect of old memory reactivation and new information encoding. In contrast, temporal context theory argues that the temporal context in which the old memory was initially formed is reinstated. Newly presented information becomes tagged to the old context. Therefore, at retrieval, when the old context is reinstated again, the initially bound information and the newer information are simultaneously retrieved. Within this theoretical framework, memory modification is the result of retrieval effects. In contrast, this three-paper dissertation provides evidence that reconsolidation is, at least in part, a combined reactivation and encoding effect. In paper 1, I present neural evidence of both old memory reactivation and new encoding, which demonstrates 1) that strength at reactivation predicts the likelihood that a memory will be modified and 2) that greater brain activation during new encoding predicts the extent of accurate recognition. In paper 2, I show that encoding conditions affect the extent to which new information will be misattributed to the old memory. I demonstrate that learners update explicitly encoded memories but not implicitly coded ones. Lastly, in paper 3, I demonstrate that old memories can be reactivated and altered during sleep. When old-memory reactivation is paired with a forget cue, a subsequent degeneration of the memory and its details ensues. In sum, all three papers provide evidence in support of the reconsolidation theory that memory updating occurs during old-memory reactivation and new encoding.

Damage to motor areas of the brain, caused by stroke, can produce devastating motor deficits, including aberrant control of force. After stroke, reorganization of the brain’s motor system has been identified as one of the fundamental mechanisms involved in recovery of motor control after stroke. Yet, few studies have investigated how force production and modulation are encoded in the brain after stroke and how this relates to motor outcome. Thus, the purpose of this study was to (1) understand how past neuroimaging literature has contributed to establishing common patterns of brain reorganization during both relative and absolute force production after stroke, (2) examine how brain function is reorganized during force production and modulation in individuals with stroke, and (3) relate this task-related reorganization of brain function to the amount of paretic arm use after stroke. In the second chapter, we systematically reviewed all relevant literature examining brain activation during force production after stroke. The following chapters (chapters 3 and 4) applied functional magnetic resonance imaging (fMRI) to examine the neural correlates of force production and modulation after stroke. Chapter 2 supports differences in task-related brain activation dependent on features of stroke, such as severity and chronicity, as well as influence of rehabilitation. In addition, results suggest that activation of common motor areas of the brain during force production can be identified in relation to functional outcome after stroke. Results from the subsequent two chapters (3 and 4), demonstrate that brain function reorganizes in terms of absolute, and not relative force production after stroke. Specifically, stroke participants exhibit greater activation of motor areas than healthy controls when matched for absolute force production. Moreover, there is a relationship between paretic arm usage and brain activation, where stroke participants having less paretic arm use, as measured using wrist accelerometers, exhibit higher brain activation. Results of this thesis suggest that during absolute force production, brain activation may approach near maximal levels in stroke participants at lower forces than healthy controls. Furthermore, this effect may be amplified even further in subjects with less paretic arm usage, as increased activation in motor areas occurs in participants with less arm use after stroke. Ultimately, the results from this thesis will contribute to research relevant to brain reorganization in individuals with stroke and may lead to the development of new, beneficial therapeutic interventions that optimize brain reorganization and improve functional recovery after stroke. / Medicine, Faculty of / Graduate