A simple and objective method for reproducible resting state network (RSN) detection in fMRI

Spatial Independent Component Analysis (ICA) decomposes the time by space functional MRI (fMRI) matrix into a set of 1-D basis time courses and their associated 3-D spatial maps that are optimized for mutual independence. When applied to resting state fMRI (rsfMRI), ICA produces several spatial independent components (ICs) that seem to have biological relevance - the so-called resting state networks (RSNs). The ICA problem is well posed when the true data generating process follows a linear mixture of ICs model in terms of the identifiability of the mixing matrix. However, the contrast function used for promoting mutual independence in ICA is dependent on the finite amount of observed data and is potentially non-convex with multiple local minima. Hence, each run of ICA could produce potentially different IC estimates even for the same data. One technique to deal with this run-to-run variability of ICA was proposed by Yang et al. (2008) in their algorithm RAICAR which allows for the selection of only those ICs that have a high run-to-run reproducibility. We propose an enhancement to the original RAICAR algorithm that enables us to assign reproducibility p-values to each IC and allows for an objective assessment of both within subject and across subjects reproducibility. We call the resulting algorithm RAICAR-N (N stands for null hypothesis test), and we have applied it to publicly available human rsfMRI data (http://www.nitrc.org). Our reproducibility analyses indicated that many of the published RSNs in rsfMRI literature are highly reproducible. However, we found several other RSNs that are highly reproducible but not frequently listed in the literature.Comment: 54 pages, 13 figure

SMART: A statistical framework for optimal design matrix generation with application to fMRI

The general linear model (GLM) is a well established tool for analyzing functional magnetic resonance imaging (fMRI) data. Most fMRI analyses via GLM proceed in a massively univariate fashion where the same design matrix is used for analyzing data from each voxel. A major limitation of this approach is the locally varying nature of signals of interest as well as associated confounds. This local variability results in a potentially large bias and uncontrolled increase in variance for the contrast of interest. The main contributions of this paper are two fold (1) We develop a statistical framework called SMART that enables estimation of an optimal design matrix while explicitly controlling the bias variance decomposition over a set of potential design matrices and (2) We develop and validate a numerical algorithm for computing optimal design matrices for general fMRI data sets. The implications of this framework include the ability to match optimally the magnitude of underlying signals to their true magnitudes while also matching the "null" signals to zero size thereby optimizing both the sensitivity and specificity of signal detection. By enabling the capture of multiple profiles of interest using a single contrast (as opposed to an F-test) in a way that optimizes for both bias and variance enables the passing of first level parameter estimates and their variances to the higher level for group analysis which is not possible using F-tests. We demonstrate the application of this approach to in vivo pharmacological fMRI data capturing the acute response to a drug infusion, to task-evoked, block design fMRI and to the estimation of a haemodynamic response function (HRF) response in event-related fMRI. Our framework is quite general and has potentially wide applicability to a variety of disciplines.Comment: 68 pages, 34 figure

A Key Role of the Basal Ganglia in Pain and Analgesia - Insights Gained Through Human Functional Imaging

The basal ganglia (BG) are composed of several nuclei involved in neural processing related to the execution of motor, cognitive and emotional activities. Preclinical and clinical data have implicated a role for these structures in pain processing. Recently neuroimaging has added important information on BG activation in conditions of acute pain, chronic pain and as a result of drug effects. Our current understanding of alterations in cortical and sub-cortical regions in pain suggests that the BG are uniquely involved in thalamo-cortico-BG loops to integrate many aspects of pain. These include the integration of motor, emotional, autonomic and cognitive responses to pain

An Approach to Localizing Corneal Pain Representation in Human Primary Somatosensory Cortex

The cornea has been a focus of animal electrophysiological research for decades, but little is known regarding its cortical representation in the human brain. This study attempts to localize the somatotopic representation of the cornea to painful stimuli in human primary somatosensory cortex using functional magnetic resonance imaging (fMRI). In this case study, a subject was imaged at 3T while bright light was presented in a block-design, which either produced pain and blinking (during photophobia) or blinking alone (after recovery from photophobia). Pain and blinking produced precisely localized activations in primary somatosensory cortex and primary motor cortex. These results indicate that noxious stimulation of the cornea can produce somatotopic activation in primary somatosensory cortex. This finding opens future avenues of research to evaluate the relationship between corneal pain and central brain mechanisms relating to the development of chronic pain conditions, such as dry eye-like symptoms

Altered Hypothalamic Functional Connectivity with Autonomic Circuits and the Locus Coeruleus in Migraine

The hypothalamus has been implicated in migraine based on the manifestation of autonomic symptoms with the disease, as well as neuroimaging evidence of hypothalamic activation during attacks. Our objective was to determine functional connectivity (FC) changes between the hypothalamus and the rest of the brain in migraine patients vs. control subjects. This study uses fMRI (functional magnetic resonance imaging) to acquire resting state scans in 12 interictal migraine patients and 12 healthy matched controls. Hypothalamic connectivity seeds were anatomically defined based on high-resolution structural scans, and FC was assessed in the resting state scans. Migraine patients had increased hypothalamic FC with a number of brain regions involved in regulation of autonomic functions, including the locus coeruleus, caudate, parahippocampal gyrus, cerebellum, and the temporal pole. Stronger functional connections between the hypothalamus and brain areas that regulate sympathetic and parasympathetic functions may explain some of the hypothalamic-mediated autonomic symptoms that accompany or precede migraine attacks

Nivel de conocimientos sobre anemia ferropénica en cuidadores de niños de 6 a 36 meses de edad en Lima-Perú

El objetivo de este trabajo de investigación es evaluar el nivel de conocimientos sobre anemia ferropénica en los cuidadores de niños de 6 a 36 meses de edad que acude al centro de salud Chacarilla de Otero. Lima - Perú. El estudio con enfoque cuantitativo, no experimental, observacional con diseño descriptivo y de corte transversal, tuvo como muestra a 132 cuidadores de niños de 6 a 36 meses de edad. El instrumento que se utilizó para la recolección de información fue el cuestionario sobre anemia ferropénica. Los resultados indicaron, del total de cuidadores encuestados (132) sobre el nivel de conocimientos sobre anemia ferropénica, 9.1% (n=12) obtuvo un nivel de conocimiento bajo, 50% (n=66) obtuvo un nivel de conocimiento medio y 40.9% (n=54) obtuvo un nivel de conocimiento alto. Se concluye que el nivel de conocimiento que más predominó en los cuidadores encuestados fue el nivel medio (50%), además se observó que la dimensión con menor nivel de conocimiento fue los alimentos fuentes y hierro ya que la mayoría de ellos tuvo un nivel de conocimiento bajo (45.5%).The objective of this research work is to evaluate the level of knowledge about iron deficiency anemia in caregivers of children from 6 to 36 months of age who attend the Chacarilla de Otero health center. Lima Peru. The study with a quantitative, non-experimental, observational approach with a descriptive and cross-sectional design, had as a sample 132 caregivers of children from 6 to 36 months of age. The instrument used to collect information was the iron deficiency anemia questionnaire. The results indicated, of the total number of caregivers surveyed (132) about the level of knowledge about iron deficiency anemia, 9.1% (n=12) obtained a low level of knowledge, 50% (n=66) obtained a medium level of knowledge and 40.9 % (n=54) obtained a high level of knowledge. It is concluded that the level of knowledge that most predominated in the caregivers surveyed was the medium level (50%), in addition it was observed that the dimension with the lowest level of knowledge was food sources and iron since most of them had a level of low knowledge (45.5%)ChosicaEstrategias en Salud pública en alimentación y nutriciónEscuela Profesional de Nutrición Human

Yohimbine-Induced Amygdala Activation in Pathological Gamblers: A Pilot Study

Rationale and Objectives: There is evidence that drug addiction is associated with increased physiological and psychological responses to stress. In this pilot functional magnetic resonance imaging (fMRI) study we assessed whether a prototype behavioral addiction, pathological gambling (PG), is likewise associated with an enhanced response to stress. Methods: We induced stress by injecting yohimbine (0.2–0.3 mg/kg, IV), an alpha-2 adrenoceptor antagonist that elicits stress-like physiological and psychological effects in humans and in laboratory animals, to four subjects with PG and to five non-gamblers mentally healthy control subjects. Their fMRI brain responses were assessed along with subjective stress and gambling urges ratings. Results: Voxelwise analyses of data sets from individual subjects, utilizing generalized linear model approach, revealed significant left amygdala activation in response to yohimbine across all PG subjects. This amygdala effect was not observed in the five control individuals. Yohimbine elicited subjective stress ratings in both groups with greater (albeit not statically significantly) average response in the PG subjects. On the other hand, yohimbine did not induce urges to gamble

Transient and Persistent Pain Induced Connectivity Alterations in Pediatric Complex Regional Pain Syndrome

Evaluation of pain-induced changes in functional connectivity was performed in pediatric complex regional pain syndrome (CRPS) patients. High field functional magnetic resonance imaging was done in the symptomatic painful state and at follow up in the asymptomatic pain free/recovered state. Two types of connectivity alterations were defined: (1) Transient increases in functional connectivity that identified regions with increased cold-induced functional connectivity in the affected limb vs. unaffected limb in the CRPS state, but with normalized connectivity patterns in the recovered state; and (2) Persistent increases in functional connectivity that identified regions with increased cold-induced functional connectivity in the affected limb as compared to the unaffected limb that persisted also in the recovered state (recovered affected limb versus recovered unaffected limb). The data support the notion that even after symptomatic recovery, alterations in brain systems persist, particularly in amygdala and basal ganglia systems. Connectivity analysis may provide a measure of temporal normalization of different circuits/regions when evaluating therapeutic interventions for this condition. The results add emphasis to the importance of early recognition and management in improving outcome of pediatric CRPS

Diffuse Optical Tomography Activation in the Somatosensory Cortex: Specific Activation by Painful vs. Non-Painful Thermal Stimuli

Background: Pain is difficult to assess due to the subjective nature of self-reporting. The lack of objective measures of pain has hampered the development of new treatments as well as the evaluation of current ones. Functional MRI studies of pain have begun to delineate potential brain response signatures that could be used as objective read-outs of pain. Using Diffuse Optical Tomography (DOT), we have shown in the past a distinct DOT signal over the somatosensory cortex to a noxious heat stimulus that could be distinguished from the signal elicited by innocuous mechanical stimuli. Here we further our findings by studying the response to thermal innocuous and noxious stimuli. Methodology/Principal Findings: Innocuous and noxious thermal stimuli were applied to the skin of the face of the first division (ophthalmic) of the trigeminal nerve in healthy volunteers (N = 6). Stimuli temperatures were adjusted for each subject to evoke warm (equivalent to a 3/10) and painful hot (7/10) sensations in a verbal rating scale (0/10 = no/max pain). A set of 26 stimuli (5 sec each) was applied for each temperature with inter-stimulus intervals varied between 8 and 15 sec using a Peltier thermode. A DOT system was used to capture cortical responses on both sides of the head over the primary somatosensory cortical region (S1). For the innocuous stimuli, group results indicated mainly activation on the contralateral side with a weak ipsilateral response. For the noxious stimuli, bilateral activation was observed with comparable amplitudes on both sides. Furthermore, noxious stimuli produced a temporal biphasic response while innocuous stimuli produced a monophasic response. Conclusions/Significance: These results are in accordance with fMRI and our other DOT studies of innocuous mechanical and noxious heat stimuli. The data indicate the differentiation of DOT cortical responses for pain vs. innocuous stimuli that may be useful in assessing objectively acute pain

Resting-State Functional Connectivity in the Infant Brain: Methods, Pitfalls, and Potentiality

Early brain development is characterized by rapid growth and perpetual reconfiguration, driven by a dynamic milieu of heterogeneous processes. Postnatal brain plasticity is associated with increased vulnerability to environmental stimuli. However, little is known regarding the ontogeny and temporal manifestations of inter- and intra-regional functional connectivity that comprise functional brain networks. Resting-state functional magnetic resonance imaging (rs-fMRI) has emerged as a promising non-invasive neuroinvestigative tool, measuring spontaneous fluctuations in blood oxygen level dependent (BOLD) signal at rest that reflect baseline neuronal activity. Over the past decade, its application has expanded to infant populations providing unprecedented insight into functional organization of the developing brain, as well as early biomarkers of abnormal states. However, many methodological issues of rs-fMRI analysis need to be resolved prior to standardization of the technique to infant populations. As a primary goal, this methodological manuscript will (1) present a robust methodological protocol to extract and assess resting-state networks in early infancy using independent component analysis (ICA), such that investigators without previous knowledge in the field can implement the analysis and reliably obtain viable results consistent with previous literature; (2) review the current methodological challenges and ethical considerations associated with emerging field of infant rs-fMRI analysis; and (3) discuss the significance of rs-fMRI application in infants for future investigations of neurodevelopment in the context of early life stressors and pathological processes. The overarching goal is to catalyze efforts toward development of robust, infant-specific acquisition, and preprocessing pipelines, as well as promote greater transparency by researchers regarding methods used