Improving language mapping in clinical fMRI through assessment of grammar.

IntroductionBrain surgery in the language dominant hemisphere remains challenging due to unintended post-surgical language deficits, despite using pre-surgical functional magnetic resonance (fMRI) and intraoperative cortical stimulation. Moreover, patients are often recommended not to undergo surgery if the accompanying risk to language appears to be too high. While standard fMRI language mapping protocols may have relatively good predictive value at the group level, they remain sub-optimal on an individual level. The standard tests used typically assess lexico-semantic aspects of language, and they do not accurately reflect the complexity of language either in comprehension or production at the sentence level. Among patients who had left hemisphere language dominance we assessed which tests are best at activating language areas in the brain.MethodWe compared grammar tests (items testing word order in actives and passives, wh-subject and object questions, relativized subject and object clauses and past tense marking) with standard tests (object naming, auditory and visual responsive naming), using pre-operative fMRI. Twenty-five surgical candidates (13 females) participated in this study. Sixteen patients presented with a brain tumor, and nine with epilepsy. All participants underwent two pre-operative fMRI protocols: one including CYCLE-N grammar tests (items testing word order in actives and passives, wh-subject and object questions, relativized subject and object clauses and past tense marking); and a second one with standard fMRI tests (object naming, auditory and visual responsive naming). fMRI activations during performance in both protocols were compared at the group level, as well as in individual candidates.ResultsThe grammar tests generated more volume of activation in the left hemisphere (left/right angular gyrus, right anterior/posterior superior temporal gyrus) and identified additional language regions not shown by the standard tests (e.g., left anterior/posterior supramarginal gyrus). The standard tests produced more activation in left BA 47. Ten participants had more robust activations in the left hemisphere in the grammar tests and two in the standard tests. The grammar tests also elicited substantial activations in the right hemisphere and thus turned out to be superior at identifying both right and left hemisphere contribution to language processing.ConclusionThe grammar tests may be an important addition to the standard pre-operative fMRI testing

Hippocampal Pathway Plasticity Is Associated with the Ability to Form Novel Memories in Older Adults

White matter deterioration in the aging human brain contributes to cognitive decline. The fornix as main efferent hippocampal pathway is one of the tracts most strongly associated with age-related memory impairment. Its deterioration may predict conversion to Alzheimer’s dementia and its precursors. However, the associations between the ability to form novel memories, fornix microstructure and plasticity in response to training have never been tested. In the present study, 25 healthy older adults (15 women; mean age (SD): 69 (6) years) underwent an object-location training on three consecutive days. Behavioral outcome measures comprised recall performance on the training days, and on 1-day and 1-month follow up assessments. MRI at 3 Tesla was assessed before and after training. Fornix microstructure was determined by fractional anisotropy and mean diffusivity (MD) values from diffusion tensor imaging (DTI). In addition, hippocampal volumes were extracted from high-resolution images; individual hippocampal masks were further aligned to DTI images to determine hippocampal microstructure. Using linear mixed model analysis, we found that the change in fornix FA from pre- to post-training assessment was significantly associated with training success. Neither baseline fornix microstructure nor hippocampal microstructure or volume changes were significantly associated with performance. Further, models including control task performance (auditory verbal learning) and control white matter tract microstructure (uncinate fasciculus and parahippocampal cingulum) did not yield significant associations. Our results confirm that hippocampal pathways respond to short-term cognitive training, and extend previous findings by demonstrating that the magnitude of training-induced structural changes is associated with behavioral success in older adults. This suggests that the amount of fornix plasticity may not only be behaviorally relevant, but also a potential sensitive biomarker for the success of training interventions aimed at improving memory formation in older adults, a hypothesis to be evaluated in future studies

Age-related sensitivity to task-related modulation of language-processing networks.

It is widely assumed that cognitive functions decline with age and that these decrements are associated with age-related changes in patterns of functional activity. However, these functional changes may be due to age-related increased responsiveness to task demands and not to other cognitive processes on which neural and behavioural responses rely, since many ageing studies use task paradigms that may not be orthogonal to the cognitive function being investigated. Here we test this hypothesis in adults aged 20-86 years by combining measures of language comprehension, functional connectivity and neural integrity to identify functional networks activated in two language experiments with varying task demands. In one, participants listened to spoken sentences without performing an overt task (the natural listening condition) while in the other they performed a task in response to the same sentences. Using task-based ICA of fMRI, we identified a left-lateralised frontotemporal network associated with syntactic analysis, which remained consistently activated regardless of task demands. In contrast, in the task condition only a separate set of components showed task-specific activity in Opercular, Frontoparietal, and bilateral PFC. Only the PFC showed age-related increases in activation which, furthermore, was strongly mediated by grey matter health. These results suggest that, contrary to prevailing views, age-related changes in cognitive activation may be due in part to differential responses to task-related processes.RCUK, OtherThis is the final published version of the article "Age-related sensitivity to task-­related modulation of language-processing networks" published in Neuropsychologia here: http://www.sciencedirect.com/science/article/pii/S0028393214002802

White Matter Connectivity as a Neurophysiological Mechanism for Auditory Comprehension in the Neurologically Normal and Impaired

Objectives: As emerging brain imaging technologies enable research on white matter connectivity, studies have shown the importance of white matter tracts pertaining to auditory comprehension. The present study aimed to review the recent studies by looking at the relationship between white matter connectivity and language comprehension in several populations. Methods: A literature search identified 19 studies on the relationship between white matter connectivity and auditory comprehension in normal adults and patients with stroke and primary progressive aphasia. Results: Previous studies were analyzed and discussed in terms of phonological, semantic, and syntactic comprehension. Results indicated that dorsal tracts are mainly involved in phonological and syntactic comprehension, while ventral tracts in semantic and syntactic comprehension. In both normal and impaired groups, the arcuate fasciculus is involved in phonological processing, while the uncinated fasciculus, inferior longitudinal fasciculus, extreme capsule, fornix, and arcuate fasciculus are important in semantic comprehension. In syntactic comprehension, the superior longitudinal fasciculus and arcuate fasciculus play an important role. Auditory comprehension problems are affected by the extent to which white matter tracts are damaged. Several limitations of the previous research were also discussed. Conclusion: Further studies on the relationship between white matter connectivity and auditory comprehension need to consider such factors as participants, tasks, and scoring systems.ope

Propiedades psicométricas y datos normativos de la prueba ECCO_Senior: un instrumento para evaluar la comprensión gramatical en adultos mayores

El test ECCO_Senior se diseñó para evaluar la comprensión de oraciones en adultos mayores. Es una prueba corta y de fácil aplicación, que se ha empleado en distintos estudios previos. En el estudio participaron 670 personas, de 50 a 85 años de edad, que cumplían criterios de inclusión relativos al estatus cognitivo general, el estado de ánimo y porcentaje mínimo de aciertos en el test. Además de los test de cribado (MEC y GDS-15) y un cuestionario socio-demográfico, se aplicó a todos los participantes el test ECCO_Senior con el que se pueden obtener distintos índices (generales y específicos). Además de comprobar si existen diferencias entre los grupos según la edad y el nivel educativo, se evaluaron las propiedades psicométricas del test, incluyendo evidencias de validez en las que se probó la bondad de ajuste de tres modelos estructurales que sirven para identificar los índices que explican un mayor porcentaje de la varianza del constructo (comprensión de oraciones). Se ofrecen normas interpretativas del test por edad y nivel de estudios en los Apéndices. Los resultados indican que el test permite evaluar la comprensión de oraciones con una fiabilidad adecuada y es sensible a las dificultades que puede experimentar un adulto al realizar esta tarea. Los tres modelos muestran un buen ajuste y permiten concluir que las oraciones no ajustadas al orden sintáctico canónico y los distractores léxicos (si se considera el tipo de ítem) serían los mejores indicadores en términos del porcentaje de la varianza del constructo que explican.The ECCO_Senior test was designed to assess sentence comprehension in older adults. It is a short test and easy to apply, which has been used in different previous studies. The study involved 670 people, 50 to 85 years of age, who met inclusion criteria related to general cognitive status, mood and minimum percentage of performance in the test. In addition to the screening tests (MEC and GDS-15) and a socio-demographic questionnaire, the ECCO_Senior test was applied to all participants with which different indices (general and specific) can be obtained. In addition to checking if there are differences between the groups according to age and educational level, we evaluated the psychometric properties of the test, evidences of validity included, thus we tested the goodness of fit of three structural models that serve to identify the indices that explain a greater percentage of the variance of the construct (comprehension of sentences). Interpretive norms of the test are offered by age and level of studies in the Appendices. The results indicate that the test allows to evaluate sentence comprehension with adequate reliability and it is sensitive to the difficulties that an adult may experience when performing this task. The three models show a good fit and allow us to conclude that the sentences not adjusted to the canonical syntactic order and lexical foils (if the type of item is considered) would be the best indexes in terms of the percentage of construct’s variance they explain

Task Residual Functional Connectivity in Language and Attention Networks

The present study compared network specificity between task-residual and resting state data types. Task-residual data capitalizes on the remaining variance after the mean task-related signal is removed from the time series. This study also examined how inter- and intrahemispheric connectivity (bilateral homologous regions and regions contained within the same hemisphere, respectively) within the language and attention networks change as a result of age. Task-residual functional connectivity evidenced stronger laterality of the language and attention connections and thus greater network specificity than resting state functional connectivity of the same connections. Using task-residual data may be optimal for characterizing the synchronized fluctuations between regions of discrete networks. Furthermore, alterations in intrahemispheric functional connectivity can be observed as early as middle age within the domain-general attention domain

Diagnostic and prognostic role of semantic processing in preclinical Alzheimer's disease

Relatively spared during most of the timeline of normal aging, semantic memory shows a subtle yet measurable decline even during the pre-clinical stage of Alzheimer's disease. This decline is thought to reflect early neurofibrillary changes and impairment is detectable using tests of language relying on lexical-semantic abilities. A promising approach is the characterization of semantic parameters such as typicality and age of acquisition of words, and propositional density from verbal output. Seminal research like the Nun Study or the analysis of the linguistic decline of famous writers and politicians later diagnosed with Alzheimer's disease supports the early diagnostic value of semantic processing and semantic memory. Moreover, measures of these skills may play an important role for the prognosis of patients with mild cognitive impairment

Evidence against preserved syntactic comprehension in healthy aging

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