Adiponectin and resistin modulate the progression of Alzheimer´s disease in a metabolic syndrome model.

Metabolic syndrome (MetS), a cluster of metabolic conditions that include obesity, hyperlipidemia, and insulin resistance, increases the risk of several aging-related brain diseases, including Alzheimer's disease (AD). However, the underlying mechanism explaining the link between MetS and brain function is poorly understood. Among the possible mediators are several adipose-derived secreted molecules called adipokines, including adiponectin (ApN) and resistin, which have been shown to regulate brain function by modulating several metabolic processes. To investigate the impact of adipokines on MetS, we employed a diet-induced model to induce the various complications associated with MetS. For this purpose, we administered a high-fat diet (HFD) to both WT and APP/PSN1 mice at a pre-symptomatic disease stage. Our data showed that MetS causes a fast decline in cognitive performance and stimulates Aß42 production in the brain. Interestingly, ApN treatment restored glucose metabolism and improved cognitive functions by 50% while decreasing the Aß42/40 ratio by approximately 65%. In contrast, resistin exacerbated Aß pathology, increased oxidative stress, and strongly reduced glucose metabolism. Together, our data demonstrate that ApN and resistin alterations could further contribute to AD pathology.

Phonological and Semantic Fluency in Alzheimer's Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Semantic and Phonological fluency (SF and PF) are routinely evaluated in patients with Alzheimer's disease (AD). There are disagreements in the literature regarding which fluency task is more affected while developing AD. Most studies focus on SF assessment, given its connection with the temporoparietal amnesic system. PF is less reported, it is related to working memory, which is also impaired in probable and diagnosed AD. Differentiating between performance on these tasks might be informative in early AD diagnosis, providing an accurate linguistic profile. OBJECTIVE: Compare SF and PF performance in healthy volunteers, volunteers with probable AD, and patients with AD diagnosis, considering the heterogeneity of age, gender, and educational level variables. METHODS: A total of 8 studies were included for meta-analysis, reaching a sample size of 1,270 individuals (568 patients diagnosed with AD, 340 with probable AD diagnosis, and 362 healthy volunteers). RESULTS: The three groups consistently performed better on SF than PF. When progressing to a diagnosis of AD, we observed a significant difference in SF and PF performance across our 3 groups of interest (p = 0.04). The age variable explained a proportion of this difference in task performance across the groups, and as age increases, both tasks equally worsen. CONCLUSION: The performance of SF and PF might play a differential role in early AD diagnosis. These tasks rely on partially different neural bases of language processing. They are thus worth exploring independently in diagnosing normal aging and its transition to pathological stages, including probable and diagnosed AD.

Age- and Sex-Associated Glucose Metabolism Decline in a Mouse Model of Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is characterized by a high etiological and clinical heterogeneity, which has obscured the diagnostic and treatment efficacy, as well as limited the development of potential drugs. Sex differences are among the risk factors that contribute to the variability of disease manifestation. Unlike men, women are at greater risk of developing AD and suffer from higher cognitive deterioration, together with important changes in pathological features. Alterations in glucose metabolism are emerging as a key player in the pathogenesis of AD, which appear even decades before the presence of clinical symptoms. OBJECTIVE: We aimed to study whether AD-related sex differences influence glucose metabolism. METHODS: We used male and female APPswe/PS1dE9 (APP/PS1) transgenic mice of different ages to examine glucose metabolism effects on AD development. RESULTS: Our analysis suggests an age-dependent decline of metabolic responses, cognitive functions, and brain energy homeostasis, together with an increase of Aß levels in both males and females APP/PS1 mice. The administration of Andrographolide (Andro), an anti-inflammatory and anti-diabetic compound, was able to restore several metabolic disturbances, including the glycolytic and the pentose phosphate pathway fluxes, ATP levels, AMPKα activity, and Glut3 expression in 8-month-old mice, independent of the sex, while rescuing these abnormalities only in older females. Similarly, Andro also prevented Aß accumulation and cognitive decline in all but old males. CONCLUSION: Our study provides insight into the heterogeneity of the disease and supports the use of Andro as a potential drug to promote personalized medicine in AD.

Alternative language paradigms for functional magnetic resonance imaging as presurgical tools for inducing crossed cerebro-cerebellar language activations in brain tumor patients.

OBJECTIVES: Crossed cerebro-cerebellar BOLD activations have recently come to light as additional diagnostic features for patients with brain tumors. The covert verb generation (VG) task is a widely used language paradigm to determine these language-related crossed activations. Here we demonstrate these crossed activations in two additional language paradigms, the semantic and phonological association tasks. We propose the merit of these tasks to language lateralization determination in the clinic as they are easy to monitor and suitable for patients with aphasia. METHODS: Patients with brain tumors localized at different cortical sites (n = 71) performed three language paradigms, namely the VG task as well as the semantic (SA) and phonological (PA) association tasks with button-press responses. Respective language activations in disparate cortical regions and the cerebellum were assigned laterality. Agreements in laterality between the two new tasks and the verb generation task were tested using Cohen's kappa. RESULTS: Both tasks significantly agreed in cortical and cerebellar lateralization with the verb generation task in patients. Additionally, a McNemar test confirmed the presence of crossed activations in the cortex and the cerebellum in the entire subject population. CONCLUSION: We demonstrated that the semantic and phonological association tasks resulted in crossed cerebro-cerebellar language lateralization activations as those observed due to the covert verb generation task. This may suggest the possibility of these tasks being used conjointly with the traditional verb generation task, especially for subjects that may be unable to perform the latter. KEY POINTS: • The semantic and phonological association tasks can be useful as additional presurgical fMRI language lateralization paradigms for brain tumor patients along with the standard verb generation task. • All three tasks also confirm the presence of crossed cerebro-cerebellar language activations in the current subject population.

[Evaluation of the crossed cerebro-cerebellar activation to determine language lateralization in patients with brain tumors]. / Evaluación de la actividad cerebro-cerebelar cruzada para determinar la lateralidad del lenguaje en pacientes con tumores cerebrales.

BACKGROUND: The crossed cerebro-cerebellar (CCC) activation facilitates the diagnosis of cortical language lateralization, but needs to be explored with language tasks suitable for patients with different age ranges, educational attainment and eventual presence of language deficits. AIM: To determine the effect of demographic variables in the performance of three language tasks in healthy volunteers and to determine the CCC activation of these tasks as a functional magnetic resonance imaging (fMRI) paradigm in brain tumor patients. MATERIAL AND METHODS: The behavioral performance (correct responses and reaction time) of three language tasks (verbal fluency, semantic and phonological decision tasks) was first examined in 76 healthy volunteers balanced by age and educational level. Later, these tasks were implemented as fMRI paradigms to explore CCC language activation of 20 patients with potential diagnosis of brain tumors. RESULTS: The performance of the verbal fluency task was affected by age. The CCC language activation was reproducible with the semantic and phonological tasks. The combination of the tasks determined typical and atypical language lateralization in 60% and 40% of our patients, respectively. CONCLUSIONS: The verbal fluency task must be implemented with care as a clinical fMRI paradigm. Our results suggest that semantic and phonological tasks can be a good alternative for brain tumor patients with language deficits.

3D simulation of aneurysm clipping: Data analysis.

Aneurysm clipping requires the proficiency of several skills, yet the traditional way of practicing them has been recently challenged. The use of simulators could be an alternative educational tool. The aim of this data analysis is to provide further evaluation of a reusable low-cost 3D printed training model we developed for aneurysm clipping [1]. The simulator was designed to replicate the bone structure, arteries and targeted aneurysms. Thirty-two neurosurgery residents performed a craniotomy and aneurysm clipping using the model and then filled out a survey. The survey was designed in two parts: a 5-point Likert scale questionnaire and three questions requiring written responses [1]. Two dimensions of the model were evaluated by the questionnaire: the face validity, assessed by 5 questions about the realism of the model, and the content validity, assessed by 6 questions regarding the usefulness of the model during the different steps of the training procedure. The three questions requiring written responses referred to the strengths and weaknesses of the simulator and a global yes/no question as to whether or not they would repeat the experience. Demographic data, experience level and survey responses of the residents were grouped in a dataset [2]. A descriptive analysis was performed for each dimension. Then, the groups were compared according to their level of expertise (Junior and Senior groups) with an independent sample t-test. A Confirmatory Factor Analysis (CFA) was estimated, using a Weighted Least Squares Mean Variance adjusted (WLSMV) which works best for the ordinal data [3]. Fitness was calculated using chi-square (χ2) test, Comparative Fit Index (CFI), Tucker-Lewis Index (TLI), and the Root Mean Square Error of Approximation (RMSEA). A non-significant χ2, CFI and TLI greater than 0.90 and RMSEA < 0.08 were considered an acceptable fit [4]. All data analysis was performed using IBM SPSS 23.0 statistical software. Data are reported as mean + standard deviation (SD). A probability p < 0.05 was considered significant. Exploratory Factor Analysis was done to explore the factorial structure of the 11-items scale in the sample, first we performed a principal components analysis. The Kaiser-Meyer-Olkin measure verified the sampling adequacy for the analysis (KMO = 0.784; Bartlett's Test of Sphericity χ2 (55) = 243.44, p < .001), indicating correlation is adequate for factor analysis. Considering Eigen values greater than 1, a two-factor solution explained 73.1% of the variance but left one item in factor 2 (Q 11). The results of this factor analysis are presented in Table 1. Confirmatory Factor Analysis, considering only the 10 items in the first factor (removing question 11 of our model), was performed. This model reached the following fit: χ2 (35) = 38.821, p > .05; CFI = 0.997; TLI = 0.996; RMSEA 0.058, without any error terms to exhibit covariance. Regarding the reliability of the questionnaire, the internal consistency was explored in the 10 items selected in the confirmatory factor analysis with an alpha coefficient (α = 0.941).

Evaluación de la actividad cerebro-cerebelar cruzada para determinar la lateralidad del lenguaje en pacientes con tumores cerebrales / Evaluation of the crossed cerebro-cerebellar activation to determine language lateralization in patients with brain tumors

Background: The crossed cerebro-cerebellar (CCC) activation facilitates the diagnosis of cortical language lateralization, but needs to be explored with language tasks suitable for patients with different age ranges, educational attainment and eventual presence of language deficits. Aim: To determine the effect of demographic variables in the performance of three language tasks in healthy volunteers and to determine the CCC activation of these tasks as a functional magnetic resonance imaging (fMRI) paradigm in brain tumor patients. Material and Methods: The behavioral performance (correct responses and reaction time) of three language tasks (verbal fluency, semantic and phonological decision tasks) was first examined in 76 healthy volunteers balanced by age and educational level. Later, these tasks were implemented as fMRI paradigms to explore CCC language activation of 20 patients with potential diagnosis of brain tumors. Results: The performance of the verbal fluency task was affected by age. The CCC language activation was reproducible with the semantic and phonological tasks. The combination of the tasks determined typical and atypical language lateralization in 60% and 40% of our patients, respectively. Conclusions: The verbal fluency task must be implemented with care as a clinical fMRI paradigm. Our results suggest that semantic and phonological tasks can be a good alternative for brain tumor patients with language deficits.

Reusable Low-Cost 3D Training Model for Aneurysm Clipping.

BACKGROUND: Aneurysm clipping requires the proficiency of several skills, yet the traditional way of practicing them has been recently challenged, especially by the growth of endovascular techniques. The use of simulators could be an alternative educational tool, but some of them are cumbersome, expensive to implement, or lacking in realism. The aim of this study is to evaluate a reusable low-cost 3-dimensional printed training model we developed for aneurysm clipping. METHODS: The simulator was designed to replicate the bone structure, arteries, and targeted aneurysms. Thirty-two neurosurgery residents performed a craniotomy and aneurysm clipping using the model and then filled out a survey. They were divided into Junior and Senior groups. Descriptive, exploratory, and confirmatory factor analysis was performed using IBM SPSS statistical software. RESULTS: The overall residents' response was positive, with high scores to face validity and content validity questions. There was no significant statistical difference between the Junior and Senior groups. The confirmatory factor and internal consistency analysis confirmed that the evaluation was highly reliable. Globally, 97% of the residents found the model was useful and would repeat the simulator experience. The financial cost is $2500 USD for implementation and only $180 USD if further training sessions are required. CONCLUSIONS: The main strengths of our training model are its highlighted realism, adaptability to trainees of different levels of expertise, sustainability, and low cost. Our data support the concept that it can be incorporated as a new training opportunity during professional specialty meetings and/or within residency academic programs.

Apathy, Executive Function, and Emotion Recognition Are the Main Drivers of Functional Impairment in Behavioral Variant of Frontotemporal Dementia.

Background: The cognitive and neuropsychiatric deficits present in patients with behavioral variant frontotemporal dementia (bvFTD) are associated with loss of functionality in the activities of daily living (ADLs). The main purpose of this study was to examine and explore the association between the cognitive and neuropsychiatric features that might prompt functional impairment of basic, instrumental, and advanced ADL domains in patients with bvFTD. Methods: A retrospective cross-sectional study was conducted with 27 patients with bvFTD in its early stage (<2 years of evolution) and 32 healthy control subjects. A neuropsychological assessment was carried out wherein measures of cognitive function and neuropsychiatric symptoms were obtained. The informant-report Technology-Activities of Daily Living Questionnaire was used to assess the percentage of functional impairment in the different ADL domains. To identify the best determinants, three separate multiple regression analyses were performed, considering each functional impairment as the dependent variable and executive function, emotion recognition, disinhibition, and apathy as independent variables. Results: For the basic ADLs, a model that explains 28.2% of the variability was found, in which the presence of apathy (ß = 0.33, p = 0.02) and disinhibition (ß = 0.29, p = 0.04) were significant factors. Concerning instrumental ADLs, the model produced accounted for 63.7% of the functional variability, with the presence of apathy (ß = 0.71, p < 0.001), deficits in executive function (ß = -0.36, p = 0.002), and lack of emotion recognition (ß = 0.28, p = 0.017) as the main contributors. Finally, in terms of advanced ADLs, the model found explained 52.6% of the variance, wherein only the presence of apathy acted as a significant factor (ß = 0.59, p < 0.001). Conclusions: The results of this study show the prominent and transverse effect of apathy in the loss of functionality throughout all the ADL domains. Apart from that, this is the first study that shows that the factors associated with loss of functionality differ according to the functional domain in patients with bvFTD in its early stage. Finally, no other study has analyzed the impact of the lack of emotion recognition in the functionality of ADLs. These results could guide the planning of tailored interventions that might enhance everyday activities and the improvement of quality of life.

Análisis preliminar del efecto de la edad y la escolaridad en adultos sanos en el rendimiento del Sydney Language Battery (Sydbat) en español de Chile / Preliminary analysis of the effect of age and education in healthy adults on the performance of the Sydney Language Battery (Sydbat) in Chilean Spanish

Existen 3 variantes de afasia progresiva primaria (APP), que se distinguen según el dominio lingüístico predominantemente alterado: no fluente, logopénica y semántica. Una herramienta que ayuda a su clasificación es el Sydney Language Battery (Sydbat), el cual no se encuentra validado en Chile. El objetivo del presente trabajo es analizar la posible relación entre edad, años de escolaridad y rendimiento obtenido en las subpruebas del Sydbat en adultos sanos. Participaron 38 adultos sanos a losque se les aplicó el test.El promedio de edad fue 56,8 años (DE = 8,3) y tenían una media de 13,8 años de escolaridad (DE = 3,9). Todos provenían de la Región Metropolitana. Se realizaron correlaciones de Pearson y Spearman, para explorar la correlación entre el rendimiento en las subpruebas, la edad y la escolaridad. Considerando la variabilidad en el rendimiento en las subpruebas, se realizaron modelos uni y multivariados. Se encontraron correlaciones significativas entre edad y la subprueba comprensión (p<0,05) y los años de escolaridad con las subpruebas asociación semántica (p<0,001) y nominación (p<0,01). En personas con más de 12 años de escolaridad, el puntaje en la subprueba asociación semántica varió aproximadamente 2 puntos, con respecto a personas con menos de 12 años de escolaridad (p<0,01). Se concluye que las variaciones en el rendimiento del test, dependen la edad y la escolaridad. A mayor edad, menor es el rendimiento en la subprueba de comprensión. A mayor escolaridad, mayor es el rendimiento en las subpruebas de asociación semántica y nominación. El efecto mencionado debe ser considerado en el proceso de validación de Sydbat.

There are 3 variants of primary progressive aphasia (APP), which are distinguished according to the predominantly altered linguistic domain: non-fluent, logopenic, and semantic. A tool that helps in its classification is the Sydney Language Battery (Sydbat), which is not validated in Chile. The objective of this work is to analyze the possible relationship between age, years of schooling and performance obtained in the Sydbat subtests in healthy adults. 38 healthy adults participated in the test. The average age was 56.8 years (SD = 8.3) and they had a mean of 13.8 years of schooling (SD = 3.9). They all came from the Metropolitan Region. Pearson and Spearman correlations were performed to explore the correlation between subtest performance, age, and schooling. Considering the variability in performance in the subtests, univariate and multivariate models were performed. Significant correlations were found between age and the comprehension subtest (p <0.05) and the years of schooling with the semantic association (p <0.001) and nomination (p <0.01) subtests. In participants with more than 12 years of schooling, the score in the semantic association subtest varied approximately 2 points, with respect to people with less than 12 years of schooling (p <0.01). It is concluded that the variations in test performance depend on age andeducation. The older participants are, the lower their performance on the comprehension subtest. The higher the schooling, the higher the performance on the semantic association and nomination subtests. The mentioned effect must be considered in the Sydbat validation process.

Sensibilidad y especificidad del Test ScreeLing en usuarios afásicos en etapa aguda: un análisis preliminar / Sensitivity and Specificity of the Spanish version of the ScreeLing Test in aphasic patients at the acute phase: a pilot study

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.

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% andspecificity 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 differentlanguage severity profiles.

Alzheimer's Disease or Behavioral Variant Frontotemporal Dementia? Review of Key Points Toward an Accurate Clinical and Neuropsychological Diagnosis.

Alzheimer's disease (AD) and frontotemporal dementia (FTD) are the most common neurodegenerative early-onset dementias. Despite the fact that both conditions have a very distinctive clinical pattern, they present with an overlap in their cognitive and behavioral features that may lead to misdiagnosis or delay in diagnosis. The current review intends to summarize briefly the main differences at the clinical, neuropsychological, and behavioral levels, in an attempt to suggest which aspects would facilitate an adequate diagnosis in a clinical setting, especially in Latin American and low- and middle-income countries, where the resources needed for a differential diagnosis (such as MRI or biomarkers) are not always available. A timely diagnosis of AD and FTD have significant implications for the medical management and quality of life of patients and careers.

Early-stage differentiation between presenile Alzheimer's disease and frontotemporal dementia using arterial spin labeling MRI.

OBJECTIVE: To investigate arterial spin labeling (ASL)-MRI for the early diagnosis of and differentiation between the two most common types of presenile dementia: Alzheimer's disease (AD) and frontotemporal dementia (FTD), and for distinguishing age-related from pathological perfusion changes. METHODS: Thirteen AD and 19 FTD patients, and 25 age-matched older and 22 younger controls underwent 3D pseudo-continuous ASL-MRI at 3 T. Gray matter (GM) volume and cerebral blood flow (CBF), corrected for partial volume effects, were quantified in the entire supratentorial cortex and in 10 GM regions. Sensitivity, specificity and diagnostic performance were evaluated in regions showing significant CBF differences between patient groups or between patients and older controls. RESULTS: AD compared with FTD patients had hypoperfusion in the posterior cingulate cortex, differentiating these with a diagnostic performance of 74 %. Compared to older controls, FTD patients showed hypoperfusion in the anterior cingulate cortex, whereas AD patients showed a more widespread regional hypoperfusion as well as atrophy. Regional atrophy was not different between AD and FTD. Diagnostic performance of ASL to differentiate AD or FTD from controls was good (78-85 %). Older controls showed global hypoperfusion compared to young controls. CONCLUSION: ASL-MRI contributes to early diagnosis of and differentiation between presenile AD and FTD. KEY POINTS: ASL-MRI facilitates differentiation of early Alzheimer's disease and frontotemporal dementia. Posterior cingulate perfusion is lower in Alzheimer's disease than frontotemporal dementia. Compared to controls, Alzheimer's disease patients show hypoperfusion in multiple regions. Compared to controls, frontotemporal dementia patients show focal anterior cingulate hypoperfusion. Global decreased perfusion in older adults differs from hypoperfusion in dementia.

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.

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.