Imaging short- and long-term training success in chronic aphasia

<p>Abstract</p> <p>Background</p> <p>To date, functional imaging studies of treatment-induced recovery from chronic aphasia only assessed short-term treatment effects after intensive language training. In the present study, we show with functional magnetic resonance imaging (fMRI), that different brain regions may be involved in immediate versus long-term success of intensive language training in chronic post-stroke aphasia patients.</p> <p>Results</p> <p>Eight patients were trained daily for three hours over a period of two weeks in naming of concrete objects. Prior to, immediately after, and eight months after training, patients overtly named trained and untrained objects during event-related fMRI. On average the patients improved from zero (at baseline) to 64.4% correct naming responses immediately after training, and treatment success remained highly stable at follow-up. Regression analyses showed that the degree of short-term treatment success was predicted by increased activity (compared to the pretraining scan) bilaterally in the hippocampal formation, the right precuneus and cingulate gyrus, and bilaterally in the fusiform gyri. A different picture emerged for long-term training success, which was best predicted by activity increases in the right-sided Wernicke's homologue and to a lesser degree in perilesional temporal areas.</p> <p>Conclusion</p> <p>The results show for the first time that treatment-induced language recovery in the chronic stage after stroke is a dynamic process. Initially, brain regions involved in memory encoding, attention, and multimodal integration mediated treatment success. In contrast, long-term treatment success was predicted mainly by activity increases in the so-called 'classical' language regions. The results suggest that besides perilesional and homologue language-associated regions, functional integrity of domain-unspecific memory structures may be a prerequisite for successful (intensive) language interventions.</p

The Selectivity and Functional Connectivity of the Anterior Temporal Lobes

One influential account asserts that the anterior temporal lobe (ATL) is a domain-general hub for semantic memory. Other evidence indicates it is part of a domain-specific social cognition system. Arbitrating these accounts using functional magnetic resonance imaging has previously been difficult because of magnetic susceptibility artifacts in the region. The present study used parameters optimized for imaging the ATL, and had subjects encode facts about unfamiliar people, buildings, and hammers. Using both conjunction and region of interest analyses, person-selective responses were observed in both the left and right ATL. Neither building-selective, hammer-selective nor domain-general responses were observed in the ATLs, although they were observed in other brain regions. These findings were supported by “resting-state” functional connectivity analyses using independent datasets from the same subjects. Person-selective ATL clusters were functionally connected with the brain's wider social cognition network. Rather than serving as a domain-general semantic hub, the ATLs work in unison with the social cognition system to support learning facts about others

Personal Memories and Generic Mental Representations

The paper focuses on the particular structure of the content of so-called generic memories, specifically of those of recurring events from one's past. This way of remembering has two central features that are in tension to each other: what is mentally represented is both rather specific as one is typically simulating a scene and sufficiently abstract as the represented scene stands for a series of similar former events. It will be argued that the phenomenon can be adequately described as a mental state representing personal event prototypes. This description further allows to account for the dynamic process of remembering, in which, depending on the context, different forms of personal remembering may come to the fore

Online neurostimulation of Broca's area does not interfere with syntactic predictions: A combined TMS-EEG approach to basic linguistic combination

Categorical predictions have been proposed as the key mechanism supporting the fast pace of syntactic composition in human language. Accordingly, grammar-based expectations facilitate the analysis of incoming syntactic information—e.g., hearing the determiner “the” enhances the prediction of a noun—which is then checked against a single or few other word categories. Previous functional neuroimaging studies point towards Broca’s area in the left inferior frontal gyrus (IFG) as one fundamental cortical region involved in categorical prediction during on-line language processing. Causal evidence for this hypothesis is however still missing. In this study, we combined Electroencephalography (EEG) and Transcranial Magnetic Stimulation (TMS) to test whether Broca’s area is functionally relevant in predictive mechanisms for language. Specifically, we transiently perturbed Broca’s area during the categorical prediction phase in two-word constructions, while simultaneously measuring the Event-Related Potential (ERP) correlates of syntactic composition. We reasoned that if Broca’s area is involved in predictive mechanisms for syntax, disruptive TMS during the processing of the first word (determiner/pronoun) would mitigate the difference in ERP responses for predicted and unpredicted categories when composing basic phrases and sentences. Contrary to our hypothesis, perturbation of Broca’s area at the predictive stage did not affect the ERP correlates of basic composition. The correlation strength between the electrical field induced by TMS and the magnitude of the EEG response on the scalp further confirmed this pattern. We discuss the present results in light of an alternative account of the role of Broca’s area in syntactic composition, namely the bottom-up integration of words into constituents

Language assessment in mesial temporal lobe epilepsy : correlations with structural and functional neuroimaging

Orientadores: Fernando Cendes, Marcio Luiz Figueredo BalthazarTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências MédicasResumo: A epilepsia de lobo temporal (ELT) é o tipo de epilepsia mais comum no adulto e comorbidades cognitivas podem acompanhá-la, como prejuízos de memória e linguagem. Nesta população é esperada uma maior incidência de pessoas com lateralização atípica para linguagem (LAL), 20% contra 5% da população saudável. Alguns fatores são apontados como preditores: dominância manual, sinistralidade familiar e insulto cerebral precoce e em hemisfério esquerdo. A linguagem nesses pacientes tem sido estudada há décadas, mas ultimamente a técnica de ressonância magnética funcional (fMRI) vem substituindo o teste de WADA e proporcionado uma série de novos métodos e paradigmas para estudar essa função in vivo, inclusive em indivíduos saudáveis. Portanto, o objetivo desse estudo foi delinear os subtipos de ELT, com atrofia esquerda (AHE), direita (AHD) e sem atrofia (negAH) hipocampal comparando-os com controles, quanto a aspectos de linguagem. Os resultados foram dispostos em dois artigos. O primeiro tratou da comparação de dois paradigmas de fMRI de linguagem baseados em decisão semântica. Neste artigo, 24 indivíduos saudáveis foram submetidos a duas versões de tarefa de linguagem: versão complexa e versão fácil. Ambas foram efetivas, porém a versão complexa produziu resultados mais robustos para a avaliação da linguagem. Logo, foi a versão eleita para conduzir o estudo com os pacientes ELT. O segundo resultado, foi exposto no artigo que comparou pacientes com AHD (n=31), AHE (n=32) e negAH (n=30), além de controles (n=101). Esse artigo investigou o impacto da atrofia hipocampal no perfil de linguagem em diferentes subtipos de ELT; avaliando a incidência e fatores preditivos de lateralização de linguagem, sua relação com o padrão de ativação da fMRI em regiões associadas à linguagem; comparação entre os grupos quanto ao padrão de ativação de linguagem e conectividade funcional, além da comparação do desempenho no teste de nomeação de Boston e sua correlação com o padrão de ativação da tarefa. Os resultados apontaram para frequência de LAL semelhante em todos os grupos e somente a dominância manual como preditor de dominância hemisférica para linguagem, porém, de forma distinta em cada grupo de acordo com as regiões de interesse. O padrão de ativação da linguagem e a análise entre regiões de interesse (ROI-to-ROI) apontaram pior desempenho do grupo AHE em relação aos grupos controle e negAH. A análise entre o giro frontal médio esquerdo e o cérebro todo (seed-based-voxel) mostrou que todos os grupos de pacientes apresentam conectividade funcional diminuída em relação aos controles, além de diferenças par a par entre os grupos de pacientes. O melhor desempenho em nomeação se correlacionou com maior ativação em áreas de linguagem nos grupos AHD e negAH. Este estudo concluiu que pacientes com AHE apresentaram pior desempenho em nomeação, ativação e conectividade funcional, seguidos pelos pacientes com AHD, enquanto os pacientes negAH apresentaram alterações discretas em comparação aos controles. Esta tese mostra que apesar dos vários estudos de fMRI sobre linguagem, novos trabalhos com diferentes metodologias e paradigmas são necessários para compreender melhor as alterações de linguagem em subtipos de ELTAbstract: Temporal lobe epilepsy is the most common type of epilepsy in adults and is also associated with cognitive comorbidities, such as memory and language impairments, especially in temporal lobe epilepsy (TLE). In this population, a higher incidence of people with atypical language lateralization (ALL) is expected; 20% against 5% of the healthy people. Some factors are pointed as predictors: manual dominance, left-hand familial history, as well as early insult and left hemisphere lesion. Language in these patients has been studied for decades. Lately functional magnetic resonance (fMRI) technique has been replacing the WADA test and has provided new methods and paradigms to study this function in vivo, including in healthy volunteers. Therefore, the objective of this study was to delineate the language aspects in TLE with left (LHA) and right (RHA) hippocampal atrophy and patients without hippocampal atrophy (nonAH), comparing them to controls. The results were set out in two manuscripts. The first, showed the translation of a well-established language fMRI paradigm based on semantic decision and comparison of two versions: easy and complex task in 24 healthy subjects. Both versions were effective, but the complex version produced more robust results for the evaluation of the language in our patients. Therefore, complex version was chosen to conduct the study with TLE patients. The second result was presented in the manuscript which compared patients with RHA (n=31), LHA (n=32), nonHA (n=30) and controls (n=101). In this paper analyzes were performed to investigate the impact of HA on language to obtain a profile of the language in different subtypes of TLE. Analyzes were conducted to acquire the incidence of language lateralization, predictive factors and correlation with fMRI activation pattern in regions associated with language; comparison between groups regarding language activation pattern and functional connectivity, as well as a comparison of performance on the Boston naming test and its correlation with the task activation pattern. The results pointed to a similar frequency of ALL in all groups and only manual dominance as a predictor of hemispheric dominance for language. However, each group was different according to the specific regions of interest. Language activation pattern and ROI-to-ROI analysis showed that LHA presented reduced activation compared with controls and nonHA groups. Seed-based-voxel analysis showed that all groups of patients had reduced functional connectivity in relation to controls, as well as differences among patients. The higher scores on naming performance was correlated with greater activation in language areas only in RHA and nonHA groups. We concluded that patients with LHA presented worse performance in naming, activation and functional connectivity, followed by RHA, and nonHA patients were more similar to controls. This thesis shows that despite of several language fMRI studies, further investigations using different methodologies and paradigms are necessary for better undestanding of language alterations in different TLE subtypesDoutoradoFisiopatologia MédicaDoutora em Ciências2012/05364-817229/12-0FAPESPCAPESBE

Inductive Pattern Formation

With the extended computational limits of algorithmic recursion, scientific investigation is transitioning away from computationally decidable problems and beginning to address computationally undecidable complexity. The analysis of deductive inference in structure-property models are yielding to the synthesis of inductive inference in process-structure simulations. Process-structure modeling has examined external order parameters of inductive pattern formation, but investigation of the internal order parameters of self-organization have been hampered by the lack of a mathematical formalism with the ability to quantitatively define a specific configuration of points. This investigation addressed this issue of quantitative synthesis. Local space was developed by the Poincare inflation of a set of points to construct neighborhood intersections, defining topological distance and introducing situated Boolean topology as a local replacement for point-set topology. Parallel development of the local semi-metric topological space, the local semi-metric probability space, and the local metric space of a set of points provides a triangulation of connectivity measures to define the quantitative architectural identity of a configuration and structure independent axes of a structural configuration space. The recursive sequence of intersections constructs a probabilistic discrete spacetime model of interacting fields to define the internal order parameters of self-organization, with order parameters external to the configuration modeled by adjusting the morphological parameters of individual neighborhoods and the interplay of excitatory and inhibitory point sets. The evolutionary trajectory of a configuration maps the development of specific hierarchical structure that is emergent from a specific set of initial conditions, with nested boundaries signaling the nonlinear properties of local causative configurations. This exploration of architectural configuration space concluded with initial process-structure-property models of deductive and inductive inference spaces. In the computationally undecidable problem of human niche construction, an adaptive-inductive pattern formation model with predictive control organized the bipartite recursion between an information structure and its physical expression as hierarchical ensembles of artificial neural network-like structures. The union of architectural identity and bipartite recursion generates a predictive structural model of an evolutionary design process, offering an alternative to the limitations of cognitive descriptive modeling. The low computational complexity of these models enable them to be embedded in physical constructions to create the artificial life forms of a real-time autonomously adaptive human habitat

Neural processes underpinning episodic memory

Episodic memory is the memory for our personal past experiences. Although numerous functional magnetic resonance imaging (fMRI) studies investigating its neural basis have revealed a consistent and distributed network of associated brain regions, surprisingly little is known about the contributions individual brain areas make to the recollective experience. In this thesis I address this fundamental issue by employing a range of different experimental techniques including neuropsychological testing, virtual reality environments, whole brain and high spatial resolution fMRI, and multivariate pattern analysis. Episodic memory recall is widely agreed to be a reconstructive process, one that is known to be critically reliant on the hippocampus. I therefore hypothesised that the same neural machinery responsible for reconstruction might also support ‘constructive’ cognitive functions such as imagination. To test this proposal, patients with focal damage to the hippocampus bilaterally were asked to imagine new experiences and were found to be impaired relative to matched control participants. Moreover, driving this deficit was a lack of spatial coherence in their imagined experiences, pointing to a role for the hippocampus in binding together the disparate elements of a scene. A subsequent fMRI study involving healthy participants compared the recall of real memories with the construction of imaginary memories. This revealed a fronto-temporo-parietal network in common to both tasks that included the hippocampus, ventromedial prefrontal, retrosplenial and parietal cortices. Based on these results I advanced the notion that this network might support the process of ‘scene construction’, defined as the generation and maintenance of a complex and coherent spatial context. Furthermore, I argued that this scene construction network might underpin other important cognitive functions besides episodic memory and imagination, such as navigation and thinking about the future. It is has been proposed that spatial context may act as the scaffold around which episodic memories are built. Given the hippocampus appears to play a critical role in imagination by supporting the creation of a rich coherent spatial scene, I sought to explore the nature of this hippocampal spatial code in a novel way. By combining high spatial resolution fMRI with multivariate pattern analysis techniques it proved possible to accurately determine where a subject was located in a virtual reality environment based solely on the pattern of activity across hippocampal voxels. For this to have been possible, the hippocampal population code must be large and non-uniform. I then extended these techniques to the domain of episodic memory by showing that individual memories could be accurately decoded from the pattern of activity across hippocampal voxels, thus identifying individual memory traces. I consider these findings together with other recent advances in the episodic memory field, and present a new perspective on the role of the hippocampus in episodic recollection. I discuss how this new (and preliminary) framework compares with current prevailing theories of hippocampal function, and suggest how it might account for some previously contradictory data