Cerebral networks of sustained attention and working memory: a functional magnetic resonance imaging study based on the Continuous Performance Test.

INTRODUCTION: One of the most used paradigms in the study of attention is the Continuous Performance Test (CPT). The identical pairs version (CPT-IP) has been widely used to evaluate attention deficits in developmental, neurological and psychiatric disorders. However, the specific locations and the relative distribution of brain activation in networks identified with functional imaging, varies significantly with differences in task design. AIM: To design a task to evaluate sustained attention using functional magnetic resonance imaging (fMRI), and thus to provide data for research concerned with the role of these functions. SUBJECTS AND METHODS: Forty right-handed, healthy students (50% women; age range: 18-25 years) were recruited. A CPT-IP implemented as a block design was used to assess sustained attention during the fMRI session. RESULTS: The behavioural results from the CPT-IP task showed a good performance in all subjects, higher than 80% of hits. fMRI results showed that the used CPT-IP task activates a network of frontal, parietal and occipital areas, and that these are related to executive and attentional functions. CONCLUSIONS: In relation to the use of the CPT to study of attention and working memory, this task provides normative data in healthy adults, and it could be useful to evaluate disorders which have attentional and working memory deficits.

TITLE: Bases cerebrales de la atencion sostenida y la memoria de trabajo: un estudio de resonancia magnetica funcional basado en el Continuous Performance Test.Introduccion. Uno de los paradigmas mas utilizados en el estudio de la atencion es el Continuous Performance Test (CPT). La version de pares identicos (CPT-IP) se ha utilizado ampliamente para evaluar los deficits de atencion en los trastornos del neurodesarrollo, neurologicos y psiquiatricos. Sin embargo, la localizacion de la activacion cerebral de las redes atencionales varia significativamente segun el diseño de resonancia magnetica funcional (RMf) usado. Objetivo. Diseñar una tarea para evaluar la atencion sostenida y la memoria de trabajo mediante RMf para proporcionar datos de investigacion relacionados con la localizacion y el papel de estas funciones. Sujetos y metodos. El estudio conto con la participacion de 40 estudiantes, todos ellos diestros (50%, mujeres; rango: 18-25 años). La tarea de CPT-IP se diseño como una tarea de bloques, en la que se combinaban los periodos CPT-IP con los de reposo. Resultados. La tarea de CPT-IP utilizada activa una red formada por regiones frontales, parietales y occipitales, y estas se relacionan con funciones ejecutivas y atencionales. Conclusiones. La tarea de CPT-IP utilizada en nuestro trabajo proporciona datos normativos en adultos sanos para el estudio del sustrato neural de la atencion sostenida y la memoria de trabajo. Estos datos podrian ser utiles para evaluar trastornos que cursan con deficits en memoria de trabajo y en atencion sostenida.

Cerebral correlates of declarative memory dysfunctions in early traumatic brain injury.

We investigated residual brain damage in subjects who suffered severe traumatic brain injury (TBI) in childhood, and its relationship with declarative memory impairment. Magnetic resonance imaging (MRI) volumetric data and memory performance were compared between 16 adolescents with antecedents of severe TBI and 16 matched normal controls. Volumes of grey matter, white matter, cerebrospinal fluid (CSF), hippocampus, and caudate nuclei were measured. Verbal memory was assessed by the Rey's Auditory Verbal Learning test and visual memory by the Rey's Complex Figure. TBI patients performed significantly worse than controls in both verbal and visual memory. Patients presented decreased white matter volume and increased CSF. The hippocampus was reduced, but not the caudate nuclei. Memory performance correlated with CSF. Plasticity is incomplete for structural and functional deficits in children with TBI. Hippocampal atrophy, white matter loss, and memory impairment remain until adolescence. Memory sequelae are related more to diffuse brain injury, as reflected by MRI findings of increased CSF, than to hippocampal injury.

Apolipoproteins E and C1 and brain morphology in memory impaired elders.

Previous research has shown that polymorphisms of the apolipoproteins E ( APOE) and APOC1 represent genetic risk factors for dementia and for cognitive impairment in the elderly. The brain mechanisms by which these genetic variations affect behavior or clinical severity are poorly understood. We studied the effect of APOE and APOC1 genes on magnetic resonance imaging measures in a sample of 50 subjects with age-associated memory impairment. The APOE E4 allele was associated with reduced left hippocampal volumes and APOE*E3 status was associated with greater frontal lobe white matter volumes. However, no APOE effects were observed when analyses accounted for other potential confounding variables. The effects of APOC1 on hippocampal volumes appeared to be more robust than those of the APOE polymorphism. However, no modulatory effects on brain morphology outside the medial temporal lobe region were observed when demographic variables, clinical status, and other anatomical brain measurements were taken into consideration. Our results suggest that the role of the APOC1 polymorphism in brain morphology of the cognitively impaired elderly should be examined in further studies.

[Evaluation of diffuse cerebral atrophy in patients with a history of traumatic brain injury and its relation to cognitive deterioration]. / Evaluación de la atrofia cerebral difusa en pacientes con antecedentes de traumatismo craneoencefálico y su relación con el deterioro cognitivo.

INTRODUCTION: Diffuse damage secondary to traumatic brain injury (TBI) can be studied through volumetric analysis of several structures that are sensible to this kind of injury, such as corpus callosum, ventricular system, hippocampus, basal ganglia and the volume of cerebrospinal fluid spaces. OBJECTIVE: Our aim is to describe how closed head injury (CHI) occurred in early years produce diffuse damage, and how this damage affects general cognitive functioning at long term. PATIENTS AND METHODS: Initially the group of subjects was composed of 27 head injured children and adolescents following paediatric moderate to severe TBI. From this initial group we selected 15 patients without focal lesion, or in case of having suffered focal lesion, this was smaller than 2,600 mm3. These subjects were assessed by means of volumetric analysis of cerebrospinal fluid spaces, corpus callosum, hippocampus and caudate nucleus, comparing the results with a matched control group. We calculated the degree of general cognitive ability of these subjects through tests of intellectual, memory, frontal lobe and motor speed functioning. RESULTS: This study demonstrates that early CHI produce a volume decrease in all measured structures. Corpus callosum atrophy is the factor that better explains general cognitive impairment. CONCLUSIONS: Diffuse damage secondary to moderate to severe peadiatric TBI has long term effects on several cerebral structures and on cognitive performance. Corpus callosum atrophy is the best predictor for general cognitive impairment, compared with other affected structures.

Evaluación de la atrofia cerebral difusa en pacientes con antecedentes de traumatismo craneoencefálico y su relación con el deterioro cognitivo / Evaluationo of diffuse cerebral atrophy in patients with a history of traumatic brain injury and its relation to cognitive deterioration

Introducción. El daño cerebral difuso (DCD) secundario al traumatismo craneoencefálico (TCE) puede estudiarse a través de la evaluación volumétrica de diversas estructuras, entre las cuales destacan el cuerpo calloso, el hipocampo y los ganglios basales. Asimismo, el volumen de líquido cefalorraquídeo es también una buena medida de pérdida de masa encefálica. Objetivo. Evaluar el DCD producido por un TCE cerrado infantil y observar los efectos que éste tiene a largo plazo sobre el rendimiento cognitivo general. Pacientes y métodos. Se partió inicialmente de una muestra de 27 pacientes con TCE cerrado infantil, moderado o grave, de la cual se seleccionaron 15 sujetos, por carecer de lesiones focales, o en su caso, que éstas fueran inferiores a 2.600 mm3. En los 15 sujetos estudiados se realizó un análisis volumétrico del líquido cefalorraquídeo, del cuerpo calloso, del hipocampo y del núcleo caudado y se comparó con un grupo control. Además, se evaluó su deterioro cognitivo general mediante test de inteligencia, de memoria, y de la evaluación de las funciones frontales y motoras. Resultados. Los resultados mostraron que los pacientes con antecedentes de traumatismo presentaban atrofia en todas las estructuras medidas y que la atrofia del cuerpo calloso fue la variable que mejor explicaba el deterioro cognitivo general. Conclusiones. El daño difuso causado por TCE moderado-grave en la infancia persiste a largo plazo y comporta déficit cognitivos; la atrofia del cuerpo calloso es la que mejor predice el deterioro cognitivo general de los afectados, con relación a otras estructuras indicadoras de DCD (AU)

Técnicas morfométricas para el análisis deestructuras cerebrales de imágenes de resonanciamagnética: aplicaciones en psiquiatría / Morphometric techniques for the analysis of cerebral structures from magnetic resonance imaging scans: applications in psychiatry

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[Auditory evoked potentials and alcohol: characteristics of the mismatch negativity component in alcoholism]. / Potenciales evocados auditivos y alcohol: características del componente mismatch negativity en el alcoholismo.

AIMS: The aim of this work is to review the effects of alcohol on the MMN component, to discuss its viability as a vulnerability marker for alcoholism, and to link it with the P300 component. METHOD: Alcohol alters the P300 and MMN components of auditory evoked potentials. In alcoholism, the alterations observed in the P300 component in risk subjects have been seen as markers of susceptibility to development of the illness. In the case of the MMN component, on the other hand, to date its viability as a vulnerability marker has only been evaluated in three studies, with varying results. While two of them found no differences, in the third and most recent it was found that risk subjects presented an increase in the amplitude of the MMN, which was interpreted as a reflection of the cortical hyperexcitability suggested by other authors and which was also reflected in the decrease in the P300 amplitude. CONCLUSIONS: The results obtained do not enable us to draw conclusions about whether the MMN component is altered in risk subjects for alcoholism. The differences in the studies that have been conducted could be due to the variations in the characteristics of the samples used or of the evaluation of the characteristics of MMN. The analysis of previous work on P300 or MMN suggests that broader, more homogeneous samples should be used in future research and that, in addition to the MMN peak, its mean amplitude in successive intervals, together with its two subcomponents should also be evaluated separately.

Potenciales evocados auditivos y alcohol: característicasdel componente mismatch negativity en el alcoholismo / Auditory evoked potentials and alcohol: characteristics of the mismatch negativity component in alcoholism

Objetivo. Revisar los efectos del alcohol sobre el componente MMN (del inglés mismatch negativity), discutir acerca de su viabilidad como marcador de vulnerabilidad del alcoholismo y relacionarlo con el componente P300. Desarrollo. El alcohol altera los componentes P300 y MMN de los potenciales evocados auditivos. En el alcoholismo, las alteraciones observadas en el componente P300 en sujetos de riesgo se han considerado como marcadores de susceptibilidad al desarrollo de la enfermedad. En el caso del componente MMN, en cambio, hasta la actualidad, únicamente se ha evaluado su viabilidad como marcador de vulnerabilidad en tres trabajos, y los resultados son dispares. Mientras que dos de ellos no observan diferencias, en el tercero, y más reciente, se constata que los sujetos de riesgo presentan un aumento de la amplitud de MMN, interpretada como reflejo de la hiperexcitabilidad cortical sugerida por otros autores y reflejada también en la disminución de la amplitud de P300. Conclusiones. Los resultados obtenidos no permiten sacar conclusiones sobre si el componente MMN se altera en sujetos de riesgo para el alcoholismo. Las diferencias en los trabajos realizados podrían deberse a las dispares características de las muestras utilizadas o de la evaluación de las características de MMN. El análisis de los trabajos previos sobre P300 y MMN sugiere que en estudios futuros se deberían utilizar muestras más amplias y homogéneas, y se debería evaluar, además del pico de MMN, su amplitud media en intervalos sucesivos, así como sus dos subcomponentes por separado (AU)

[The potential P300 in the evaluation of the side effects of dexchlorpheniramine]. / El potencial P300 en la valoracion de los efectos secundarios de la dexclorfeniramina.

INTRODUCTION: The antihistamine chlorpheniramine presents multiple adverse side effects on the central nervous system. In earlier work it has been observed that a dose equal to the one used in this study alters the evoked potentials PN (processing negativity) and MMN (mismatch negativity), which are, respectively, indicators of selective attention and of an automatic mechanism for detecting changes in auditory stimulation. AIMS. The aim of the present study was to evaluate the effects of a single 4 mg dose of dexchlorpheniramine on the evoked potential P300, to enable us to better define its effects on the central nervous system. Subjects and methods. Using the double blind procedure, half a sample consisting in 20 subjects was administered 4 mg of dexchlorpheniramine and the other 10 received placebo. 150 minutes after ingestion the potential P300 was recorded using an active oddball paradigm. Likewise, efficiency in detecting target stimuli was also evaluated. RESULTS: results show that a single 4 mg dose of dexchlorpheniramine does not alter P300 nor efficiency in detecting target stimuli. CONCLUSIONS: Results show that the dose used has no effect on voluntary processes involving the categorization of target stimuli nor on their detection. However, the alteration of other attentional mechanisms observed in previous work using the same doses suggests that it would be advisable to employ different evoked potential paradigms in the evaluation of the side effects other active principles or psychoactive substances have on auditory attention.

El potencial P300 en la valoraciónde los efectos secundarios de la dexclorfeniramina / The potential p300 in the evaluation of the side effects of dexchlorpheniramine

Introducción. El antihistamínico clorfeniramina presenta múltiples efectos secundarios adversos sobre el sistema nervioso central. Previamente se ha observado que una dosis igual a la utilizada en el presente estudio altera los potenciales evocados PN ( processing negativity) y MMN (mismatch negativity), indicadores respectivamente de la atención selectiva y de un mecanismo automático de detección de cambios en la estimulación auditiva. Objetivo. El objetivo del presente estudio es evaluar los efectos de una dosis única de 4 mg de dexclorfeniramina sobre el potencial evocado P300, a fin de delimitar mejor los efectos de dicha sustancia sobre el sistema nervioso central. Sujetos y métodos. Muestra formada por 20 sujetos, mediante un procedimiento de doble ciego la mitad de ellos recibió 4 mg de dexclorfeniramina y la otra mitad placebo. Al cabo de 150 minutos de la ingestión, se registró el potencial P300 mediante un paradigma de oddball activo. Asimismo, se evaluó el rendimiento en la detección de los estímulos designados ( target). Resultados. Los resultados indican que una dosis única de 4 mg de dexclorfeniramina no altera el P300 ni el rendimiento en la tarea de detección de estímulos designados. Conclusiones. Si bien los resultados indican que la dosis utilizada no afecta a los procesos voluntarios de categorización de los estímulos designados ni a su detección, la alteración de otros mecanismos atencionales observada en trabajos previos utilizando la misma dosis sugiere la idoneidad de emplear diferentes paradigmas de potenciales evocados en la evaluación de los efectos secundarios sobre la atención auditiva de otros principios activos o sustancias psicoactivas (AU)

[The secondary effects of the antihistamine chlorpheniramine on the central nervous system]. / Efectos secundarios del antihistamánico clorfeniramina sobre el sistema nervioso central.

OBJECTIVE: The objective of this study is to review the main investigations into the secondary effects of the antihistamine chlorpheniramine on the central nervous system (CNS). DEVELOPMENT: The antagonists of the H1 receptors of histamine, usually used in the treatment of symptoms of allergy or the common cold, have many adverse effects on the CNS. They cause day time drowsiness, cause poorer performance of tasks involving visuo motor coordination and make it more difficult to detect target auditory stimuli in tasks involving sustained concentration. When using evoked potentials (EP) it has been observed that they alter the system for maintaining auditory attention. They cause increased P300 latency, an EP related to the voluntary ability to discriminate between relevant stimuli, a reduction in the amplitude of mismatch negativity (MMN), an EP which is seen as a pre attention mechanism for automatic detection of environmental acoustic changes and alters selective attention capacity, reflected by a reduction in the amplitude of processing negativity (PN). CONCLUSIONS: These studies show that chlorpheniramine has major adverse effects on the CNS, and the patient may not be subjectively aware of this (e.g. selective attention). This means that in certain situations it is a dangerous substance. The characteristics of these adverse effects should lead to a review of the prescription of chlorpheniramine, and stimulate the search for other substances with similar therapeutic actions but fewer side effects on the CNS.

Efectos secundarios del antihistamínico clorfeniramina sobre el sistema nervioso central / The secondary effects of the antihistamine chlorpheniramine on the central nervous system

Objetivo. El objetivo del presente trabajo es revisar las principales investigaciones centradas en la evaluación de los efectos secundarios del antihistamínico clorfeniramina sobre el sistema nervioso central (SNC). Desarrollo. Los antagonistas de los receptores H1 de la histamina, usados habitualmente en el tratamiento de los síntomas de alergias y resfriados, presentan múltiples efectos secundarios adversos sobre el SNC. Causan somnolencia diurna, disminuyen el rendimiento en tareas de coordinación visuomotora y dificultan la detección de estímulos target auditivos en tareas de atención sostenida. Además, mediante la utilización de potenciales evocados (PE), se ha observado que la histamina altera el sistema atencional auditivo. Provoca un aumento de la latencia de P300, un PE relacionado con la capacidad voluntaria de discriminación de los estímulos relevantes, una disminución de la amplitud de MMN (mismatch negativity), un PE que refleja un mecanismo preatencional de detección automática de los cambios acústicos en el entorno, y altera la capacidad de atención selectiva, reflejada en una disminución de la amplitud de PN (processing negativity). Conclusiones. Los estudios realizados han puesto de relieve que la clorfeniramina presenta importantes efectos secundarios en el SNC, algunos sin que el sujeto tenga indicadores subjetivos de ello (p. ej., atención selectiva); ello la convierte en una sustancia de riesgo en determinadas situaciones. Las características de estos efectos adversos deben servir para revisar la prescripción de la clorfeniramina y para estimular la búsqueda de otras sustancias con iguales efectos terapéuticos y menores efectos secundarios sobre el SNC (AU)

[Study of the long term sequelae of traumatic brain injury: evaluation of declarative and procedural memory, and its neuroanatomic substrate]. / Estudio de las secuelas a largo plazo de los traumatismos craneoencefálicos: evaluación de la memoria declarativa y procedimental y de su sustrato neuroanatómico.

INTRODUCTION AND OBJECTIVES: The hippocampus and the striatum have been proposed as respectively cerebral substrates of declarative and procedural memory. Both structures are vulnerable to traumatic brain injury. Although declarative and procedural memory have been reported to be impaired in traumatic brain injury (TBI), volumetric measures have so far failed to associate this impairment with atrophy of hippocampal and striatal structures. In our study, we investigated the profile of declarative and procedural memory in children who suffered from moderate to severe traumatic brain injury during childhood (injury test interval: 9.42+/-1.98 years). PATIENTS AND METHODS: Nineteen patients and matched controls were evaluated on tests of declarative memory and motor learning. Results showed that TBI subjects exhibit poorer performance in both tasks. Moreover, structural magnetic resonance images were obtained from TBI subjects. In order to relate neuropsychological performance with hippocampal and neostriatal volumetric data, correlation analyses were performed. RESULTS: Significant positive correlations were obtained between hippocampal volume and memory for objects. Striatal volume correlated positively with motor learning and with verbal memory. CONCLUSIONS: It thus seems that plasticity does not completely compensate for the memory deficits resultant from neural loss in the immature brain.

Estudio de las secuelas a largo plazo de los traumatismos craneoencefálicos: evaluación de la memoria declarativay procedimental y de su sustrato neuroanatómico / Study of the long term sequelae of traumatic brain injury: evaluation of declarative and procedural memory, and its neuroanatomic substrate

Introducción y objectivos. Los estudios realizados hasta la actualidad permiten considerar el hipocampo y el estriado como el sustrato neural de las memorias declarativa y procedimental, respectivamente. Si bien ambas estructuras son vulnerables al traumatismo craneoencefálico, y diversos estudios han observado que tanto la memoria declarativa como la procedimental también decaen a consecuencia de traumatismo craneoencefálico, los estudios volumétricos realizados hasta ahora no muestran evidencia de la relación entre la atrofia de ambas estructuras y el grado de alteración de la memoria. El presente estudio se centra en investigar el grado de alteración de las memorias declarativa y procedimental en niños que, de pequeños, sufrieron traumatismo craneoencefálico de moderado a grave. Pacientes y métodos. Diecinueve pacientes y sus respectivos controles fueron evaluados en tareas de memoria declarativa y aprendizaje motor. Los resultados mostraron que los sujetos con traumatismo craneoencefálico exhibían un peor rendimiento en ambas tareas. Además, para relacionar el rendimiento neuropsicológico con los datos volumétricos del hipocampo y el estriado, se realizaron análisis de correlaciones. Resultados. Se encontraron correlaciones positivas entre el volumen del hipocampo y la memoria para objetos del test `objeto-localización'. Por su parte, el volumen del estriado correlacionaba positivamente con el aprendizaje motor y la memoria verbal. Conclusión. Los resultados obtenidos sugieren que los mecanismos de plasticidad no compensan completamente los déficit de memoria resultantes de la pérdida neural en el cerebro immaduro (AU)

MRI and genetic correlates of cognitive function in elders with memory impairment.

The present study investigated the relationship between genetic variation, MRI measurements and neuropsychological function in a sample of 58 elders exhibiting memory decline. In agreement with previous reports, we found that the epsilon4 allele of the apolipoprotein E (APOE) and the D allele of the angiotensin converting enzyme (ACE) polymorphisms negatively modulated the cognitive performance. Further, we found an association between the A allele of the apolipoprotein C1 (APOC1) polymorphism and poorer memory and frontal lobe function. No clear associations emerged between MRI measures of white matter lesions (WML) or hippocampal sulcal cavities (HSC) and the cognitive performance after controlling for age effects. Further, the degree of WML or HSC lesions was in general not predisposed genetically except for the presence of the A allele of the APOC1 polymorphism that was related to a higher severity of HSC scores. Our results suggest that WML or HSC do not represent important brain correlates of genetic influences on cognitive performance in memory impaired subjects.

The H1-receptor antagonist dextro-chlorpheniramine impairs selective auditory attention in the absence of subjective awareness of this impairment.

Although previous studies have shown that the human attention system is partially affected by chlorpheniramine, the effects of chlorpheniramine on human auditory selective attention have not yet been explored. This study examines the effects of a single dose of 4 mg of dextro-chlorpheniramine on human auditory selective attention by means of the evaluation of the event-related brain potential (ERP) processing negativity (PN). The study sample consisted of 20 healthy male humans, who received either a single 4-mg dose of dextro-chlorpheniramine or a placebo in a double-blind design. The subjects were given a dichotic listening task, in which they were instructed to press a response button upon detecting deviant tones (target) while their ERPs were recorded. In parallel, subjective tests evaluated the daytime sleepiness, overall vigor, and affect of the subjects. Results showed that the auditory selective attention is impaired under the effects of chlorpheniramine, as reflected by an attenuation of PN amplitude and by a decrease of performance in the group of subjects who took a single 4-mg dose of dextro-chlorpheniramine. No subjective change in the daytime sleepiness, overall vigor, or affect of the subjects was observed. This lack of conscious awareness of the side effects may lead to situations of risk in tasks for which auditory information is important, because no subjective indicators of attention impairment are available to the subjects.