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BACKGROUND: Preterm birth is one of the world's critical health problems, with an incidence of 5% to 18% of living newborns according to various countries. White matter injuries due to preoligodendrocytes deficits cause hypomyelination in children born preterm. Preterm infants also have multiple neurodevelopmental sequelae due to prenatal and perinatal risk factors for brain damage. The purpose of this work was to explore the effects of the brain risk factors and MRI volumes and abnormalities on the posterior motor and cognitive development at 3 years of age. METHODS: A total of 166 preterm infants were examined before 4 months and clinical and MRI evaluations were performed. MRI showed abnormal findings in 89% of the infants. Parents of all infants were invited to receive the Katona neurohabilitation treatment. The parents of 128 infants accepted and received Katona's neurohabilitation treatment. The remaining 38 infants did not receive treatment for a variety of reasons. At the three-year follow-up, Bayley's II Mental Developmental Index (MDI) and the Psychomotor Developmental Index (PDI) were compared between treated and untreated subjects. RESULTS: The treated children had higher values of both indices than the untreated. Linear regression showed that the antecedents of placenta disorders and sepsis as well as volumes of the corpus callosum and of the left lateral ventricle significantly predicted both MDI and PDI, while Apgar < 7 and volume of the right lateral ventricle predicted the PDI. CONCLUSIONS: (1) The results indicate that preterm infants who received Katona's neurohabilitation procedure exhibited significantly better outcomes at 3 years of age compared to those who did not receive the treatment. (2) The presence of sepsis and the volumes of the corpus callosum and lateral ventricles at 3-4 months were significant predictors of the outcome at 3 years of age.

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BACKGROUND: In healthy older adults, excess theta activity is an electroencephalographic (EEG) predictor of cognitive impairment. In a previous study, neurofeedback (NFB) treatment reinforcing reductions theta activity resulted in EEG reorganization and cognitive improvement. OBJECTIVE: To explore the clinical applicability of this NFB treatment, the present study performed a 1-year follow-up to determine its lasting effects. METHODS: Twenty seniors with excessive theta activity in their EEG were randomly assigned to the experimental or control group. The experimental group received an auditory reward when the theta absolute power (AP) was reduced. The control group received the reward randomly. RESULTS: Both groups showed a significant decrease in theta activity at the training electrode. However, the EEG results showed that only the experimental group underwent global changes after treatment. These changes consisted of delta and theta decreases and beta increases. Although no changes were found in any group during the period between the posttreatment evaluation and follow-up, more pronounced theta decreases and beta increases were observed in the experimental group when the follow-up and pretreatment measures were compared. Executive functions showed a tendency to improve two months after treatment which became significant one year later. CONCLUSION: These results suggest that the EEG and behavioral benefits of this NFB treatment persist for at least one year, which adds up to the available evidence contributing to identifying factors that increase its efficacy level. The relevance of this study lies in its prophylactic features of addressing a clinically healthy population with EEG risk of cognitive decline.

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This study aims to examine how two levels of cognitive reserve, as evidenced by reading syntactic skill, modify performance and neural activity in a two-load-level (high vs. low) working memory (WM) task. Two groups of participants with different reading skills, high and low, were obtained from clustering analysis. We collected the P300 event-related potential component during the performance of the WM Sternberg task. The high reading performance (HRP) group showed a higher percentage of correct answers than the low reading performance (LRP) group in the negative probes of the WM task, which were probe stimuli not included in the memory set presented immediately before. Both groups showed P300 amplitude modulations, that is, larger WM-related P300 amplitudes for low than for high WM loads. Following the behavioral results, the HRP group displayed smaller WM-related amplitude modulations than the LRP group in the negative probes. The findings together suggest that higher levels of reading skill are associated with improved neural efficiency, which reflects in a better working memory performance.

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BACKGROUND: Neurocognitive disorders (NCDs) are characterized by cognitive decline. Most genetic studies of NCDs have been focused on single-nucleotide polymorphism; other genetic variations, such as copy number variants (CNV), have been less explored. The aim of the present study was to explore CNVs associated with NCDs in a small sample of Mexican individuals and search for the frequency in a larger replication sample of individuals at high-risk for or diagnosed with NCDs. METHOD: The exploratory analysis analyzed whole-genome CNVs associated with NCDs in 1335 individuals, of whom 35 were diagnosed with NCDs and 1300 were population-based controls. Whole-genome CNVs were derived from PsychArray and the PennCNV algorithm. The frequency of associated CNVs in a sample of 277 individuals diagnosed with NCDs and 70 high-risk individuals was then determined using RT-PCR. RESULTS: The exploratory analysis identified one deletion associated with NCDs (p = 0.007) affecting the gene MGAT4C (Mannosyl (Alpha-1,3-)-Glycoprotein Beta-1,4-N-Acetylglucosaminyltransferase, Isozyme C). In the replication sample, a frequency of 3.97% was found in individuals diagnosed with NCDs and 1.43% in high-risk individuals. CONCLUSIONS: An association between a rare CNV on MGAT4C and cognitive impairment was found in this sample of the Mexican population. Nevertheless, studies with larger sample sizes are needed in order to further explore the association.

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INTRODUCTION: Dyscalculia is a specific learning disorder affecting the ability to learn certain math processes, such as arithmetic data recovery. The group of children with dyscalculia is very heterogeneous, in part due to variability in their working memory (WM) deficits. To assess the brain response to arithmetic data recovery, we applied an arithmetic verification task during an event-related potential (ERP) recording. Two effects have been reported: the N400 effect (higher negative amplitude for incongruent than for congruent condition), associated with arithmetic incongruency and caused by the arithmetic priming effect, and the LPC effect (higher positive amplitude for the incongruent compared to the congruent condition), associated with a reevaluation process and modulated by the plausibility of the presented condition. This study aimed to (a) compare arithmetic processing between children with dyscalculia and children with good academic performance (GAP) using ERPs during an addition verification task and (b) explore, among children with dyscalculia, the relationship between WM and ERP effects. MATERIALS AND METHODS: EEGs of 22 children with dyscalculia (DYS group) and 22 children with GAP (GAP group) were recorded during the performance of an addition verification task. ERPs synchronized with the probe stimulus were computed separately for the congruent and incongruent probes, and included only epochs with correct answers. Mixed 2-way ANOVAs for response times and correct answers were conducted. Comparisons between groups and correlation analyses using ERP amplitude data were carried out through multivariate nonparametric permutation tests. RESULTS: The GAP group obtained more correct answers than the DYS group. An arithmetic N400 effect was observed in the GAP group but not in the DYS group. Both groups displayed an LPC effect. The larger the LPC amplitude was, the higher the WM index. Two subgroups were found within the DYS group: one with an average WM index and the other with a lower than average WM index. These subgroups displayed different ERPs patterns. DISCUSSION: The results indicated that the group of children with dyscalculia was very heterogeneous and therefore failed to show a robust LPC effect. Some of these children had WM deficits. When WM deficits were considered together with dyscalculia, an atypical ERP pattern that reflected their processing difficulties emerged. Their lack of the arithmetic N400 effect suggested that the processing in this step was not useful enough to produce an answer; thus, it was necessary to reevaluate the arithmetic-calculation process (LPC) in order to deliver a correct answer. CONCLUSION: Given that dyscalculia is a very heterogeneous deficit, studies examining dyscalculia should consider exploring deficits in WM because the whole group of children with dyscalculia seems to contain at least two subpopulations that differ in their calculation process.

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Semantic verbal fluency (VF), assessed by animal category, is a task widely used for early detection of dementia. A feature not regularly assessed is the occurrence of errors such as perseverations and intrusions. So far, no investigation has analyzed the how and when of error occurrence during semantic VF in aging populations, together with their possible neural correlates. The present study aims to address the issue using a combined methodology based on latent Dirichlet allocation (LDA) analysis for word classification together with a time-course analysis identifying exact time of errors' occurrence. LDA is a modeling technique that discloses hidden semantic structures based on a given corpus of documents. We evaluated a sample of 66 participants divided into a healthy young group (n = 24), healthy older adult group (n = 23), and group of patients with mild Alzheimer's disease (AD) (n = 19). We performed DTI analyses to evaluate the white matter integrity of three frontal tracts purportedly underlying error commission: anterior thalamic radiation, frontal aslant tract, and uncinate fasciculus. Contrasts of DTI metrics were performed on the older groups who were further classified into high-error rate and low-error rate subgroups. Results demonstrated a unique deployment of error commission in the patient group characterized by high incidence of intrusions in the first 15 s and higher rate of perseverations toward the end of the trial. Healthy groups predominantly showed very low incidence of perseverations. The DTI analyses revealed that the patients with AD committing high-error rate presented significantly more degenerated frontal tracts in the left hemisphere. Thus, our findings demonstrated that the appearance of intrusions, together with left hemisphere degeneration of frontal tracts, is a pathognomic trait of mild AD. Furthermore, our data suggest that the error commission of patients with AD arises from executive and working memory impairments related partly to deteriorated left frontal tracts.

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BACKGROUND: Identification of the cognitive mechanisms behind gait changes in aging is a prime endeavor in gerontology and geriatrics. For this reason, we have implemented a new dual-task paradigm where an auditory attentional task is performed during over-ground walking. Dichotic listening assesses spontaneous attention and voluntary attention directed to right and left-ear. The uniqueness of dichotic listening relies on its requirements that vary in difficulty and recruitment of resources from whole brain to one brain hemisphere. When used in dual-tasking, asymmetric effects on certain gait parameters have been reported. OBJECTIVES: The present study aims to acquire a more global understanding on how dichotic listening affects gait domains. Specifically, we aimed to understand how spontaneous vs lateralized auditory attention altered the Principal Component Analysis (PCA) structure of gait in healthy older adults. METHODS: Seventy-eight healthy older adults (mean age: 71.1 years; 44 women and 34 men) underwent the Bergen dichotic listening test while walking. As this study only focuses on the effects of the cognitive task on gait, only dual-task costs for gait were calculated and entered into the PCA analyses. We explored the PCA structure for the effects on bilateral gait parameters (i.e., both limbs together) as well as on lateralized gait parameters (i.e, separate parameters by limb). We first established gait domains during single-task walking. Then, dual-task cost scores for gait were entered in a series of PCAs. RESULTS: Results from the PCAs for bilateral gait parameters showed limited alterations on gait structure. In contrast, PCAs for lateralized data demonstrated modifications of the gait structure during dichotic listening. The PCAs corresponding for all dichotic listening conditions showed different factor solutions ranging between 4 and 6 factors that explained between 73.8% to 80% of the total variance. As a whole, all conditions had an impact on "pace", "pace variability" and "base of support variability" domains. In the spontaneous attention condition, a six-factor solution explaining 78.3% of the variance showed asymmetrical disruptions on the PCA structure. When attention was focused to right-ear, a five-factor solution explaining 89% of the variance and similar to baseline was found. When attention was directed to left-ear, a four-factor solution explaining 73.8% of the variance was found with symmetrical impact on all factors. CONCLUSIONS: These findings demonstrate for the first time that specific facets of attentional control affects gait domains both symmetrically and asymmetrically in healthy older adults.

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BACKGROUND: White matter hyperintensities (WMH) are a common cerebral finding in older people. WMH are usually asymptomatic, but excessive WMH are associated with cognitive decline and dementia. WMH are also among the neurological findings most consistently associated with declining motor performance in healthy ageing. AIMS: To determine if WMH load is associated with simple and complex motor movements in dominant and non-dominant hands in cognitively intact older subjects. METHODS: Hand motor performance was assessed with the Purdue Pegboard and Finger-tapping tests on 44 healthy right-handed participants, mean age 70.9 years (range 59-84 years). Participants also underwent magnetic resonance (MR) imaging, which were used to quantify WMH volume. The effect of WMH on the motor parameters was assessed via mediation analyses. RESULTS: WMH load increased significantly with age, while the motor scores decreased significantly with age. WMH load mediated only the relationship between age and left-hand pegboard scores. DISCUSSION: WMH mediated only the more complex Purdue Pegboard task for the non-dominant hand. This is likely because complex movements in the non-dominant hand recruit a larger cerebral network, which is more vulnerable to WMH. CONCLUSIONS: Complex hand movements in the non-dominant hand are mediated by WMH. Subtle loss of motor movements of non-dominant hand might predict future excessive white matter atrophy.

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Semantic verbal fluency is among the most employed tasks in cognitive aging research and substantial work is devoted to understanding the underlying mechanisms behind age-related differences at the neural and behavioral levels. The present investigation aimed to evaluate the role of moderating variables, such as age, sex, MMSE, and proxies of cognitive reserve (CR) on the hemodynamic response evoked by semantic verbal fluency in healthy young and healthy older adults. So far, no study has been conducted to this end. To elucidate the exclusive effect of the mentioned variables on brain activation during semantic fluency, finger tapping was included as a control task. Results showed that disregarding adjustments for age, older adults displayed important parietal activations during semantic fluency as well as during finger-tapping. Specifically, the anterior intra-parietal sulcus (IPS) and left inferior parietal lobule (IPL) were areas activated in both tasks in the older group. Younger adults, only displayed parietal activations related to age and sex when these demographics were employed as predictors. Concerning proxies of CR in semantic fluency, the only vocabulary was an important moderator in both age groups. Higher vocabulary scores were associated with lesser activation in occipital areas. Education did not show significant correlations with brain activity during semantic fluency in any of the groups. However, both CR proxies were significantly correlated to brain activations of older adults during finger tapping. Specifically, vocabulary was associated with frontal regions, while education correlated with parietal lobe and cingulate gyrus. Finally, the effects of MMSE were mostly observed on brain activation of older adults in both tasks. These findings demonstrate that the effects of moderating variables on shaping brain activation are intricate and not exclusive of complex verbal tasks. Thus, before adjusting for "nuisance variables," their importance needs to be established. This is especially true for samples including older adults for whom a motor task may be a demanding operation due to normal age-related processes of dedifferentiation.

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To date the neural mechanisms behind gait perturbations caused by dual-task paradigms are still unknown. Therefore, the present study examined white matter correlates of gait perturbations caused by a dichotic listening task where spontaneous (free focus of attention) and lateralized attentional control (voluntary attention directed to right or left-ear) were tested. Fifty-nine right-handed, healthy older adults (59-88 years) were evaluated during single-task walking and three dual-task conditions. Dual-task costs were calculated for mean (DTCM) and coefficients of variation (DTCCoV) in gait speed, step length, stride length and step width. Volume, fractional anisotropy and mean diffusivity were estimated using global probabilistic tractography for the 18 major brain tracts and correlated with the DTCs. Data demonstrated that DTCs on gait speed and step length significantly correlated with white matter integrity and volume in various tracts. Perturbations on gait speed caused by spontaneous attention were related to frontal circuitry integrity including corpus callosum, while perturbations on gait speed and step length produced by voluntary lateralized attention were associated to tracts subserving visuomotor integration and frontal function.

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INTRODUCTION: In Mexico, the prevalence of neurocognitive disorders (NCDs) has increased in parallel with the increase in life expectancy. The E4 allele of the gene that encodes apolipoprotein E (APOE) is the main genetic risk factor for cognitive impairment. OBJECTIVE: To replicate the association of APOE-E4 allele with neurocognitive impairment in a Mexican population, as well as to implement a genetic risk-detection program with the APOE-E4 allele. METHOD: A program was structured for the detection of APOE-E4 allele risk in different recruiting centers from the central zone of the Mexican Republic, with three stages: recruitment and selection of candidates for the detection of the risk-allele, genetic risk analysis and delivery of results. RESULTS: In the genetic-association study to replicate the association with neurocognitive disorders by means of multivariate logistic models, the APOE-E4 allele increased the risk for cognitive impairment in the Mexican populations by approximately 6 % (OR: 5.83, p = 0.0025). In addition, 367 genetic risk results were delivered. CONCLUSIONS: The present program is the first one to be implemented in Mexico with the purpose to inform on a genetic risk factor for neurocognitive disorders in several centers of the country.

INTRODUCCIÓN: En México, la prevalencia de los trastornos neurocognitivos (TNC) han aumentado a la par del incremento en la esperanza de vida. El alelo E4 del gen que codifica la apolipoproteína E (APOE) es el principal factor de riesgo genético para deterioro neurocognitivo. OBJETIVO: Reproducir la asociación en población mexicana entre APOE-E4 y el deterioro neurocognitivo, así como implementar un programa de detección de riesgo genético con el alelo APOE-E4. MÉTODO: Se estructuró un programa de detección de riesgo basado en APO-EA en diferentes centros de reclutamiento en la zona centro de la República Mexicana, con tres etapas: reclutamiento y selección de los candidatos para la detección del alelo de riesgo, análisis del riesgo genético y entrega del resultado. RESULTADOS: El análisis de asociación genética para replicar la asociación con trastornos neurocognitivos mediante modelos logísticos multivariados mostró que el alelo E4 de APOE incrementó aproximadamente 6 % el riesgo en población mexicana (RM = 5.83, p = 0.0025). Se entregaron 367 resultados de riesgo genético. CONCLUSIONES: El presente programa es el primero en México implementado para dar a conocer un factor de riesgo genético para trastornos neurocognitivos en varios centros del país.

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Cognitive changes in aging include working memory (WM) decline, which may hamper language comprehension. An increase in WM demands in older adults would probably provoke a poorer sentence processing performance in this age group. A way to increase the WM load is to separate two lexical units in an agreement relation (i.e., adjective and noun), in a given sentence. To test this hypothesis, event-related potentials (ERPs) were collected from Spanish speakers (30 older adults, mean age = 66.06 years old; and 30 young adults, mean age = 25.7 years old) who read sentences to detect grammatical errors. The sentences varied with regard to (1) the gender agreement of the noun and adjective, where the gender of the adjective either agreed or disagreed with the noun, and (2) the WM load (i.e., the number of words between the noun and adjective in the sentence). No significant behavioral differences between groups were observed in the accuracy of the response, but older adults showed longer reaction times regardless of WM load condition. Compared with young participants, older adults showed a different pattern of ERP components characterized by smaller amplitudes of LAN, P600a, and P600b effects when the WM load was increased. A smaller LAN effect probably reflects greater difficulties in processing the morpho-syntactic features of the sentence, while smaller P600a and P600b effects could be related to difficulties in recovering and mapping all sentence constituents. We concluded that the ERP pattern in older adults showed subtle problems in syntactic processing when the WM load was increased, which was not sufficient to affect response accuracy but was only observed to result in a longer reaction time.

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High levels of physical activity seem to positively influence health and cognition across the lifespan. Several studies have found that aerobic exercise enhances cognition and likely prevents cognitive decline in the elderly. Nevertheless, the association of incidental physical activity (IPA) with health and cognition during aging has not been studied. Thus, the aim of this study was to evaluate the association of IPA level with cognitive functions and resting electroencephalogram (EEG) in healthy old participants. Participants (n = 97) with normal scores on psychometric and neuropsychological tests and normal values in blood analyses were included. A cluster analysis based on the scores of the Yale Physical Activity Scale (YPAS) allowed the formation of two groups: active, with high levels of IPA, and passive, with low levels of IPA. Eyes-closed resting EEG was recorded from the participants; the fast Fourier transform was used offline to calculate absolute power (AP), relative power (RP), and mean frequency (MF) measures. There were no differences in socioeconomic status, cognitive reserve, general cognitive status, or lipid and TSH profiles between the groups. The results of cognitive tests revealed significant differences in the performance variables of the WAIS scores (p = .015), with advantages for the active group. The resting EEG exhibited significantly slower activity involving the frontal, central, and temporal regions in the passive group (p < .05). Specifically, higher delta RP (F7, T3), lower delta MF (F4, C4, T4, T6, Fz, Cz), higher theta AP (C4), higher theta RP (F4, C4, T3, Fz), lower alpha AP (F3, F7, T3), lower alpha RP (F7), and lower total MF (F3, F7, T3, T5, Fz) were found. Altogether, these results suggest that IPA induces a neuroprotective effect, which is reflected both in behavioral and electrophysiological variables during aging.

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Excess theta electroencephalographic (EEG) activity has been described as an accurate predictor for cognitive decline at least 7 years before symptom presentation. To test whether this predictor for cognitive decline correlates with structural changes in the brains of healthy elderly individuals, we compared the magnetic resonance structural images of healthy individuals with excess of theta activity [group with a risk for cognitive decline, risk group (RG); n=14] with healthy controls with normal EEG activity (control group; n=14). Neuropsychological and epidemiological analyses showed significant differences in only two features: more years of education and better performance in the visuospatial process task in the control group. Voxel-based morphometry results were not conclusive, but showed tendencies toward larger volumes in the prefrontal and parietal lobes, and smaller volumes in the right temporal lobe, right occipital lobe, and left cerebellum for the RG; these tendencies are in agreement with those proposed by the posterior-anterior shift in an aging model. Cortical-thickness analyses yielded a significant correlation between cortical thickness and years of education in the prefrontal and inferior-temporal regions, and larger cortical thickness in the RG, independent of age and years of education, in the right superior temporal region. These results suggest changes in the cortical thickness of structures related to memory and visuospatial functions in healthy, cognitively normal individuals before the appearance of cognitive decline. Thus, the performance of healthy elderly individuals with EEG risk may only be slightly different from normal because of compensation mechanisms allowing them to fulfill daily-life tasks, masking structural changes during preclinical neurocognitive disorders.

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OBJECTIVES: Malnourishment (M) produces permanent alterations during the development of the CNS and might modify the aging process. In pyramidal neurons (PN) of the hippocampus, which are associated with learning and memory performance, few studies have focused on changes at the subcellular level under chronic malnutrition (ChM) in young (Y, 2 months old) and aged (A, 22 months old) rats. The present work evaluated the extent to which ChM disrupts organelles in PN of the dorsal hippocampus CA1 as compared to controls (C). METHODS: Ultrastructural analysis was performed at 8000× and 20 000× magnification: Nucleus eccentricity and somatic, cytoplasmic, and nuclear areas were measured; and in the PN perikaryon, density indices (number of organelles/cytoplasmic area) of Golgi membrane systems (GMS, normal, and swollen), mitochondria (normal and abnormal), and vacuolated organelles (lysosomes, lipofuscin granules, and multivesicular bodies (MVB)) were determined. RESULTS: The density of abnormal mitochondria, swollen GMS, and MVB increased significantly in the AChM group compared to the other groups. The amount of lipofuscin was significantly greater in the AChM than in the YChM groups - a sign of oxidative stress due to malnutrition and aging; however, in Y animals, ChM showed no effect on organelle density or the cytoplasmic area. An increased density of lysosomes as well as nucleus eccentricity was observed in the AC group, which also showed an increase in the cytoplasmic area. DISCUSSION: Malnutrition produces subcellular alterations in vulnerable hippocampal pyramidal cells, and these alterations may provide an explanation for the previously reported deficient performance of malnourished animals in a spatial memory task in which aging and malnutrition were shown to impede the maintenance of long-term memory.

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