Conectividad funcional a partir de la perfusión cerebral en pacientes epilépticos y con enfermedad de Parkinson / Functional connectivity from cerebral perfusion in patients with epilepsy and Parkinson's disease

Introducción: La epilepsia y la enfermedad de Parkinson han sido descritos como trastornos de redes neurales. El estudio de la conectividad por modalidades moleculares puede ser más relevante fisiológicamente que los basados en señales hemodinámicas. Objetivo: Proponer una metodología para la descripción de patrones de conectividad funcional a partir de la perfusión cerebral por tomografía por emisión de fotón único. Métodos: La metodología incluye cuatro pasos principales: preprocesamiento espacial, corrección del volumen parcial, cálculo del índice de perfusión y obtención de la matriz de conectividad funcional mediante el coeficiente de correlación de Pearson. Se implementó en 25 pacientes con distintos trastornos neurológicos: 15 con epilepsia farmacorresistente y 10 con enfermedad de Parkinson. Resultados: Se encontraron diferencias significativas entre los índice de perfusión de varias regiones de los hemisferios ipsilateral y contralateral tanto en pacientes con epilepsia del lóbulo frontal como en pacientes con epilepsia del lóbulo temporal. Igual resultado se obtuvo en los pacientes con enfermedad de Parkinson con distintos estadios de la enfermedad. Para cada grupo se identificaron patrones de conectividad funcional que involucran a regiones relacionadas con la patología en estudio. Conclusiones: Con el desarrollo de esta metodología se ha demostrado que la tomografía por emisión de fotón único aporta información valiosa para estudiar la organización de las redes funcionales del cerebro. Futuras investigaciones con mayor número de pacientes contribuirían a hacer inferencias sobre los correlatos neurales de los distintos trastornos cerebrales(AU)

Introduction: Epilepsy and Parkinson's disease have been described as disorders of neural networks. The study of connectivity by molecular modalities may be more physiologically relevant than those based on hemodynamic signals. Aim: The aim of the present work is to propose a methodology for the description of functional connectivity patterns from brain perfusion by single photon emission tomography. Methods: The methodology includes four main steps: spatial preprocessing, partial volume correction, calculation of the perfusion index and obtaining the functional connectivity matrix using Pearson's correlation coefficient. It was implemented in 25 patients with different neurological disorders: 15 with drug-resistant epilepsy and 10 suffering Parkinson's disease. Results: Significant differences were found between the perfusion indexes of various regions of the ipsilateral and contralateral hemispheres in both patients with frontal lobe epilepsy and patients with temporal lobe epilepsy. The same result was obtained in Parkinson's disease patients with different stages of the disease. For each group, functional connectivity patterns involving regions related to the pathology under study were identified. Conclusions: With the development of this methodology, it has been demonstrated that single photon emission tomography provides valuable information to study the organization of functional brain networks. Future research with a larger number of patients would contribute to make inferences about the neural correlates of the different brain disorders(AU)

A guide for the use of fNIRS in microcephaly associated to congenital Zika virus infection.

Congenital Zika Syndrome (CZS) is characterized by changes in cranial morphology associated with heterogeneous neurological manifestations and cognitive and behavioral impairments. In this syndrome, longitudinal neuroimaging could help clinicians to predict developmental trajectories of children and tailor treatment plans accordingly. However, regularly acquiring magnetic resonance imaging (MRI) has several shortcomings besides cost, particularly those associated with childrens' clinical presentation as sensitivity to environmental stimuli. The indirect monitoring of local neural activity by non-invasive functional near-infrared spectroscopy (fNIRS) technique can be a useful alternative for longitudinally accessing the brain function in children with CZS. In order to provide a common framework for advancing longitudinal neuroimaging assessment, we propose a principled guideline for fNIRS acquisition and analyses in children with neurodevelopmental disorders. Based on our experience on collecting fNIRS data in children with CZS we emphasize the methodological challenges, such as clinical characteristics of the sample, desensitization, movement artifacts and environment control, as well as suggestions for tackling such challenges. Finally, metrics based on fNIRS can be associated with established clinical metrics, thereby opening possibilities for exploring this tool as a long-term predictor when assessing the effectiveness of treatments aimed at children with severe neurodevelopmental disorders.

Cerebral Structure and Function in Stroke-free Patients with Atrial Fibrillation.

OBJECTIVES: Atrial fibrillation (AF) is associated with high risk of dementia and brain atrophy in stroke-free patients, but the mechanisms underlying this association remain unclear. We aimed to examine the brain volume and connectivity of paramount cognitive brain networks in stroke-free patients with AF without dementia. MATERIALS AND METHODS: Twenty-six stroke-free patients with AF and 26 age and sex-matched subjects without AF were submitted to a 3-tesla brain structural and functional MRI. An extensive clinical evaluation excluded stroke, dementia, low cardiac output, carotid stenosis and metabolic diseases without optimal therapy. We used CHA2DS2-VASc score to classify the cardiovascular risk factor burden and a broad neuropsychological battery to assess the cognitive performance. Voxel based morphometry analysis of. structural MRI defined whole-brain gray and white matter volumes. Finally, we used eco-plannar MRI images to compare the differences of functional connectivity of 7 large-scale resting-state networks between AF patients and controls. RESULTS: Taking into account the history of hypertension and heart failure, AF was associated to volume decrease of the right basal frontal lobe and right inferior cerebellum. Decreased connectivity of the ventral Default Mode Network (vDMN) was observed in the AF group. No disruption of connectivity was observed in the executive, visuospatial and salience networks. CONCLUSION: Individuals with AF without stroke or dementia have subtle reduction of gray and white matter, restricted to frontal areas and cerebellum. These patients show decreased vDMN connectivity, without other large-scale brain network disruption.

Aerobic Exercise Combined With Transcranial Direct Current Stimulation Over the Prefrontal Cortex in Parkinson Disease: Effects on Cortical Activity, Gait, and Cognition.

BACKGROUND: Since people with Parkinson disease (PD) rely on limited prefrontal executive resources for the control of gait, interventions targeting the prefrontal cortex (PFC) may help in managing PD-related gait impairments. Transcranial direct current stimulation (tDCS) can be used to modulate PFC excitability and improve prefrontal cognitive functions and gait. OBJECTIVE: We investigated the effects of adding anodal tDCS applied over the PFC to a session of aerobic exercise on gait, cognition, and PFC activity while walking in people with PD. METHODS: A total of 20 people with PD participated in this randomized, double-blinded, sham-controlled crossover study. Participants attended two 30-minute sessions of aerobic exercise (cycling at moderate intensity) combined with different tDCS conditions (active- or sham-tDCS), 1 week apart. The order of sessions was counterbalanced across the sample. Anodal tDCS (2 mA for 20 minutes [active-tDCS] or 10 s [sham-tDCS]) targeted the PFC in the most affected hemisphere. Spatiotemporal gait parameters, cognitive functions, and PFC activity while walking were assessed before and immediately after each session. RESULTS: Compared with the pre-assessment, participants decreased step time variability (effect size: -0.4), shortened simple and choice reaction times (effect sizes: -0.73 and -0.57, respectively), and increased PFC activity in the stimulated hemisphere while walking (effect size: 0.54) only after aerobic exercise + active-tDCS. CONCLUSION: The addition of anodal tDCS over the PFC to a session of aerobic exercise led to immediate positive effects on gait variability, processing speed, and executive control of walking in people with PD.

Motor Cortex Activation During Writing in Focal Upper-Limb Dystonia: An fNIRS Study.

BACKGROUND: Functional imaging studies have associated dystonia with abnormal activation in motor and sensory brain regions. Commonly used techniques such as functional magnetic resonance imaging impose physical constraints, limiting the experimental paradigms. Functional near-infrared spectroscopy (fNIRS) offers a new noninvasive possibility for investigating cortical areas and the neural correlates of complex motor behaviors in unconstrained settings. METHODS: We compared the cortical brain activation of patients with focal upper-limb dystonia and controls during the writing task under naturalistic conditions using fNIRS. The primary motor cortex (M1), the primary somatosensory cortex (S1), and the supplementary motor area were chosen as regions of interest (ROIs) to assess differences in changes in both oxyhemoglobin (oxy-Hb) and deoxyhemoglobin (deoxy-Hb) between groups. RESULTS: Group average activation maps revealed an expected pattern of contralateral recruitment of motor and somatosensory cortices in the control group and a more bilateral pattern of activation in the dystonia group. Between-group comparisons focused on specific ROIs revealed an increased activation of the contralateral M1 and S1 cortices and also of the ipsilateral M1 cortex in patients. CONCLUSIONS: Overactivity of contralateral M1 and S1 in dystonia suggest a reduced specificity of the task-related cortical areas, whereas ipsilateral activation possibly indicates a primary disorder of the motor cortex or an endophenotypic pattern. To our knowledge, this is the first study using fNIRS to assess cortical activity in dystonia during the writing task under natural settings, outlining the potential of this technique for monitoring sensory and motor retraining in dystonia rehabilitation.

Cognitive tasks as provocation methods in routine EEG: a multicentre field study.

This study aimed to analyse the effect of neuropsychological activation methods on interictal epileptiform discharges, compared to standard activation methods, for both focal and generalized epilepsies. This was a multicentre, prospective study including 429 consecutive EEG recordings of individuals with confirmed or suspected diagnosis of epilepsy. Neuropsychological activation included reading aloud in foreign and native language, praxis and a letter cancelation task (each with a duration of three minutes). After counting interictal discharges in three-minute time windows, activation and inhibition were assessed for each procedure, accounting for spontaneous fluctuations (95% CI) and compared to the baseline condition with eyes closed. Differences between generalized and focal epilepsies were explored. Interictal epileptiform discharges were present in 59.4% of the recordings. Activation was seen during hyperventilation in 31%, in at least one neuropsychological activation method in 15.4%), during intermittent photic simulation in 13.1% and in the resting condition with eyes open in 9.9%. The most frequent single cognitive task eliciting activation was praxis (10.3%). Lasting activation responses were found in 18-25%. Significant inhibition was found in 88/98 patients with baseline interictal epileptiform discharges, and was not task-specific. Adding a brief neuropsychological activation protocol to the standard EEG slightly increased its sensitivity in patients with either focal or generalized epilepsy. However, in unselected epilepsy patients, this effect seems only exceptionally to result in ultimate diagnostic gain, compared to standard procedures. From a diagnostic perspective, cognitive tasks should be reserved for patients with a suspicion of cognitive reflex epilepsy/seizures and probably require longer exposure times. Further research is needed to explore potential therapeutic applications of the observed inhibition of interictal epileptiform discharges by cognitive tasks in some patients.

Frontal Hemodynamic Response During Step Initiation Under Cognitive Conflict in Older and Young Healthy People.

Gait initiation is a daily challenge even for healthy individuals as it requires the timely coupling between the automatic anticipatory postural adjustment (APA) and the voluntary step according to the context. Modulation of this motor event has been thought to involve higher level brain control, including cognitive inhibitory circuitries. Despite the known participation of the supplementary motor area (SMA) in the modulation of some parameters of APA, the participation of areas controlling inhibition during gait initiation still needs to be investigated. In this study, the hemodynamic responses of the SMA and dorsolateral prefrontal cortex (DLPFC) were assessed using functional near-infrared spectroscopy (fNIRS) during a gait initiation task under cognitive conflict to select the foot to step (congruent [CON] and incongruent [INC] conditions). The older group (OG) showed worse inhibitory control than the young group (YG) along with more impairments in APA parameters. OG also had a lower amplitude of hemodynamic responses in both areas than YG in the INC. The INC increased the correlation between SMA and DLPFC only in the YG. Aging seems to impair the interaction between the hemodynamic responses of SMA and DLPFC, which influences APA performance in gait initiation under cognitive conflict.

Is Cortical Activation During Walking Different Between Parkinson's Disease Motor Subtypes?

Parkinson's disease (PD) is often classified into tremor dominant (TD) and postural instability gait disorder (PIGD) subtypes. Degeneration of subcortical/cortical pathways is different between PD subtypes, which leads to differences in motor behavior. However, the influence of PD subtype on cortical activity during walking remains poorly understood. Therefore, we aimed to investigate the influence of PD motor subtypes on cortical activity during unobstructed walking and obstacle avoidance. Seventeen PIGD and 19 TD patients performed unobstructed walking and obstacle avoidance conditions. Brain activity was measured using a mobile functional near-infrared spectroscopy-electroencephalography (EEG) systems, and gait parameters were analyzed using an electronic carpet. Concentrations of oxygenated hemoglobin (HbO2) of the prefrontal cortex (PFC) and EEG absolute power from alpha, beta, and gamma bands in FCz, Cz, CPz, and Oz channels were calculated. These EEG channels correspond to supplementary motor area, primary motor cortex, posterior parietal cortex, and visual cortex, respectively. Postural instability gait disorder patients presented higher PFC activity than TD patients, regardless of the walking condition. Tremor dominant patients presented reduced beta power in the Cz channel during obstacle avoidance compared to unobstructed walking. Both TD and PIGD patients decreased alpha and beta power in the FCz and CPz channels. In conclusion, PIGD patients need to recruit additional cognitive resources from the PFC for walking. Both TD and PIGD patients presented changes in the activation of brain areas related to motor/sensorimotor areas in order to maintain balance control during obstacle avoidance, being that TD patients presented further changes in the motor area (Cz channel) to avoid obstacles.

Dynamic brain fluctuations outperform connectivity measures and mirror pathophysiological profiles across dementia subtypes: A multicenter study.

From molecular mechanisms to global brain networks, atypical fluctuations are the hallmark of neurodegeneration. Yet, traditional fMRI research on resting-state networks (RSNs) has favored static and average connectivity methods, which by overlooking the fluctuation dynamics triggered by neurodegeneration, have yielded inconsistent results. The present multicenter study introduces a data-driven machine learning pipeline based on dynamic connectivity fluctuation analysis (DCFA) on RS-fMRI data from 300 participants belonging to three groups: behavioral variant frontotemporal dementia (bvFTD) patients, Alzheimer's disease (AD) patients, and healthy controls. We considered non-linear oscillatory patterns across combined and individual resting-state networks (RSNs), namely: the salience network (SN), mostly affected in bvFTD; the default mode network (DMN), mostly affected in AD; the executive network (EN), partially compromised in both conditions; the motor network (MN); and the visual network (VN). These RSNs were entered as features for dementia classification using a recent robust machine learning approach (a Bayesian hyperparameter tuned Gradient Boosting Machines (GBM) algorithm), across four independent datasets with different MR scanners and recording parameters. The machine learning classification accuracy analysis revealed a systematic and unique tailored architecture of RSN disruption. The classification accuracy ranking showed that the most affected networks for bvFTD were the SN + EN network pair (mean accuracy = 86.43%, AUC = 0.91, sensitivity = 86.45%, specificity = 87.54%); for AD, the DMN + EN network pair (mean accuracy = 86.63%, AUC = 0.89, sensitivity = 88.37%, specificity = 84.62%); and for the bvFTD vs. AD classification, the DMN + SN network pair (mean accuracy = 82.67%, AUC = 0.86, sensitivity = 81.27%, specificity = 83.01%). Moreover, the DFCA classification systematically outperformed canonical connectivity approaches (including both static and linear dynamic connectivity). Our findings suggest that non-linear dynamical fluctuations surpass two traditional seed-based functional connectivity approaches and provide a pathophysiological characterization of global brain networks in neurodegenerative conditions (AD and bvFTD) across multicenter data.

Cortical Brain Functions ­ The Brodmann Legacy in the 21st Century

In 1909, Korbinian Brodmann described 52 functional brain areas, 43 of them found in the human brain. More than a century later, his devoted functional map was incremented by Glasser et al in 2016, using functional nuclear magnetic resonance imaging techniques to propose the existence of 180 functional areas in each hemisphere, based on their cortical thickness, degree of myelination (cortical myelin content), neuronal interconnection, topographic organization, multitask answers, and assessment in their resting state. This opens a huge possibility, through functional neuroanatomy, to understand a little more about normal brain function and its functional impairment in the presence of a disease.

Prefrontal Cortex Activity During Walking: Effects of Aging and Associations With Gait and Executive Function.

BACKGROUND: Declines in gait parameters are common with aging and more pronounced in tasks with increased executive demand. However, the neural correlates of age-related gait impairments are not fully understood yet. OBJECTIVES: To investigate (a) the effects of aging on prefrontal cortex (PFC) activity and gait parameters during usual walking, obstacle crossing and dual-task walking and (b) the association between PFC activity and measures of gait and executive function. METHODS: Eighty-eight healthy individuals were distributed into 6 age-groups: 20-25 (G20), 30-35 (G30), 40-45 (G40), 50-55 (G50), 60-65 (G60), and 70-75 years (G70). Participants walked overground under 3 conditions: usual walking, obstacle crossing, and dual-task walking. Changes in oxygenated and deoxygenated hemoglobin in the PFC were recorded using functional near-infrared spectroscopy. Gait spatiotemporal parameters were assessed using an electronic walkway. Executive function was assessed through validated tests. RESULTS: Between-group differences on PFC activity were observed for all conditions. Multiple groups (ie, G30, G50, G60, and G70) showed increased PFC activity in at least one of the walking conditions. Young adults (G20 and G30) had the lowest levels of PFC activity while G60 had the highest levels. Only G70 showed reduced executive function and gait impairments (which were more pronounced during obstacle crossing and dual-task walking). PFC activity was related to gait and executive function. CONCLUSIONS: Aging causes a gradual increase in PFC activity during walking. This compensatory mechanism may reach the resource ceiling in the 70s, when reduced executive function limits its efficiency and gait impairments are observed.

Lisdexamfetamine Alters BOLD-fMRI Activations Induced by Odor Cues in Impulsive Children.

INTRODUCTION: Lisdexamfetamine (LDX) is a drug used to treat ADHD/impulsive patients. Impulsivity is known to affect inhibitory, emotional and cognitive function. On the other hand, smell and odor processing are known to be affected by neurological disorders, as they are modulators of addictive and impulsive behaviors specifically. We hypothesize that, after LDX ingestion, inhibitory pathways of the brain would change, and complementary behavioral regulation mechanisms would appear to regulate decision-making and impulsivity. METHODS: 20 children were studied in an aleatory crossover study. Imaging of BOLD-fMRI activity, elicited by olfactory stimulation in impulsive children, was performed after either LDX or placebo ingestion. RESULTS: Findings showed that all subjects who underwent odor stimulation presented activations of similar intensities in the olfactory centers of the brain. This contrasted with inhibitory regions of the brain such as the cingulate cortex and frontal lobe regions, which demonstrated changed activity patterns and intensities. While some differences between the placebo and medicated states were found in motor areas, precuneus, cuneus, calcarine, supramarginal, cerebellum and posterior cingulate cortex, the main changes were found in frontal, temporal and parietal cortices. When comparing olfactory cues separately, pleasant food smells like chocolate seemed not to present large differences between the medicated and placebo scenarios, when compared to non-food-related smells. CONCLUSION: It was demonstrated that LDX, first, altered the inhibitory pathways of the brain, secondly it increased activity in several brain regions which were not activated by smell in drug-naïve patients, and thirdly, it facilitated a complementary behavioral regulation mechanism, run by the cerebellum, which regulated decision-making and impulsivity in motor and frontal structures.

Levodopa Facilitates Prefrontal Cortex Activation During Dual Task Walking in Parkinson Disease.

Background. Although dopaminergic medication improves dual task walking in people with Parkinson disease (PD), the underlying neural mechanisms are not yet fully understood. As prefrontal cognitive resources are involved in dual task walking, evaluation of the prefrontal cortex (PFC) is required. Objective. To investigate the effect of dopaminergic medication on PFC activity and gait parameters during dual task walking in people with PD. Methods. A total of 20 individuals with PD (69.8 ± 5.9 years) and 30 healthy older people (68.0 ± 5.6 years) performed 2 walking conditions: single and dual task (walking while performing a digit vigilance task). A mobile functional near infrared spectroscopy system and an electronic sensor carpet were used to analyze PFC activation and gait parameters, respectively. Relative concentrations of oxygenated hemoglobin (HbO2) from the left and right PFC were measured. Results. People with PD in the off state did not present changes in HbO2 level in the left PFC across walking conditions. In contrast, in the on state, they presented increased HbO2 levels during dual task compared with single task. Regardless of medication state, people with PD presented increased HbO2 levels in the right PFC during dual task walking compared with single task. The control group demonstrated increased PFC activity in both hemispheres during dual task compared with single task. People with PD showed increases in both step length and velocity in the on state compared with the off state. Conclusions. PD limits the activation of the left PFC during dual task walking, and dopaminergic medication facilitates its recruitment.

Effects of semantic categorization strategy training on episodic memory in children and adolescents.

Episodic memory is the ability to learn, store and recall new information. The prefrontal cortex (PFC) is a crucial area engaged in this ability. Cognitive training has been demonstrated to improve episodic memory in adults and older subjects. However, there are no studies examining the effects of cognitive training on episodic memory encoding in typically developing children and adolescents. This study investigated the behavioral effects and neural correlates of semantic categorization strategy training in children and adolescents during verbal episodic memory encoding using functional magnetic resonance imaging (fMRI). Participants with age range: 7-18 years were scanned before and after semantic categorization training during encoding of word lists. Results showed improved memory performance in adolescents, but not in children. Deactivation of the anterior medial PFC/anterior cingulate and higher activation of the right anterior and lateral orbital gyri, right frontal pole and right middle frontal gyrus activation were found after training in adolescents when compared to children. These findings suggest different maturational paths of brain regions, especially in the PFC, and deactivation of default mode network areas, which are involved in successful memory and executive processes in the developing brain.

Brain Marker Links Stress and Nicotine Abstinence.

BACKGROUND: Subjective stress is a well-documented predictor of early smoking relapse, yet our understanding of stress and tobacco use is limited by reliance on self-reported measures of stress. We utilized a validated functional neuroimaging paradigm to examine whether stress exposure during early abstinence alters objective measures of brain function. METHODS: Seventy-five participants underwent blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) during the Montreal Imaging Stress Task (MIST) on two occasions: once during smoking satiety and once following biochemically confirmed 24-hour abstinence (order counterbalanced). The primary outcome measure was brain response during stress (vs. control) blocks of the MIST, assessed using whole-brain analysis corrected for multiple comparisons using clusters determined by Z ≥ 3.1. RESULTS: Abstinence (vs. satiety) was associated with significantly increased activation in the left inferior frontal gyrus, a brain region associated with inhibitory control. Abstinence-induced change in brain response to stress was positively associated with change in self-reported stress. CONCLUSIONS: This study provides objective evidence that the brain response to stress is altered during the first 24 hours of a quit attempt compared to smoking satiety. IMPLICATIONS: These results point to the potential value of inoculating smokers with stress management training prior to a quit attempt.

Chronic low back pain and sick-leave: a functional magnetic resonance study

Abstract Background Chronic low back pain (CLBP) represents a problem in the occupational environment, often associated with disability, sick-leave demands, loss of productivity, anxiety, depression and high socioeconomic cost. The emergence of functional neuroimaging allowed new insights into brain structure and physiology in normality and chronic pain. While occupational related aspects are recognized as important risk factors for chronicity there have not been thus far evaluated by fMRI experiments. The overall objective of this study is to compare the neuronal correlates between groups of individuals CLBP with or without sick-leave demands. Methods A total of 74 individuals were divided into three groups: chronic low back pain with sick-leave demands [CLBP_L]; chronic low back pain without sick-leave demands [CLBP_NL]; individuals without pain or sick-leave demands [Control]. Functional magnetic resonance imaging was used to assess brain function during moderate acute pain stimulation task (thumb controlled pressure). Results After acute painful stimulation, a higher brain response was found in the anterior cingulate and superior and medium frontal gyrus was observed in CLBP_NL vs. CLBP_L ( p < 0,001) and increased brain response in the frontal pole and paracingulate region in control vs. CLBP_L ( p < 0.001) during acute pain stimulation. Conclusion The modulation of acute pain participates in the mechanism propagating chronic pain perception. The lower activation in the superior frontal gyrus observed in the CLBP_L group compared to CLBP_NL, reinforces the idea of an already existing activation in this area.(AU)

Test-retest reproducibility of a multi-atlas automated segmentation tool on multimodality brain MRI.

INTRODUCTION: The increasing use of large sample sizes for population and personalized medicine requires high-throughput tools for imaging processing that can handle large amounts of data with diverse image modalities, perform a biologically meaningful information reduction, and result in comprehensive quantification. Exploring the reproducibility of these tools reveals the specific strengths and weaknesses that heavily influence the interpretation of results, contributing to transparence in science. METHODS: We tested-retested the reproducibility of MRICloud, a free automated method for whole-brain, multimodal MRI segmentation and quantification, on two public, independent datasets of healthy adults. RESULTS: The reproducibility was extremely high for T1-volumetric analysis, high for diffusion tensor images (DTI) (however, regionally variable), and low for resting-state fMRI. CONCLUSION: In general, the reproducibility of the different modalities was slightly superior to that of widely used software. This analysis serves as a normative reference for planning samples and for the interpretation of structure-based MRI studies.

Relationships Between Executive Control Circuit Activity, Amyloid Burden, and Education in Cognitively Healthy Older Adults.

INTRODUCTION: In cognitively healthy older adults, amyloid-beta (Aß) burden is associated with greater activity on task-based functional magnetic resonance imaging. Higher levels of functional activation are associated with other factors along with amyloid and the authors investigated these relationships as well as how they relate to Aß in cognitively healthy older adults. METHODS: The authors recruited cognitive healthy older adults (N = 50) from the Pittsburgh community that underwent extensive cognitive batteries, activation during a working memory (digit symbol substitution task, DSST), positron emission tomography scan for Pittsburgh Compound B (PiB, measuring amyloid), and other demographic measures. The authors tested the association between DSST activation and global PiB, neurocognitive batteries, and education. RESULTS: The authors found that the DSST robustly activated expected structures involved in working memory. The authors found that greater global Aß deposition was associated with greater DSST activation in the right calcarine, precuneus, middle temporal as well as the left insula and inferior frontal gyrus. The authors also found that greater education was associated with lower DSST activation - however this was not significant after adjusting for Aß. DISCUSSION: Greater amyloid was associated with greater activation, which may represent compensatory activation. Greater education was associated with lower activation, which may represent more efficient activation (i.e., less activation for the same task). After adjusting for amyloid, education was not significantly associated with activation suggesting that during the preclinical stage amyloid is the primary determinant of activation. Further, activation was not associated with cognitive function. Compensatory activation in the preclinical stage may help maintain cognitive function.

Genetic risk for Alzheimer's disease and functional brain connectivity in children and adolescents.

Research suggested accumulation of tau proteins might lead to the degeneration of functional networks. Studies investigating the impact of genetic risk for Alzheimer's disease (AD) on early brain connections might shed light on mechanisms leading to AD development later in life. Here, we aim to investigate whether the polygenic risk score for Alzheimer's disease (AD-PRS) influences the connectivity among regions susceptible to tau pathology during childhood and adolescence. Participants were youth, aged 6-14 years, and recruited in Porto Alegre (discovery sample, n = 332) and São Paulo (replication sample, n = 304), Brazil. Subjects underwent genotyping and 6-min resting state funcional magnetic resonance imaging. Connections between the local maxima of tau pathology networks were used as dependent variables. The AD-PRS was associated with the connectivity between the right precuneus and the right superior temporal gyrus (discovery sample: ß = 0.180, padjusted = 0.036; replication sample: ß = 0.202, p = 0.031). This connectivity was also associated with inhibitory control (ß = 0.157, padjusted = 0.035) and moderated the association between the AD-PRS and both immediate and delayed recall. These findings suggest the AD-PRS may affect brain connectivity in youth, which might impact memory performance and inhibitory control in early life.