Brain structural change associated with Cognitive Behavioral Therapy in maltreated children.

BACKGROUND: Severely maltreatment child is a harmful social factor that can disrupt normal neurodevelopment. Two commonly reported effects of maltreatment are post-traumatic stress disorder (PTSD) symptoms and brain structural and functional alteration. While Trauma-Focused Cognitive-Behavioral Therapy (TF-CBT) is effectively used to reduce PTSD symptoms in maltreated children, yet, its impact on brain structural alterations has not been fully explored. This study investigated whether TF-CBT can attenuate alterations in brain structures associated with PTSD in middle childhood. METHODS: The study evaluated the longitudinal effects of Trauma-Focused Cognitive-Behavioral Therapy (TF-CBT) on post-traumatic stress disorder (PTSD) symptoms and gray matter volume (GMV) in two groups of children under 12 years old: maltreated children (MC) and healthy non- maltreatmentd children (HC). Structural magnetic resonance images T1 were obtained before and after TF-CBT in the MC group, while the HC group was scanned twice within the same time interval. Voxel-based morphometry (VBM) was used to analyze GMV changes over time. RESULTS: After TF-CBT, maltreated children showed significantly reduced PTSD symptoms. Furthermore, a significant group-by-time interaction effect was observed in certain areas of the Left Temporal, Left Occipital, and bilateral Frontal Cortex, the Basal Ganglia and Cerebellum. These interaction effects were driven by a GMV decrease in the MC group compared to the HC group. GMV changes can be predicted with clinical improvement in the left Middle Temporal gyrus, left Precuneus, and Cerebellum. CONCLUSIONS: Our results suggest that TF-CBT intervention in very young maltreated children may have an effect on gray matter. This evidence demonstrates the importance of timely intervention when neuroplasticity mechanisms may be activated.

Can psychopathy be prevented? Clinical, neuroimaging, and genetic data: an exploratory study.

The aim of the study was to explore the relationship among brain functional activations elicited by an emotional paradigm, clinical scores (PTSD, anxiety, and depression), psychopathic traits, and genetic characteristics (5-HTTLPR) in a group of severely maltreated children compared to a healthy control group before and after the implementation of a Trauma Focused-Cognitive Behavioral Therapy. The final sample consisted of an experimental group of 14 maltreated children (mean age = 8.77 years old, S.D. = 1.83) recruited from a non-governmental shelter in Mexico City for children who had experienced child abuse and a control group of 10 children from the general population (mean age = 9.57 years old, S.D. = 1.91). Both groups were matched according to age and gender and were assessed before and after the implementation of the aforementioned therapy by means of clinical scales and an emotional paradigm that elicited brain activations which were recorded through functional magnetic resonance imaging. Genotyping of the 5-HTTLPR polymorphism was made at first assessment. A region of interest analysis showed amygdala hyperactivation during exposure to fear and anger stimuli in the maltreated children before treatment. Following therapy, a decrease in brain activity as well as a decrease in clinical symptoms were also observed. 5-HTTLPR polymorphism did not show any effect on the severity of clinical symptoms in maltreated children. Trauma-Focused Behavioral Therapy may help reorganize the brain's processing of emotional stimuli. These observations reveal the importance of an early intervention when the mechanisms of neuroplasticity may be still recruited.

Anatomical connections underlying personally-familiar face processing.

Familiar face processing involves face specific regions (the core face system) as well as other non-specific areas related to processing of person-related information (the extended face system). The connections between core and extended face system areas must be critical for face recognition. Some studies have explored the connectivity pattern of unfamiliar face responding area, but none have explored those areas related to face familiarity processing in the extended system. To study these connections, diffusion weighted imaging with probabilistic tractography was used to estimate the white-matter pathways between core and extended system regions, which were defined from functional magnetic resonance imaging responses to personally-familiar faces. Strong white matter connections were found between occipitotemporal face areas (OFA/FFA) with superior temporal sulcus and insula suggesting the possible existence of direct anatomical connections from face-specific areas to frontal nodes that could underlay the processing of emotional information associated to familiar faces.

ERP Source Analysis Guided by fMRI During Familiar Face Processing.

Event related potentials (ERPs) provide precise temporal information about cognitive processing, but with poor spatial resolution, while functional magnetic resonance imaging (fMRI) reliably identifies brain areas involved, but with poor temporal resolution. Here we use fMRI to guide source localization of the ERPs at different times for studying the temporal dynamics of the neural system for recognizing familiar faces. fMRI activation areas were defined in a previous experiment applying the same paradigm used for ERPs. The Bayesian model averaging (BMA) method was used to estimate the generators of the ERPs to unfamiliar, visually familiar, and personally-familiar faces constraining the model by fMRI activation results. For this, higher prior probabilities in the solution space were assigned to the fMRI-defined regions, which included face-selective areas and other areas related to "person knowledge" retrieval. Source analysis was carried out in three-time windows: early (150-210 ms), middle (300-380 ms) and late (460-580 ms). The early and middle responses were generated in fMRI-defined areas for all face categories, while these areas do not contribute to the late response. Different areas contributed to the generation of the early and middle ERPs elicited by unfamiliar faces: fusiform (Fus), inferior occipital, superior temporal sulcus and the posterior cingulate (PC) cortices. For familiar faces, the contributing areas were Fus, PC and anterior temporal areas for visually familiar faces, with the addition of the medial orbitofrontal areas and other frontal structures for personally-significant faces. For both unfamiliar and familiar faces, more extended and reliable involvement of contributing areas were obtained for the middle compare with early time window. Our fMRI guide ERP source analysis suggested the recruitment of person-knowledge processing areas as early as 150-210 ms after stimulus onset during recognition of personally-familiar faces. We concluded that fMRI-constrained BMA source analysis provide information regarding the temporal-dynamics in the neural system for cognitive processsing.

Source Reconstruction of Brain Potentials Using Bayesian Model Averaging to Analyze Face Intra-Domain vs. Face-Occupation Cross-Domain Processing.

We investigated the neural correlates of the access to and retrieval of face structure information in contrast to those concerning the access to and retrieval of person-related verbal information, triggered by faces. We experimentally induced stimulus familiarity via a systematic learning procedure including faces with and without associated verbal information. Then, we recorded event-related potentials (ERPs) in both intra-domain (face-feature) and cross-domain (face-occupation) matching tasks while N400-like responses were elicited by incorrect eyes-eyebrows completions and occupations, respectively. A novel Bayesian source reconstruction approach plus conjunction analysis of group effects revealed that in both cases the generated N170s were of similar amplitude but had different neural origin. Thus, whereas the N170 of faces was associated predominantly to right fusiform and occipital regions (the so-called "Fusiform Face Area", "FFA" and "Occipital Face Area", "OFA", respectively), the N170 of occupations was associated to a bilateral very posterior activity, suggestive of basic perceptual processes. Importantly, the right-sided perceptual P200 and the face-related N250 were evoked exclusively in the intra-domain task, with sources in OFA and extensively in the fusiform region, respectively. Regarding later latencies, the intra-domain N400 seemed to be generated in right posterior brain regions encompassing mainly OFA and, to some extent, the FFA, likely reflecting neural operations triggered by structural incongruities. In turn, the cross-domain N400 was related to more anterior left-sided fusiform and temporal inferior sources, paralleling those described previously for the classic verbal N400. These results support the existence of differentiated neural streams for face structure and person-related verbal processing triggered by faces, which can be activated differentially according to specific task demands.

Dynamic Causal Modeling of Preclinical Autosomal-Dominant Alzheimer's Disease.

Dynamic causal modeling (DCM) is a framework for making inferences about changes in brain connectivity using neuroimaging data. We fitted DCMs to high-density EEG data from subjects performing a semantic picture matching task. The subjects are carriers of the PSEN1 mutation, which leads to early onset Alzheimer's disease, but at the time of EEG acquisition in 1999, these subjects were cognitively unimpaired. We asked 1) what is the optimal model architecture for explaining the event-related potentials in this population, 2) which connections are different between this Presymptomatic Carrier (PreC) group and a Non-Carrier (NonC) group performing the same task, and 3) which network connections are predictive of subsequent Mini-Mental State Exam (MMSE) trajectories. We found 1) a model with hierarchical rather than lateral connections between hemispheres to be optimal, 2) that a pathway from right inferotemporal cortex (IT) to left medial temporal lobe (MTL) was preferentially activated by incongruent items for subjects in the PreC group but not the NonC group, and 3) that increased effective connectivity among left MTL, right IT, and right MTL was predictive of subsequent MMSE scores.

Inferior fronto-temporo-occipital connectivity: a missing link between maltreated girls and neglectful mothers.

The neurobiological alterations resulting from adverse childhood experiences that subsequently may lead to neglectful mothering are poorly understood. Maternal neglect of an infant's basic needs is the most prevalent type of child maltreatment. We tested white matter alterations in neglectful mothers, the majority of whom had also suffered maltreatment in their childhood, and compared them to a matched control group. The two groups were discriminated by a structural brain connectivity pattern comprising inferior fronto-temporo-occipital connectivity, which constitutes a major portion of the face-processing network and was indexed by fewer streamlines in neglectful mothers. Mediation and regression analyses showed that fewer streamlines in the right inferior longitudinal fasciculus tract (ILF-R) predicted a poorer quality of mother-child emotional availability observed during cooperative play and that effect depended on the respective interactions with left and right inferior fronto-occipital fasciculi (IFO-R/L), with no significant impact of psychopathological and cognitive conditions. Volume alteration in ILF-R but not in IFO-L modulated the impact of having been maltreated on emotional availability. The findings suggest the altered inferior fronto-temporal-occipital connectivity, affecting emotional visual processing, as a possible common neurological substrate linking a history of childhood maltreatment with maternal neglect.

Testing the connections within face processing circuitry in Capgras delusion with diffusion imaging tractography.

Although Capgras delusion (CD) patients are capable of recognizing familiar faces, they present a delusional belief that some relatives have been replaced by impostors. CD has been explained as a selective disruption of a pathway processing affective values of familiar faces. To test the integrity of connections within face processing circuitry, diffusion tensor imaging was performed in a CD patient and 10 age-matched controls. Voxel-based morphometry indicated gray matter damage in right frontal areas. Tractography was used to examine two important tracts of the face processing circuitry: the inferior fronto-occipital fasciculus (IFOF) and the inferior longitudinal (ILF). The superior longitudinal fasciculus (SLF) and commissural tracts were also assessed. CD patient did not differ from controls in the commissural fibers, or the SLF. Right and left ILF, and right IFOF were also equivalent to those of controls. However, the left IFOF was significantly reduced respect to controls, also showing a significant dissociation with the ILF, which represents a selective impairment in the fiber-tract connecting occipital and frontal areas. This suggests a possible involvement of the IFOF in affective processing of faces in typical observers and in covert recognition in some cases with prosopagnosia.

The Functional Integration in the Sensory-Motor System Predicts Aging in Healthy Older Adults.

Healthy aging is typically accompanied by a decrease in the motor capacity. Although the disrupted neural representations and performance of movement have been observed in older age in previous studies, the relationship between the functional integration of sensory-motor (SM) system and aging could be further investigated. In this study, we examine the impact of healthy aging on the resting-state functional connectivity (rsFC) of the SM system, and investigate as to how aging is affecting the rsFC in SM network. The SM network was identified and evaluated in 52 healthy older adults and 51 younger adults using two common data analytic approaches: independent component analysis and seed-based functional connectivity (seed at bilateral M1 and S1). We then evaluated whether the altered rsFC of the SM network could delineate trajectories of the age of older adults using a machine learning methodology. Compared with the younger adults, the older demonstrated reduced functional integration with increasing age in the mid-posterior insula of SM network and increased rsFC among the sensorimotor cortex. Moreover, the reduction in the rsFC of mid-posterior insula is associated with the age of older adults. Critically, the analysis based on two-aspect connectivity-based prediction frameworks revealed that the age of older adults could be reliably predicted by this reduced rsFC. These findings further indicated that healthy aging has a marked influence on the SM system that would be associated with a reorganization of SM system with aging. Our findings provide further insight into changes in sensorimotor function in the aging brain.

Detección de anticuerpos antiestreptococos, anti-enolasa y antineurales en sujetos con trastornos psiquiátricos de inicio temprano / Detection of anti-streptococcal, anti-enolase, and anti-neural antibodies in subjects with earlyonset psychiatric disorders

Introducción. La infección por Estreptococo del grupo A puede ocasionar secuelas post-infecciosas entre las que se han reportado un espectro de trastornos obsesivos-compulsivos y tics de aparición en la edad pediátrica y origen autoinmune (PANDAS). No ha sido diseñada una prueba inmunológica que permita diagnosticar inequívocamente estos trastornos. En este trabajo se evaluó la detección en suero de anticuerpos contra Enolasa cerebral humana (AE), tejido neural (AN) y Estreptococo (AS) como herramienta de laboratorio para el diagnóstico de trastornos psiquiátricos de inicio temprano. Metodología. Los anticuerpos séricos contra Enolasa cerebral humana, proteínas totales del Estreptococo y proteínas totales cerebrales fueron detectados mediante la metodología de ELISA en 37 individuos con diagnóstico presuntivo de PANDAS y en 12 sujetos sanos de México y Cuba. Resultados. Los títulos de anticuerpos contra AE y AS fueron más elevados en el grupo de pacientes vs controles (t-student, tAE=-2.17, P=0.035; tAS=-2.68, P=0.01, n=12 y 37/grupo, gl=47, nivel de significación de 0.05), mientras que los títulos de anticuerpos AN no difirieron entre ambos grupos (P(t)=0.05). La seropositividad (títulos > mediacontrol + IC95) simultánea a los tres anticuerpos fue mayor (51.4 %) en los individuos del grupo de los pacientes comparado con los controles (8.3%) (X2 =5.27, P=0.022, gl=1, n=49). Conclusiones. La detección simultánea de los tres anticuerpos séricos podría brindar información útil para el diagnóstico etiológico de los individuos con trastorno obsesivo compulsivo de inicio temprano asociados con la infección por Estreptococo y en consecuencia para indicar una terapéutica adecuada

Introduction. Infection with group A Streptococcus (Strep A) can cause post-infectious sequelae, including a spectrum of childhood-onset obsessive-compulsive (OCD) and tic disorders with autoimmune origin (PANDAS, Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections). Until now, no single immunological test has been designed that unequivocally diagnoses these disorders. In this study, we assessed the detection of serum antibodies against human brain enolase (AE), neural tissue (AN) and Streptococcus (AS) as a laboratory tool for the diagnosis of early-onset psychiatric disorders. Methodology. Serum antibodies against human brain enolase, total brain proteins, and total proteins from StrepA were detected by ELISA in 37 patients with a presumptive diagnosis of PANDAS and in 12 healthy subjects from Mexico and Cuba. Results. The antibody titers against human brain enolase (AE) and Streptococcal proteins (AS) were higher in patients than in control subjects (t-student, tAE=-2.17, P=0.035; tAS=-2.68, P=0.01, n=12 and 37/group, df=47, significance level 0.05), while the neural antibody titers did not differ between the two groups (P(t)=0.05). The number of subjects (titers> mean control + CI95) with simultaneous seropositivity to all three antibodies was higher in the patient group (51.4%) than in the control group (8.3%) group (X2 =5.27, P=0.022, df=1, n=49). Conclusions. The simultaneous detection of all three of these antibodies could provide valuable information for the etiologic diagnosis of individuals with early-onset obsessive compulsive disorders associated with streptococcal infection and, consequently, for prescribing suitable therapy

Detection of anti-streptococcal, antienolase, and anti-neural antibodies in subjects with early-onset psychiatric disorders.

INTRODUCTION: Infection with group A Streptococcus (StrepA) can cause post-infectious sequelae, including a spectrum of childhood-onset obsessive-compulsive (OCD) and tic disorders with autoimmune origin (PANDAS, Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections). Until now, no single immunological test has been designed that unequivocally diagnoses these disorders. In this study, we assessed the detection of serum antibodies against human brain enolase (AE), neural tissue (AN) and Streptococcus (AS) as a laboratory tool for the diagnosis of early-onset psychiatric disorders. METHODOLOGY: Serum antibodies against human brain enolase, total brain proteins, and total proteins from StrepA were detected by ELISA in 37 patients with a presumptive diagnosis of PANDAS and in 12 healthy subjects from Mexico and Cuba. RESULTS: The antibody titers against human brain enolase (AE) and Streptococcal proteins (AS) were higher in patients than in control subjects (t-student, tAE=-2.17, P=0.035; tAS=-2.68, P=0.01, n=12 and 37/group, df=47, significance level 0.05), while the neural antibody titers did not differ between the two groups (P(t)=0.05). The number of subjects (titers> meancontrol + CI95) with simultaneous seropositivity to all three antibodies was higher in the patient group (51.4%) than in the control group (8.3%) group (X2=5.27, P=0.022, df=1, n=49). CONCLUSIONS: The simultaneous detection of all three of these antibodies could provide valuable information for the etiologic diagnosis of individuals with early-onset obsessive-compulsive disorders associated with streptococcal infection and, consequently, for prescribing suitable therapy.

Timing and tuning for familiarity of cortical responses to faces.

Different kinds of known faces activate brain areas to dissimilar degrees. However, the tuning to type of knowledge, and the temporal course of activation, of each area have not been well characterized. Here we measured, with functional magnetic resonance imaging, brain activity elicited by unfamiliar, visually familiar, and personally-familiar faces. We assessed response amplitude and duration using flexible hemodynamic response functions, as well as the tuning to face type, of regions within the face processing system. Core face processing areas (occipital and fusiform face areas) responded to all types of faces with only small differences in amplitude and duration. In contrast, most areas of the extended face processing system (medial orbito-frontal, anterior and posterior cingulate) had weak responses to unfamiliar and visually-familiar faces, but were highly tuned and exhibited prolonged responses to personally-familiar faces. This indicates that the neural processing of different types of familiar faces not only differs in degree, but is probably mediated by qualitatively distinct mechanisms.

Linkage of functional and structural anomalies in the left amygdala of reactive-aggressive men.

Amygdala structural and functional abnormalities have been associated to reactive aggression in previous studies. However, the possible linkage of these two types of anomalies has not been examined. We hypothesized that they would coincide in the same localizations, would be correlated in intensity and would be mediated by reactive aggression personality traits. Here violent (n = 25) and non-violent (n = 29) men were recruited on the basis of their reactive aggression. Callous-unemotional (CU) traits were also assessed. Gray matter concentration (gmC) and reactivity to fearful and neutral facial expressions were measured in dorsal and ventral amygdala partitions. The difference between responses to fearful and neutral facial expressions was calculated (F/N-difference). Violent individuals exhibited a smaller F/N-difference and gmC in the left dorsal amygdala, where a significant coincidence was found in a conjunction analysis. Moreover, the left amygdala F/N-difference and gmC were correlated to each other, an effect mediated by reactive aggression but not by CU. The F/N-difference was caused by increased reactivity to neutral faces. This suggests that anatomical anomalies within local circuitry (and not only altered input) may underlie the amygdala hyper-reactivity to social signals which is characteristic of reactive aggression.

Covert face recognition without the fusiform-temporal pathways.

Patients with prosopagnosia are unable to recognize faces consciously, but when tested indirectly they can reveal residual identification abilities. The neural circuitry underlying this covert recognition is still unknown. One candidate for this function is the partial survival of a pathway linking the fusiform face area (FFA) and anterior-inferior temporal (AIT) cortex, which has been shown to be essential for conscious face identification. Here we performed functional magnetic, and diffusion tensor imaging in FE, a patient with severe prosopagnosia, with the goal of identifying the neural substrates of his robust covert face recognition. FE presented massive bilateral lesions in the fusiform gyri that eliminated both FFAs, and also disrupted the fibers within the inferior longitudinal fasciculi that link the visual areas with the AITs and medial temporal lobes. Therefore participation of the fusiform-temporal pathway in his covert recognition was precluded. However, face-selective activations were found bilaterally in his occipital gyri and in his extended face system (posterior cingulate and orbitofrontal areas), the latter with larger responses for previously-known faces than for faces of strangers. In the right hemisphere, these surviving face selective-areas were connected via a partially persevered inferior fronto-occipital fasciculus. This suggests an alternative occipito-frontal pathway, absent from current models of face processing, that could explain the patient's covert recognition while also playing a role in unconscious processing during normal cognition.

ERP generator anomalies in presymptomatic carriers of the Alzheimer's disease E280A PS-1 mutation.

Although subtle anatomical anomalies long precede the onset of clinical symptoms in Alzheimer's disease, their impact on the reorganization of brain networks underlying cognitive functions has not been fully explored. A unique window into this reorganization is provided by presymptomatic cases of familial Alzheimer's disease (FAD). Here we studied neural circuitry related to semantic processing in presymptomatic FAD cases by estimating the intracranial sources of the N400 event-related potential (ERP). ERPs were obtained during a semantic-matching task from 24 presymptomatic carriers and 25 symptomatic carriers of the E280A presenilin-1 (PS-1) mutation, as well as 27 noncarriers (from the same families). As expected, the symptomatic-carrier group performed worse in the matching task and had lower N400 amplitudes than both asymptomatic groups, which did not differ from each other on these variables. However, N400 topography differed in mutation carrier groups with respect to the noncarriers. Intracranial source analysis evinced that the presymptomatic-carriers presented a decrease of N400 generator strength in right inferior-temporal and medial cingulate areas and increased generator strength in the left hippocampus and parahippocampus compared to the controls. This represents alterations in neural function without translation into behavioral impairments. Compared to controls, the symptomatic-carriers presented a similar anatomical shift in the distribution of N400 generators to that found in presymptomatic-carriers, albeit with a larger reduction in generator strength. The redistribution of N400 generators in presymptomatic-carriers indicates that early focal degeneration associated with the mutation induces neural reorganization, possibly contributing to a functional compensation that enables normal performance in the semantic task.

Brain potentials reflect access to visual and emotional memories for faces.

Familiar faces convey different types of information, unlocking memories related to social-emotional significance. Here, the availability over time of different types of memory was evaluated using the time-course of P3 event related potentials. Two oddball paradigms were employed, both using unfamiliar faces as standards. The infrequent targets were, respectively, artificially-learned faces (devoid of social-emotional content) and faces of acquaintances. Although in both tasks targets were detected accurately, the corresponding time-course and scalp distribution of the P3 responses differed. Artificially-learned and acquaintance faces both elicited a P3b, maximal over centro-parietal sites, and a latency of 500ms. Faces of acquaintances elicited an additional component, an early P3 maximal over frontal sites: with a latency of 350ms. This suggests that visual familiarity can only trigger the overt recognition processes leading to the slower P3b, whereas emotional-social information can also elicit fast and automatic assessments (indexed by the frontal-P3) crucial for successful social interactions.

Covert matching of unfamiliar faces in a case of prosopagnosia: an ERP study.

In addition to their deficit in overt face recognition, patients with prosopagnosia also have difficulties in matching sequentially presented unfamiliar faces. Here we assessed the possibility that covert matching of faces was present in a case with prosopagnosia using event-related potentials (ERPs). The participants (patient FE and normal controls) were challenged with a face-identity matching task, in which they decided whether two sequentially presented photographs of unfamiliar faces represented the same person. Only internal face features were used and the two faces in a pair differed in emotional expression. FE failed to overtly match these stimuli. In contrast, the ERPs revealed evidence of covert matching. If the two faces within a pair of stimuli depicted different posers, then the response to the second face contained an enhanced N300 compared to the situation where the identity of the faces was the same. The latency of the N300 was the same as a similar component found in controls. These results suggest that some cases with prosopagnosia have a covert ability to match unfamiliar faces, with similar temporal dynamics as controls, which in contrast with the idea that a generalized slowing of face processing occurs in all cases of prosopagnosia.

Evaluación electrofisiológica de la memoria semántica en la enfermedad de Alzheimer / Electrophysiological assessment of semantic memory in Alzheimer's disease

El presente estudio utilizó la técnica de los Potenciales Relacionados a Eventos (PREs) para analizar la actividad eléctrica cerebral de un grupo de diez pacientes con enfermedad de Alzheimer (EA) y un grupo de 10 ancianos asintomáticos ante una prueba de categorización semántica. La tarea se conformó de 118 parejas de dibujos de objetos y animales comunes. El 50 por ciento de las parejas pertenecían a un mismo grupo supraordinado y constituía la condición congruente (ej. guitarra-violín), el otro 50 por ciento pertenecía a diferentes grupos supraordinados y constituía la condición incongruente (ej. casco-violín). Al comparar los PREs de ambos grupos, se observó una reducción significativa del componente N400 en los pacientes con EA. Esta reducción se debió a una pronunciada positividad de la actividad eléctrica cerebral ante la condición incongruente. La disminución del N400 en los PREs de los pacientes con EA apoya la hipótesis sobre la existencia de dificultades para acceder y utilizar la información semántica de manera eficiente