Functional MRI of Language Processing and Recovery

__Abstract__ My thesis describe the utility of implementing fMRI to investigate how the language system is reorganized in brain damaged patients. Specifically for aphasia research fMRI allows to show how specific language treatment methods have the potential to enhance language reorganization and therefore optimize language recovery. Chapter 2 provides a brief introduction into the basics of language fMRI and task design for current applications of this technique in both clinical and research practice. I also summarized how different language levels have been explored with a variety of language tasks that have improved the neuroanatomical models of language processing. Chapter 3 explores the cerebro-cerebellar language lateralization pattern in healthy participants and in brain tumors patients with a focus on atypical language representation. Chapter 4 studies the differential auditory processing of spoken and melodically intoned language underlying MIT therapy. Chapter 5 focuses on the neural substrate of phonological and semantic auditory, i.e. receptive, processing in healthy older adults, group who is more applicable to aphasia research. I specifically focused on the functional specialization within the left inferior frontal gyrus (IFG), given its proposed important role for the recovery of language functions in aphasia. Chapter 6 explores the relationship between language lateralization and language recovery, both at the level of language production and comprehension, in 36 patients with mild and severe chronic aphasia after left hemispheric stroke. Chapter 7 investigates whether intensive MIT induces a shift in language lateralization in sub-acute and chronic non-fluent aphasic patients

Neuropsychological profiles and neural correlates in typical and atypical variants of Alzheimer disease: A systematic qualitative review

Introduction: Neuropsychological symptoms and cortical atrophy patterns show similarities between typical Alzheimer’s Disease (AD) and its variants. Thus, correct diagnosis is difficult, leading to errors in the therapeutic process. Indeed, the challenge in cognitive neuroscience focuses on identifying key features of cognitive-linguistic profiles and improving the knowledge of neural correlates for accurate differential diagnosis between the heterogeneous profiles of typical and atypical AD. Aim: This systematic review aims to describe different AD profiles, considering their neuropsychological symptoms and neural correlates. Methods: The present study followed the PRISMA guidelines and included studies from the PubMed, ScienceDirect, Scopus, and Web of Science databases, published between 2011 and 2021. Results: Thirty-one articles were included in this systematic review for critical analysis. Results suggest significant declines in episodic and working memory and executive function. Likewise, in all groups, verbal fluency and visuospatial/visuoconstructive skills declined. However, these symptoms overlap between typical AD, logopenic variant primary progressive aphasia, posterior cortical atrophy, behavioural/dysexecutive or frontal variant AD, and corticobasal syndrome. On the other hand, the neural correlate showed a pattern of atrophy in frontal, temporal, parietal, and occipital areas, even compromising the cuneus and precuneus. Conclusion: Spontaneous language and semantic and phonological verbal fluency could be an important biomarker for differential diagnosis between typical AD and its atypical variants. Likewise, clinical assessment should consider using advanced neuroimaging techniques to establish early associations between brain dysfunction and neuropsychological performance, with particular attention to brain areas such as the cuneus and precuneus

Insight into the neurophysiological processes of melodically intoned language with functional MRI

Background: Melodic Intonation Therapy (MIT) uses the melodic elements of speech to improve language production in severe nonfluent aphasia. A crucial element of MIT is the melodically intoned auditory input: the patient listens to the therapist singing a target utterance. Such input of melodically intoned language facilitates production, whereas auditory input of spoken language does not. Methods: Using a sparse sampling fMRI sequence, we examined the differential auditory processing of spoken and melodically intoned language. Nineteen right-handed healthy volunteers performed an auditory lexical decision task in an event related design consisting of spoken and melodically intoned meaningful and meaningless items. The control conditions consisted of neutral utterances, either melodically intoned or spoken. Results: Irrespective of whether the items were normally spoken or melodically intoned, meaningful items showed greater activation in the supramarginal gyrus and inferior parietal lobule, predominantly in the left hemisphere. Melodically intoned language activated both temporal lobes rather symmetrically, as well as the right frontal lobe cortices, indicating that these regions are engaged in the acoustic complexity of melodically intoned stimuli. Compared to spoken language, melodically intoned language activated sensory motor regions and articulatory language networks in the left hemisphere, but only when meaningful language was used. Discussion: Our results suggest that the facilitatory effect of MIT may - in part - depend on an auditory input which combines melody and meaning. Conclusion: Combined melody and meaning provide a sound basis for the further investigation of melodic language processing in aphasic patients, and eventually the neurophysiological processes underlying MIT. Compared to spoken language, melodically intoned language activated sensory motor regions and articulatory language networks in the left hemisphere, but only when meaningful language was used. Our results suggest that the facilitatory effect of MIT may - in part - depend on an auditory input which combines melody and meaning. As such, they provide a sound basis for further investigation of melodic language processing in aphasic patients, and eventually the neurophysiological processes underlying MIT

Sensibilidad y especificidad del Test ScreeLing en usuarios afásicos en etapa aguda: un análisis preliminar

In Chile, aphasia is present in 20% to 30% of stroke patients. Currently, speech and language therapists do not have a standardized test to characterize aphasic patients' linguistics disorders at the acute phase. The aim of this study iso analyze the sensibility and specificity of the Spanish version of the ScreeLing test in aphasic patient post-stroke at the acute stage. To do so, in a transversal study design, acute aphasic patients (< 6 weeks post-stroke) and healthy adults were evaluated with the Spanish version of the ScreeLing test. Additionally, language comprehension and spontaneous speech were assessed with the shortened version of the Token Test and the Aphasia Severity Rating Scale, respectively. We calculated the Area Under ROC Curve (AUC) to choose the cut-off that provided the best balance between sensibility and specificity. We included 13 aphasic patients and 56 healthy adults. The best balance between sensibility and specificity was found to be with 67 points, with a sensibility of 94,6% and specificity of 100%. The AUC ROC was 0,99 (IC 95%: 0,97-1,00). For the subtest measuring syntax and phonology, the cut-off score was 21 points, and for the semantic subtest, 22 points. In conclusion, the Spanish version of the ScreeLing test, similar to its original Dutch version, demonstrated high specificity and sensibility to detect linguistic deficits in acute aphasic patients post-stroke. Future efforts aim to increase the sample size of patients considering different language severity profiles.En Chile, entre un 20% y un 38% de los usuarios que sufren un ataque cerebro-vascular (ACV) presentan afasia. Pese a su alta prevalencia no existen herramientas validadas que permitan realizar una caracterización lingüística temprana de la afasia. Por lo anterior, el objetivo del presente trabajo es analizar la sensibilidad y especificidad de la versión en español del ScreeLing en una muestra de usuarios afásicos después de producido un ACV. Se trata de un estudio transversal analítico en el cual se aplicó el test ScreeLing a 13 usuarios afásicos tras primer evento de ACV en etapa aguda (< 6 semanas tras ACV) y a 56 adultos neurológicamente sanos. Adicionalmente, se evaluó el nivel comprensivo y el lenguaje espontáneo de usuarios con afasia, con la versión abreviada del Token Test y Escala de Severidad de la Afasia (ASRS). Se construyeron modelos mediante regresiones logísticas, obteniendo sus respectivas áreas bajo la curva ROC. Los resultados muestran que el equilibrio entre sensibilidad y especificidad para el puntaje global del test ScreeLing se estableció en 67 puntos, obteniendo una sensibilidad del 94,6% y especificidad del 100%. El área bajo la curva ROC alcanzó 0,99 (IC 95%: 0,97-1,00). En las subpruebas sintáctica y fonológica se alcanzó un puntaje de corte de 21 puntos, mientras que en la subprueba semántica se lograron 22 puntos. Se concluye que el ScreeLing en español posee una alta sensibilidad y especificidad para la detección de déficits lingüísticos post ACV similar a los resultados encontrados en la versión original del test en holandés. Esfuerzos futuros deben concentrarse en ampliar la muestra de usuarios afásicos con distintos perfiles de severidad

Standardized evaluation of algorithms for computer-aided diagnosis of dementia based on structural MRI: The CADDementia challenge

Algorithms for computer-aided diagnosis of dementia based on structural MRI have demonstrated high performance in the literature, but are difficult to compare as different data sets and methodology were used for evaluation. In addition, it is unclear how the algorithms would perform on previously unseen data, and thus, how they would perform in clinical practice when there is no real opportunity to adapt the algorithm to the data at hand. To address these comparability, generalizability and clinical applicability issues, we organized a grand challenge that aimed to objectively compare algorithms based on a clinically representative multi-center data set. Using clinical practice as the starting point, the goal was to reproduce the clinical diagnosis. Therefore, we evaluated algorithms for multi-class classification of three diagnostic groups: patients with probable Alzheimer's disease, patients with mild cognitive impairment and healthy controls. The diagnosis based on clinical criteria was used as reference standard, as it was the best available reference despite its known limitations. For evaluation, a previously unseen test set was used consisting of 354 T1-weighted MRI scans with the diagnoses blinded. Fifteen research teams participated with a total of 29 algorithms. The algorithms were trained on a small training set (n = 30) and optionally on data from other sources (e.g., the Alzheimer's Disease Neuroimaging Initiative, the Australian Imaging Biomarkers and Lifestyle flagship study of aging). The best performing algorithm yielded an accuracy of 63.0% and an area under the receiver-operating-characteristic curve (AUC) of 78.8%. In general, the best performances were achieved using feature extraction based on voxel-based morphometry or a combination of features that included volume, cortical thickness, shape and intensity. The challenge is open for new submissions via the web-based framework: http://caddementia.grand-challenge.org

Imageability ratings across languages

Imageability is a psycholinguistic variable that indicates how well a word gives rise to a mental image or sensory experience. Imageability ratings are used extensively in psycholinguistic, neuropsychological, and aphasiological studies. However, little formal knowledge exists about whether and how these ratings are associated between and within languages. Fifteen imageability databases were cross-correlated using nonparametric statistics. Some of these corresponded to unpublished data collected within a European research network-the Collaboration of Aphasia Trialists (COST IS1208). All but four of the correlations were significant. The average strength of the correlations (rho = .68) and the variance explained (R (2) = 46%) were moderate. This implies that factors other than imageability may explain 54% of the results. Imageability ratings often correlate across languages. Different possibly interacting factors may explain the moderate strength and variance explained in the correlations: (1) linguistic and cultural factors; (2) intrinsic differences between the databases; (3) range effects; (4) small numbers of words in each database, equivalent words, and participants; and (5) mean age of the participants. The results suggest that imageability ratings may be used cross-linguistically. However, further understanding of the factors explaining the variance in the correlations will be needed before research and practical recommendations can be made

5to. Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad. Memoria académica

El V Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad, CITIS 2019, realizado del 6 al 8 de febrero de 2019 y organizado por la Universidad Politécnica Salesiana, ofreció a la comunidad académica nacional e internacional una plataforma de comunicación unificada, dirigida a cubrir los problemas teóricos y prácticos de mayor impacto en la sociedad moderna desde la ingeniería. En esta edición, dedicada a los 25 años de vida de la UPS, los ejes temáticos estuvieron relacionados con la aplicación de la ciencia, el desarrollo tecnológico y la innovación en cinco pilares fundamentales de nuestra sociedad: la industria, la movilidad, la sostenibilidad ambiental, la información y las telecomunicaciones. El comité científico estuvo conformado formado por 48 investigadores procedentes de diez países: España, Reino Unido, Italia, Bélgica, México, Venezuela, Colombia, Brasil, Estados Unidos y Ecuador. Fueron recibidas un centenar de contribuciones, de las cuales 39 fueron aprobadas en forma de ponencias y 15 en formato poster. Estas contribuciones fueron presentadas de forma oral ante toda la comunidad académica que se dio cita en el Congreso, quienes desde el aula magna, el auditorio y la sala de usos múltiples de la Universidad Politécnica Salesiana, cumplieron respetuosamente la responsabilidad de representar a toda la sociedad en la revisión, aceptación y validación del conocimiento nuevo que fue presentado en cada exposición por los investigadores. Paralelo a las sesiones técnicas, el Congreso contó con espacios de presentación de posters científicos y cinco workshops en temáticas de vanguardia que cautivaron la atención de nuestros docentes y estudiantes. También en el marco del evento se impartieron un total de ocho conferencias magistrales en temas tan actuales como la gestión del conocimiento en la universidad-ecosistema, los retos y oportunidades de la industria 4.0, los avances de la investigación básica y aplicada en mecatrónica para el estudio de robots de nueva generación, la optimización en ingeniería con técnicas multi-objetivo, el desarrollo de las redes avanzadas en Latinoamérica y los mundos, la contaminación del aire debido al tránsito vehicular, el radón y los riesgos que representa este gas radiactivo para la salud humana, entre otros

Laboratorio en abierto: aPrendiendo a CopiaR el ADN

El objetivo principal del proyecto es la puesta a punto de recursos educativos en abierto (REA) dirigidos a los alumnos de secundaria. El punto de partida será plantear diferentes retos y situaciones que se pueden resolver utilizando distintos recursos científicos, para decidir qué recurso es el más adecuado y cómo se aplica. En esta propuesta la resolución de los problemas planteados estaría basada en la aplicación de una herramienta que ha revolucionado la genética y biología, la reacción en Cadena de la Polimerasa, conocida como PCR

Laboratorio en abierto: aprendendiendo a copiar ADN.2

El objetivo principal del proyecto es la puesta a punto de recursos educativos en abierto (REA) dirigidos a los alumnos de secundaria. La propuesta pretende desarrollar habilidades, para la resolución de problemas científicos, a través de retos que despierten el interés y la imaginación de los alumnos de secundaria. En esta propuesta la resolución de los problemas planteados estaría basada en la aplicación de una herramienta que ha revolucionado la genética y biología, la reacción en Cadena de la Polimerasa, conocida como PCR

Insight into the neurophysiological processes of melodically intoned language with functional MRI

textabstractBackground: Melodic Intonation Therapy (MIT) uses the melodic elements of speech to improve language production in severe nonfluent aphasia. A crucial element of MIT is the melodically intoned auditory input: the patient listens to the therapist singing a target utterance. Such input of melodically intoned language facilitates production, whereas auditory input of spoken language does not. Methods: Using a sparse sampling fMRI sequence, we examined the differential auditory processing of spoken and melodically intoned language. Nineteen right-handed healthy volunteers performed an auditory lexical decision task in an event related design consisting of spoken and melodically intoned meaningful and meaningless items. The control conditions consisted of neutral utterances, either melodically intoned or spoken. Results: Irrespective of whether the items were normally spoken or melodically intoned, meaningful items showed greater activation in the supramarginal gyrus and inferior parietal lobule, predominantly in the left hemisphere. Melodically intoned language activated both temporal lobes rather symmetrically, as well as the right frontal lobe cortices, indicating that these regions are engaged in the acoustic complexity of melodically intoned stimuli. Compared to spoken language, melodically intoned language activated sensory motor regions and articulatory language networks in the left hemisphere, but only when meaningful language was used. Discussion: Our results suggest that the facilitatory effect of MIT may - in part - depend on an auditory input which combines melody and meaning. Conclusion: Combined melody and meaning provide a sound basis for the further investigation of melodic language processing in aphasic patients, and eventually the neurophysiological processes underlying MIT. Compared to spoken language, melodically intoned language activated sensory motor regions and articulatory language networks in the left hemisphere, but only when meaningful language was used. Our results suggest that the facilitatory effect of MIT may - in part - depend on an auditory input which combines melody and meaning. As such, they provide a sound basis for further investigation of melodic language processing in aphasic patients, and eventually the neurophysiological processes underlying MIT