A real-time fMRI neurofeedback system for the clinical alleviation of depression with a subject-independent classification of brain states: A proof of principle study.

Most clinical neurofeedback studies based on functional magnetic resonance imaging use the patient's own neural activity as feedback. The objective of this study was to create a subject-independent brain state classifier as part of a real-time fMRI neurofeedback (rt-fMRI NF) system that can guide patients with depression in achieving a healthy brain state, and then to examine subsequent clinical changes. In a first step, a brain classifier based on a support vector machine (SVM) was trained from the neural information of happy autobiographical imagery and motor imagery blocks received from a healthy female participant during an MRI session. In the second step, 7 right-handed female patients with mild or moderate depressive symptoms were trained to match their own neural activity with the neural activity corresponding to the "happiness emotional brain state" of the healthy participant. The training (4 training sessions over 2 weeks) was carried out using the rt-fMRI NF system guided by the brain-state classifier we had created. Thus, the informative voxels previously obtained in the first step, using SVM classification and Effect Mapping, were used to classify the Blood-Oxygen-Level Dependent (BOLD) activity of the patients and converted into real-time visual feedback during the neurofeedback training runs. Improvements in the classifier accuracy toward the end of the training were observed in all the patients [Session 4-1 Median = 6.563%; Range = 4.10-27.34; Wilcoxon Test (0), 2-tailed p = 0.031]. Clinical improvement also was observed in a blind standardized clinical evaluation [HDRS CE2-1 Median = 7; Range 2 to 15; Wilcoxon Test (0), 2-tailed p = 0.016], and in self-report assessments [BDI-II CE2-1 Median = 8; Range 1-15; Wilcoxon Test (0), 2-tailed p = 0.031]. In addition, the clinical improvement was still present 10 days after the intervention [BDI-II CE3-2_Median = 0; Range -1 to 2; Wilcoxon Test (0), 2-tailed p = 0.50/ HDRS CE3-2 Median = 0; Range -1 to 2; Wilcoxon Test (0), 2-tailed p = 0.625]. Although the number of participants needs to be increased and a control group included to confirm these findings, the results suggest a novel option for neural modulation and clinical alleviation in depression using noninvasive stimulation technologies.

M-CHAT-R/F Validation as a screening tool for early detection in children with autism spectrum disorder. / Validación del M-CHAT-R/F como instrumento de tamizaje para detección precoz en niños con trastorno del espectro autista.

INTRODUCTION: Screening for Autism Spectrum Disorders (ASD) using the Modified Checklist for Autism in Toddlers, Revised with Follow-up (M-CHAT-R/F) increases early detection, allowing early interventions and improving prognosis. This tool is part of the management in case of suspected ASD in several clinical guidelines. The objective of this article was to conduct the concurrent and discrimi nant validation and the reliability analysis of M-CHAT-R/F in the Chilean population. PATIENTS AND METHOD: This is the second stage of the cross-cultural adaptation of cross-sectional design. M-CHAT- R/F was applied to a sample of 20 children with suspected ASD and 100 randomly selected healthy control children, aged between 16-30 months. Autism Diagnostic Observation Schedule (ADOS-2), considered as reference, was applied to the 20 patients of the clinical sample, to 20 children of the healthy control sample and to those cases of the healthy control sample with M-CHAT-R/F positive. Cronbach alpha was calculated, as well as M-CHAT-R/F and ADOS-2 correlation, sensitivity, and specificity analyses. RESULTS: In the healthy sample, M-CHAT-R/F was positive in two patients, with one of them positive and the other one negative for ASD with ADOS-2 test. In the clinical sample, M- CHAT-R/F was positive in all cases, three of them were negative in the ADOS-2 test. The Alfa relia bility of M-CHART-R/T was 0,889, the discriminant sensitivity and specificity were 100% and 98%, and the concurrent ones were 100% and 87.5% respectively. CONCLUSIONS: The Chilean M-CHAT- R/F version was reliable, sensitive and specific, similar to the original test, which opens the possibility for its use in clinical samples and for research. Validating M-CHAT-R/F is an ongoing process which must be further developed.

Validación del M-CHAT-R/F como instrumento de tamizaje para detección precoz en niños con trastorno del espectro autista / M-CHAT-R/F validation as a screening tool for early detection in children with autism spectrum disorder

INTRODUCCIÓN: El tamizaje de los Trastornos del Espectro Autista (TEA) mediante el Modified Chec klist for Autism in Toddlers - Revised with Follow Up (M-CHAT-R/F) aumenta la detección precoz, posibilitando intervenciones tempranas y mejorando el pronóstico. Este instrumento es parte del algoritmo de manejo ante la sospecha de TEA en diversas guías clínicas. El objetivo fue realizar la validación concurrente, discriminante y el análisis de confiabilidad del M-CHAT-R/F en una pobla ción chilena. PACIENTES Y MÉTODO: Esta es la segunda etapa de la adaptación transcultural, de diseño transversal. Se aplicó M-CHAT-R/F a una muestra de 20 niños con sospecha de TEA y 100 niños de control sano seleccionados al azar, de 16-30 meses de edad. Se aplicó Autism Diagnostic Observation Schedule (ADOS-2), considerado como referencia, a los 20 pacientes de la muestra clínica, a 20 niños de la muestra de control sano y a aquellos casos de la muestra de control sano con M-CHAT-R/F po sitivo. Se calculó alfa de Cronbach, análisis de correlación de M-CHAT-R/F y ADOS-2 y sensibilidad y especificidad. RESULTADOS: En el grupo de control sano, M-CHAT-R/F resultó alterado en 2 pacien tes, siendo uno positivo y otro negativo para TEA con ADOS-2. En muestra clínica el M-CHAT-R/F fue positivo en todos, con test de ADOS-2 negativo en 3 casos. La confiabilidad Alfa del M-CHAT- R/F fue =0,889, la sensibilidad y especificidad discriminante de 100 y 98% y la concurrente 100% y 87,5% respectivamente. CONCLUSIÓN: M-CHAT-R/F en su versión chilena resultó fiable, sensible y específico de manera similar al original, lo cual abre la posibilidad de su utilización en población clínica y para investigación. La validación es un proceso continuo que se debe profundizar.

INTRODUCTION: Screening for Autism Spectrum Disorders (ASD) using the Modified Checklist for Autism in Toddlers, Revised with Follow-up (M-CHAT-R/F) increases early detection, allowing early interventions and improving prognosis. This tool is part of the management in case of suspected ASD in several clinical guidelines. The objective of this article was to conduct the concurrent and discrimi nant validation and the reliability analysis of M-CHAT-R/F in the Chilean population. PATIENTS AND METHOD: This is the second stage of the cross-cultural adaptation of cross-sectional design. M-CHAT- R/F was applied to a sample of 20 children with suspected ASD and 100 randomly selected healthy control children, aged between 16-30 months. Autism Diagnostic Observation Schedule (ADOS-2), considered as reference, was applied to the 20 patients of the clinical sample, to 20 children of the healthy control sample and to those cases of the healthy control sample with M-CHAT-R/F positive. Cronbach alpha was calculated, as well as M-CHAT-R/F and ADOS-2 correlation, sensitivity, and specificity analyses. RESULTS: In the healthy sample, M-CHAT-R/F was positive in two patients, with one of them positive and the other one negative for ASD with ADOS-2 test. In the clinical sample, M- CHAT-R/F was positive in all cases, three of them were negative in the ADOS-2 test. The Alfa relia bility of M-CHART-R/T was 0,889, the discriminant sensitivity and specificity were 100% and 98%, and the concurrent ones were 100% and 87.5% respectively. CONCLUSIONS: The Chilean M-CHAT- R/F version was reliable, sensitive and specific, similar to the original test, which opens the possibility for its use in clinical samples and for research. Validating M-CHAT-R/F is an ongoing process which must be further developed.

Self-Regulation of the Fusiform Face Area in Autism Spectrum: A Feasibility Study With Real-Time fMRI Neurofeedback.

One of the most important and early impairments in autism spectrum disorder (ASD) is the abnormal visual processing of human faces. This deficit has been associated with hypoactivation of the fusiform face area (FFA), one of the main hubs of the face-processing network. Neurofeedback based on real-time fMRI (rtfMRI-NF) is a technique that allows the self-regulation of circumscribed brain regions, leading to specific neural modulation and behavioral changes. The aim of the present study was to train participants with ASD to achieve up-regulation of the FFA using rtfMRI-NF, to investigate the neural effects of FFA up-regulation in ASD. For this purpose, three groups of volunteers with normal I.Q. and fluent language were recruited to participate in a rtfMRI-NF protocol of eight training runs in 2 days. Five subjects with ASD participated as part of the experimental group and received contingent feedback to up-regulate bilateral FFA. Two control groups, each one with three participants with typical development (TD), underwent the same protocol: one group with contingent feedback and the other with sham feedback. Whole-brain and functional connectivity analysis using each fusiform gyrus as independent seeds were carried out. The results show that individuals with TD and ASD can achieve FFA up-regulation with contingent feedback. RtfMRI-NF in ASD produced more numerous and stronger short-range connections among brain areas of the ventral visual stream and an absence of the long-range connections to insula and inferior frontal gyrus, as observed in TD subjects. Recruitment of inferior frontal gyrus was observed in both groups during FAA up-regulation. However, insula and caudate nucleus were only recruited in subjects with TD. These results could be explained from a neurodevelopment perspective as a lack of the normal specialization of visual processing areas, and a compensatory mechanism to process visual information of faces. RtfMRI-NF emerges as a potential tool to study visual processing network in ASD, and to explore its clinical potential.