When the Locus Coeruleus Speaks Up in Sleep: Recent Insights, Emerging Perspectives.

For decades, numerous seminal studies have built our understanding of the locus coeruleus (LC), the vertebrate brain's principal noradrenergic system. Containing a numerically small but broadly efferent cell population, the LC provides brain-wide noradrenergic modulation that optimizes network function in the context of attentive and flexible interaction with the sensory environment. This review turns attention to the LC's roles during sleep. We show that these roles go beyond down-scaled versions of the ones in wakefulness. Novel dynamic assessments of noradrenaline signaling and LC activity uncover a rich diversity of activity patterns that establish the LC as an integral portion of sleep regulation and function. The LC could be involved in beneficial functions for the sleeping brain, and even minute alterations in its functionality may prove quintessential in sleep disorders.

The lactate receptor HCAR1: A key modulator of epileptic seizure activity.

Epilepsy affects millions globally with a significant portion exhibiting pharmacoresistance. Abnormal neuronal activity elevates brain lactate levels, which prompted the exploration of its receptor, the hydroxycarboxylic acid receptor 1 (HCAR1) known to downmodulate neuronal activity in physiological conditions. This study revealed that HCAR1-deficient mice (HCAR1-KO) exhibited lowered seizure thresholds, and increased severity and duration compared to wild-type mice. Hippocampal and whole-brain electrographic seizure analyses revealed increased seizure severity in HCAR1-KO mice, supported by time-frequency analysis. The absence of HCAR1 led to uncontrolled inter-ictal activity in acute hippocampal slices, replicated by lactate dehydrogenase A inhibition indicating that the activation of HCAR1 is closely associated with glycolytic output. However, synthetic HCAR1 agonist administration in an in vivo epilepsy model did not modulate seizures, likely due to endogenous lactate competition. These findings underscore the crucial roles of lactate and HCAR1 in regulating circuit excitability to prevent unregulated neuronal activity and terminate epileptic events.

Homeostatic regulation of REM sleep by the preoptic area of the hypothalamus.

Rapid-eye-movement sleep (REMs) is characterized by activated electroencephalogram (EEG) and muscle atonia, accompanied by vivid dreams. REMs is homeostatically regulated, ensuring that any loss of REMs is compensated by a subsequent increase in its amount. However, the neural mechanisms underlying the homeostatic control of REMs are largely unknown. Here, we show that GABAergic neurons in the preoptic area of the hypothalamus projecting to the tuberomammillary nucleus (POAGAD2→TMN neurons) are crucial for the homeostatic regulation of REMs. POAGAD2→TMN neurons are most active during REMs, and inhibiting them specifically decreases REMs. REMs restriction leads to an increased number and amplitude of calcium transients in POAGAD2→TMN neurons, reflecting the accumulation of REMs pressure. Inhibiting POAGAD2→TMN neurons during REMs restriction blocked the subsequent rebound of REMs. Our findings reveal a hypothalamic circuit whose activity mirrors the buildup of homeostatic REMs pressure during restriction and that is required for the ensuing rebound in REMs.

Homeostatic regulation of rapid eye movement sleep by the preoptic area of the hypothalamus.

Rapid eye movement sleep (REMs) is characterized by activated electroencephalogram (EEG) and muscle atonia, accompanied by vivid dreams. REMs is homeostatically regulated, ensuring that any loss of REMs is compensated by a subsequent increase in its amount. However, the neural mechanisms underlying the homeostatic control of REMs are largely unknown. Here, we show that GABAergic neurons in the preoptic area of the hypothalamus projecting to the tuberomammillary nucleus (POAGAD2→TMN neurons) are crucial for the homeostatic regulation of REMs in mice. POAGAD2→TMN neurons are most active during REMs, and inhibiting them specifically decreases REMs. REMs restriction leads to an increased number and amplitude of calcium transients in POAGAD2→TMN neurons, reflecting the accumulation of REMs pressure. Inhibiting POAGAD2→TMN neurons during REMs restriction blocked the subsequent rebound of REMs. Our findings reveal a hypothalamic circuit whose activity mirrors the buildup of homeostatic REMs pressure during restriction and that is required for the ensuing rebound in REMs.

Response of sleep slow oscillations to acoustic stimulation is evidenced by distinctive synchronization processes.

Closed-loop acoustic stimulation (CLAS) during sleep has shown to boost slow wave (SW) amplitude and spindle power. Moreover, sleep SW have been classified based on different processes of neuronal synchronization. Thus, different types of SW events may have distinct functional roles and be differentially affected by external stimuli. However, the SW synchronization processes affected by CLAS are not well understood. Here, we studied the effect of CLAS on the dissociation of SW events based on two features of neuronal synchronization in the electroencephalogram (topological spread and wave slope). We evaluated and classified individual SW events of 14 healthy subjects during a CLAS stimulated (STM) and a control night (CNT). Three main categories of SW events were found denoting (C1) steep slope SW with global spread, (C2) flat-slope waves with localized spread and homeostatic decline, and (C3) multipeaked flat-slope events with global spread. Comparing between conditions, we found a consistent increase of event proportion and trough amplitudes for C1 events during the time of stimulation. Furthermore, we found similar increases in post-stimulus spectral power in θ, ß, and σ frequencies for CNT vs STIM condition independently of sleep stage or SW categories. However, topological analysis showed differentiated spatial dynamics in N2 and N3 for SW categories and the co-occurrence with spindle events. Our findings support the existence of multiple types of SW with differential response to external stimuli and possible distinct neuronal mechanisms.

Recording of Diurnal Gene Expression in Peripheral Organs of Mice Using the RT-Biolumicorder.

There is high interest in investigating the daily dynamics of gene expression in mammalian organs, for example, in liver. Such studies help to elucidate how and with what kinetics peripheral clocks integrate circadian signals from the suprachiasmatic nucleus, which harbors the circadian master pacemaker, with other systemic and environmental cues, such as those associated with feeding and hormones. Organ sampling around the clock, followed by the analysis of RNA and/or proteins, is the most commonly used procedure in assessing rhythmic gene expression. However, this method requires large cohorts of animals and is only applicable to behaviorally rhythmic animals whose phases are known. Real-time recording of gene expression rhythms using luciferase reporters has emerged as a powerful method to acquire continuous, high-resolution datasets from freely moving individual mice. Here, we share our experience and protocols with this technique, using the RT-Biolumicorder setup.

Noradrenergic circuit control of non-REM sleep substates.

To understand what makes sleep vulnerable in disease, it is useful to look at how wake-promoting mechanisms affect healthy sleep. Wake-promoting neuronal activity is inhibited during non-rapid-eye-movement sleep (NREMS). However, sensory vigilance persists in NREMS in animals and humans, suggesting that wake promotion could remain functional. Here, we demonstrate that consolidated mouse NREMS is a brain state with recurrent fluctuations of the wake-promoting neurotransmitter noradrenaline on the ∼50-s timescale in the thalamus. These fluctuations occurred around mean noradrenaline levels greater than the ones of quiet wakefulness, while noradrenaline (NA) levels declined steeply in REMS. They coincided with a clustering of sleep spindle rhythms in the forebrain and with heart-rate variations, both of which are correlates of sensory arousability. We addressed the origins of these fluctuations by using closed-loop optogenetic locus coeruleus (LC) activation or inhibition timed to moments of low and high spindle activity during NREMS. We could suppress, lock, or entrain sleep-spindle clustering and heart-rate variations, suggesting that both fore- and hindbrain-projecting LC neurons show coordinated infraslow activity variations in natural NREMS. Noradrenergic modulation of thalamic, but not cortical, circuits was required for sleep-spindle clustering and involved NA release into primary sensory and reticular thalamic nuclei that activated both α1- and ß-adrenergic receptors to cause slowly decaying membrane depolarizations. Noradrenergic signaling by LC constitutes a vigilance-promoting mechanism that renders mammalian NREMS vulnerable to disruption on the close-to-minute timescale through sustaining thalamocortical and autonomic sensory arousability. VIDEO ABSTRACT.

Cortico-autonomic local arousals and heightened somatosensory arousability during NREMS of mice in neuropathic pain.

Frequent nightly arousals typical for sleep disorders cause daytime fatigue and present health risks. As such arousals are often short, partial, or occur locally within the brain, reliable characterization in rodent models of sleep disorders and in human patients is challenging. We found that the EEG spectral composition of non-rapid eye movement sleep (NREMS) in healthy mice shows an infraslow (~50 s) interval over which microarousals appear preferentially. NREMS could hence be vulnerable to abnormal arousals on this time scale. Chronic pain is well-known to disrupt sleep. In the spared nerve injury (SNI) mouse model of chronic neuropathic pain, we found more numerous local cortical arousals accompanied by heart rate increases in hindlimb primary somatosensory, but not in prelimbic, cortices, although sleep macroarchitecture appeared unaltered. Closed-loop mechanovibrational stimulation further revealed higher sensory arousability. Chronic pain thus preserved conventional sleep measures but resulted in elevated spontaneous and evoked arousability. We develop a novel moment-to-moment probing of NREMS vulnerability and propose that chronic pain-induced sleep complaints arise from perturbed arousability.

Regulation of Local Sleep by the Thalamic Reticular Nucleus.

In spite of the uniform appearance of sleep as a behavior, the sleeping brain does not produce electrical activities in unison. Different types of brain rhythms arise during sleep and vary between layers, areas, or from one functional system to another. Local heterogeneity of such activities, here referred to as local sleep, overturns fundamental tenets of sleep as a globally regulated state. However, little is still known about the neuronal circuits involved and how they can generate their own specifically-tuned sleep patterns. NREM sleep patterns emerge in the brain from interplay of activity between thalamic and cortical networks. Within this fundamental circuitry, it now turns out that the thalamic reticular nucleus (TRN) acts as a key player in local sleep control. This is based on a marked heterogeneity of the TRN in terms of its cellular and synaptic architecture, which leads to a regional diversity of NREM sleep hallmarks, such as sleep spindles, delta waves and slow oscillations. This provides first evidence for a subcortical circuit as a determinant of cortical local sleep features. Here, we review novel cellular and functional insights supporting TRN heterogeneity and how these elements come together to account for local NREM sleep. We also discuss open questions arising from these studies, focusing on mechanisms of sleep regulation and the role of local sleep in brain plasticity and cognitive functions.

Thalamic reticular control of local sleep in mouse sensory cortex.

Sleep affects brain activity globally, but many cortical sleep waves are spatially confined. Local rhythms serve cortical area-specific sleep needs and functions; however, mechanisms controlling locality are unclear. We identify the thalamic reticular nucleus (TRN) as a source for local, sensory-cortex-specific non-rapid-eye-movement sleep (NREMS) in mouse. Neurons in optogenetically identified sensory TRN sectors showed stronger repetitive burst discharge compared to non-sensory TRN cells due to higher activity of the low-threshold Ca2+ channel CaV3.3. Major NREMS rhythms in sensory but not non-sensory cortical areas were regulated in a CaV3.3-dependent manner. In particular, NREMS in somatosensory cortex was enriched in fast spindles, but switched to delta wave-dominated sleep when CaV3.3 channels were genetically eliminated or somatosensory TRN cells chemogenetically hyperpolarized. Our data indicate a previously unrecognized heterogeneity in a powerful forebrain oscillator that contributes to sensory-cortex-specific and dually regulated NREMS, enabling local sleep regulation according to use- and experience-dependence.

[Differential effects of attention deficit/hyperactivity disorder subtypes in event-related potentials]. / Efecto diferencial del subtipo clínico en los potenciales evocados cognitivos de pacientes con déficit de atención e hiperactividad.

BACKGROUND: To better understand the neurophysiological substrates in attention deficit/hyperactivity disorder (ADHD), a study was performed on of event-related potentials (ERPs) in Colombian patients with inattentive and combined ADHD. METHODS: A case-control, cross-sectional study was designed. The sample was composed of 180 subjects between 5 and 15 years of age (mean, 9.25±2.6), from local schools in Manizales. The sample was divided equally in ADHD or control groups and the subjects were paired by age and gender. The diagnosis was made using the DSM-IV-TR criteria, the Conners and WISC-III test, a psychiatric interview (MINIKID), and a medical evaluation. ERPs were recorded in a visual and auditory passive oddball paradigm. Latency and amplitude of N100, N200 and P300 components for common and rare stimuli were used for statistical comparisons. RESULTS: ADHD subjects show differences in the N200 amplitude and P300 latency in the auditory task. The N200 amplitude was reduced in response to visual stimuli. ADHD subjects with combined symptoms show a delayed P300 in response to auditory stimuli, whereas inattentive subjects exhibited differences in the amplitude of N100 and N200. Combined ADHD patients showed longer N100 latency and smaller N200-P300 amplitude compared to inattentive ADHD subjects. CONCLUSIONS: The results show differences in the event-related potentials between combined and inattentive ADHD subjects.

Efectos de la estimulación eléctrica habenular en la modulación de respuestas emocionales en ratas Wistar / Efeitos da estimulação elétrica habenular na modulação de respostas emocionais em ratos Wistar / Effects of electrical stimulation of the habenula on the modulation of emotional responses in Wistar rats

Resumen A pesar del amplio uso de la estimulación cerebral profunda para controlar patologías neurológicas y neuropsiquiátricas, su mecanismo de acción aún no es claramente conocido, y existen pocos estudios sistemáticos que relacionen la variación de parámetros de estimulación eléctrica (frecuencia, intensidad, duración del pulso) y la ejecución comportamental. La habénula es una estructura reguladora de respuestas emocionales diana en tratamientos para dolor crónico y depresión, pero la relación entre su estimulación crónica y el desempeño animal en pruebas conductuales no se ha establecido con claridad. Con el objetivo de evaluar el efecto emocional de la estimulación habenular crónica, en este estudio se utilizaron ratas Wistar que recibieron estimulación habenular a intensidad baja (10-80 pA) o alta (120-260 pA) y frecuencia baja (80-150 Hz) o alta (240380 Hz): BIBF-AIBF-BIAF-AIAF, durante 15 minutos a lo largo de tres días consecutivos. Al cuarto día, se hizo la evaluación en un laberinto elevado en cruz y en campo abierto. Los resultados indican un efecto de tipo ansiolítico en el tratamiento BIAF, en comparación con BIBF y AIBF (aumento del número de entradas, porcentaje de tiempo en brazos abiertos y de la distancia recorrida en ellos), efecto que no se explica por cambios en la locomotricidad (distancia recorrida en los brazos cerrados y la exploración en el campo abierto). Se concluye que el parámetro frecuencia posee mayor impacto sobre el efecto comportamental que la intensidad -lo que puede explicar algunos hallazgos paradójicos previos-, que los parámetros utilizados no poseen efecto ansiogénico, y que los efectos potencialmente ansiogénicos de la estimulación a baja frecuencia y el papel de los sistemas dopaminérgicos y serotoninérgicos encontrados deben ser estudiados en futuras investigaciones.

Resumo Apesar do amplo uso da estimulação cerebral profunda para controlar patologias neurológicas e neuropsiquiátricas, seu mecanismo de ação ainda não é claramente conhecido e existem poucos estudos sistemáticos que relacionem a variação de parâmetros de estimulação elétrica (frequência, intensidade, duração do pulso) e a execução comportamental. A habênula é uma estrutura reguladora de respostas emocionais específicas em tratamentos para dor crònica e depressão, mas a relação entre sua estimulação crònica e o desempenho animal em testes comportamentais não foi claramente estabelecida. Com o objetivo de avaliar o efeito emocional da estimulação habenular crònica, neste estudo foram utilizados ratos Wistar que receberam estimulação habenular de intensidade baixa (10-80 pA) ou alta (120-260 pA) e frequência baixa (80-150 Hz) ou alta (240-380 Hz): BIBF-AIBF-BIAF-AIAF, durante 15 minutos ao longo de três dias consecutivos. No quarto dia, foi feita a avaliação em um labirinto em cruz elevado e em campo aberto. Os resultados indicam um efeito de tipo ansiolítico no tratamento BIAF, em comparação com BIBF e AIBF (aumento do número de entradas, porcentagem de tempo em braços abertos e da distância percorrida neles), efeito que não se explica por mudanças na locomotividade (distância percorrida nos braços fechados e a exploração no campo aberto). Conclui-se que o parâmetro "frequência" tem mais impacto sobre o efeito comportamental do que a "intensidade" - o que pode explicar algumas descobertas paradoxais prévias -, que os parâmetros utilizados não tenham efeito ansiogênico, e que os efeitos potencialmente ansiogênicos da estimulação de baixa frequência e o papel dos sistemas dopaminérgicos e serotoninérgicos encontrados devem ser estudados em pesquisas futuras.

Abstract Deep brain stimulation is a widely-used approach to the treatment of neurologic and neuropsychiatric diseases. However, its mechanisms remain unclear. There are few systematic studies relating variations on electrical stimulation parameters (frequency, intensity, pulse duration) and behavioral outcome. The habenula relates to emotional behavior and is a main target for chronic pain and depression stimulation treatment. The relation between habenular electrical stimulation and performance in behavioral tests has not been clearly defined. In order to assess the emotional effects of chronic habenular electrical stimulation, Wistar male rats were unilaterally implanted with electrodes aimed to the lateral habenula and assigned to low (10-80 pA) or high (120-260 pA) intensity and low (80-150 Hz) or high (240-380 Hz) frequency conditions: BIBF-AIBF-BIAF-AIAF. They received electrical stimulation 15 minutes/day for three consecutive days and on the fourth day were tested in the elevated plus maze and the open field. The results of these study show that BIAF stimulation has a possible anxiolytic-like effect when compared to BIBF and AIBF (increase in the percentage of open-arms time, entries into the open-arms and total-distance-run in the open-arms). This is not due to any changes in locomotion (total-distance-run and open field exploration). It is concluded that frequency is more important than intensity for behavioral modification. This could explain some previous inconsistent results. The data also suggest that these parameters of stimulation have no anxiogenic effects. The role for dopaminergic and serotonergic systems must be subsequently evaluated as well as potential anxiogenic-like effects of low frequency stimulation.

Muscle Activity and Muscle Strength in Atypical Swallowing / Actividad Muscular y Fuerza Muscular en la Deglución Atípica

Abstract Objective: To characterize muscle activity and muscle strength in patients with atypical swallowing (AS; n = 88) and competent lips (CL) or incompetent lips (IL) versus a control group (Ctrl; n = 90) Methods and materials: An analytical case-control study was conducted using surface electromyography (sEMG) of the orbicularis oris, mentalis and masseter muscles. Compression forces of the orbicularis oris, right and left masseters muscle (Cfrmm, Cflmm)), tongue tensile strength (Tts) via myoscan analysis and resistance of the orbicularis oris (Roo) via dynamo-metry were determined. Comparisons were made with the Mann-Whitney U test under a 95% confidence interval. Results: The amplitude of the sEMG record of the orbicularis oris muscle, in maximal contraction, was lower (p<0.01) in the atypical swallowing group (596.40 ± 175.83) compared to controls (659.83 ± 203.79). The muscle strength studied in the experimental group was lower (p<0.01) than in controls (CFo: AS: 0.31 ± 0.13; Ctrl: 0.38 ± 0,11; Cfrmm: AS: 0.40 ± 0.08; Ctrl: 0.50 ± 0.11; Cflmm: AS: 0.41 ± 0.08; Ctrl: 0.58 ± 0.59; Tts, AS: 0.52 ± 0.14, Ctrl: 0.65 ± 0.14, and Roo: AS: 2.47 ± 0.61; Ctrl: 2.73 ± 0.60). Patients with incompetent lips had a greater muscle activity of the orbicularis oris in swallowing (AS of IL: 197.01 ± 85.84; AS of CL: 160.54 ± 97.03; Ctrl: 147.18 ± 80.10). Conclusion: Patients with atypical swallowing showed differences in the strength of studied muscles and the muscle activity of the orbicular oris muscle compared to controls.

Resumen Objetivo: Caracterizar la actividad y fuerza muscular de pacientes con deglución atípica (DA; N=88) con competencia labial (CL) o incompetencia labial (IL) vs un grupo control (Ctrl; N=90). Materiales y métodos: Estudio analítico de casos y controles se realizó una electromiografía de superficie (sEMG) de los músculos orbicular, mental y maseteros; se determinaron las fuerzas compresiva del orbicular de los labios (FCo), contráctil del masetero derecho (FCmd) e izquierdo (FCmi), extensora del músculo lingual (FEl) por mioescanografía y la fuerza de resistencia del orbicular de los labios (FRo) por dinamometría. Resultados: La amplitud del registro sEMG del músculo orbicular de los labios, en contracción máxima, fue menor (p<0.01) en el grupo DA(596,40±175,83) con respecto a los controles(659,83±203,79); la fuerza de los músculos estudiados en el grupo experimental fue menor (p<0,01) que en los controles (FCo: DA: 0,31±0,13; Ctrl: 0,38±0,11; FCmd: DA: 0,40±0,08; Ctrl: 0,50±0,11; FCmi: DA: 0,41±0,08; Ctrl: 0,58±0,59; FEl; DA: 0,52±0,14; Ctrl: 0,65±0,14; y FRo: DA: 2,47±0,61; Ctrl: 2,73±0,60). Los pacientes con DA-IL presentaron mayor actividad muscular del orbicular en deglución (DA-IL: 197,01±85,84; DA-CL: 160,54±97,03; Ctrl: 147,18±80,10). Conclusiones: Los pacientes con DA difieren en la fuerza de los músculos estudiados y en la actividad muscular del orbicular con respecto a los controles. Los pacientes con DA-CL y DA-IL difieren en la actividad y fuerza muscular del orbicular.

Different brain structures exhibit the same caffeine levels after the administration of a single dose of caffeine / Estructuras encefálicas distintas muestran concentración de cafeína similar después de la administración de una dosis única

Caffeine is a highly consumed stimulant of the nervous system. Although caffeine has diverse effects on different brain functions, little is known about the specific pharmacokinetics of this substance in the brain. For instance, most studies that assessed caffeine distribution in the rat brain have only measured caffeine levels in the cortex and striatum but not in more specific brain areas. Aims: The purpose of this work was to measure the caffeine concentration in blood and different brain regions (i.e. cortex, striatum, hippocampus, cerebellum and brainstem) at different times after the administration of a single intraperitoneal dose of caffeine. Methods: Adult Wistar rats (250 to 300 gr) were injected with a single intraperitoneal dose of 30 mg/Kg of caffeine. 20, 40, 60 and 80 minutes after administration, subjects were sacrificed by decapitation and samples of plasma, cerebral cortex, striatum, hippocampus, cerebellum and brainstem were obtained. Caffeine levels in the blood and each brain structure were measured by RP-HPLC and statistical analysis was performed. Results: Caffeine levels were higher in the plasma compared to all the brain structures studied. Different brain regions displayed similar caffeine concentrations. For all brain regions, the maximal concentration levels of caffeine were reached in the first 40 minutes after caffeine administration. Conclusions: The results support previous studies that show similar caffeine concentration between cortex and striatum, but also extend the results to other brain structures. Furthermore, caffeine concentration increases similarly in the plasma and brain structures. 40, 60 and 80 minutes after administration, caffeine concentration in the blood is almost two times higher than in the brain. This suggests that the effects of caffeine on different brain functions do not depend on pharmacokinetic differences between brain areas and are rather explained by pharmacodynamics.

Antecedentes: La cafeína es el estimulante del sistema nervioso más consumido a nivel mundial. Aunque, la cafeína tiene diferentes efectos sobre las funciones cerebrales, poco se sabe acerca de su farmacocinética en el cerebro. Por ejemplo, la mayoría de estudios que evaluaron la distribución de cafeína en el cerebro de rata han medido niveles de cafeína en corteza y estriado, pero no en áreas cerebrales más específicas. Objetivo: El propósito del trabajo fue medir la concentración de cafeína en sangre y diferentes regiones encefálicas (corteza, estriado, hipocampo, cerebelo, tallo cerebral), a diferentes tiempos, después de administrar una única dosis de cafeína. Método: Ratas Wistar adultas (250-300 gr) recibieron una dosis intraperitoneal de cafeína de 30mg/Kg de peso. 20, 40 60 y 80 minutos después de la administración, los sujetos se sacrificaron por decapitación y se obtuvieron muestras de plasma, corteza cerebral, estriado, hipocampo, cerebelo y tallo cerebral. Los niveles de cafeína en plasma y estructuras encefálicas se determinaron por RP-HPLC y se realizó análisis estadístico. Resultados: Los niveles de cafeína fueron mayores en plasma que en las regiones encefálicas estudiadas. Las distintas regiones encefálicas presentaron concentraciones similares de cafeína. En todas las regiones, la mayor concentración de cafeína se obtuvo 40 minutos después de la administración de cafeína. Conclusiones: Este estudio soporta resultados previos que muestran concentraciones similares de cafeína entre la corteza y el estriado, además los extiende a otras regiones encefálicas. La concentración de cafeína aumenta similarmente en plasma y estructuras encefálicas. 40, 60 y 80 minutos después de la administración, la concentración de cafeína en plasma es casi el doble de la encontrada en el cerebro. Lo anterior sugiere que los efectos de la cafeína en distintas funciones cerebrales no dependen de diferencias farmacocinéticas entre regiones encefálicas sino que son más bien explicadas por factores farmacodinámicos.

Efecto diferencial del subtipo clínico en los potenciales evocados cognitivos de pacientes con déficit de atención e hiperactividad / Differential effects of Attention deficit/hyperactivity disorder subtypes in event-related potentials

Introducción: Con el fin de mejorar el conocimiento de las bases neurofisiológicas del trastorno por déficit de atención e hiperactividad (TDAH) se realizó un estudio de potenciales evocados cognitivos en pacientes colombianos con TDAH combinado y TDAH inatento. Métodos: Estudio no experimental, de casos y controles y corte transversal, con una muestra conformada por 180 niños (n -132) y niñas (n-48), entre 5 y 15 (media, 9,25 ± 2,6) años de edad, pertenecientes a instituciones educativas de la ciudad de Manizales. Se dividió a los sujetos en un grupo con diagnóstico de TDAH y otro de control apareados por edad y sexo. Los sujetos fueron evaluados con los criterios del DSM-IV-TR, test de Conners, WISC-III y entrevista psiquiátrica estructurada MINIKID. Se realizó una revisión médica y se tomaron los potenciales evocados relacionados con eventos en modalidad visual y auditiva de atención pasiva (sin respuesta motora) dentro del paradigma oddball. Resultados: Los sujetos con TDAH presentaron diferencias en la amplitud N200 y latencia P300 en la modalidad auditiva y en la amplitud N200 en la modalidad visual. El subtipo clínico combinado mostró prolongación de la latencia de P300 en Fz, Cz y Pz en la tarea auditiva. El subtipo inatento mostró diferencias en la amplitud de la onda N200 y N100. Al comparar estos dos subtipos en la modalidad auditiva, el subtipo combinado tuvo mayor latencia de N100 y menor amplitud de P300 en Pz. Conclusiones: Los resultados indican una modulación diferencial de los componentes de los potenciales evocados cognitivos entre TDAH combinado y TDAH inatento.

Background: To better understand the neurophysiological substrates in attention deficit/hyperactivity disorder (ADHD), a study was performed on of event-related potentials (ERPs) in Colombian patients with inattentive and combined ADHD. Methods: A case-control, cross-sectional study was designed. The sample was composed of 180 subjects between 5 and 15 years of age (mean, 9.25 ± 2.6), from local schools in Manizales. The sample was divided equally in ADHD or control groups and the subjects were paired by age and gender. The diagnosis was made using the DSM-IV-TR criteria, the Conners and WISC-III test, a psychiatric interview (MINIKID), and a medical evaluation. ERPs were recorded in a visual and auditory passive oddball paradigm. Latency and amplitude of N100, N200 and P300 components for common and rare stimuli were used for statistical comparisons. Results: ADHD subjects show differences in the N200 amplitude and P300 latency in the auditory task. The N200 amplitude was reduced in response to visual stimuli. ADHD subjects with combined symptoms show a delayed P300 in response to auditory stimuli, whereas inattentive subjects exhibited differences in the amplitude of N100 and N200. Combined ADHD patients showed longer N100 latency and smaller N200-P300 amplitude compared to inattentive ADHD subjects. Conclusions: The results show differences in the event-related potentials between combined and inattentive ADHD subjects.

Lado de preferencia masticatoria en niños con fisura palatina: concordancia de tres métodos / Chewing side preference in children with cleft palate: concordance of three methods

Introducción: medir la concordancia de tres métodos para determinar el lado de preferencia masticatoria en niños con fisura palatina. Materiales y método: Se incluyeron 47 niños con paladar fisurado, similares en edad y estrato socioeconómico. Métodos: se usaron pruebas de Christensen y Radue (1985), el de Paphangkorakit y colaboradores (2006) y la Electromiografía de superficie (sEMG). Las comparaciones entre grupos se hicieron por métodos no paramétricos. Resultados: el método de Paphangkorakit y colaboradores (2006), no registró concordancia con la preferencia medida por el método de Christensen y Radue (1985) (χ2 de Pearson = 0,96, p = 0,619; Kappa = -0,08, p = 0,475). Los resultados muestran que el tipo de fisura no se asocia al lado de preferencia masticatoria medida por el método de Paphangkorakit y colaboradores, (2006) (χ2 de Pearson = 5,07; p = 0,281; Kappa = 0,07, p = 0,274), pero sí con el método de Christensen y Radue (1985) (χ2 de Pearson = 7,09; p = 0,029; asociación débil V de Cramer = 0,39; p = 0,029; Kappa = 0,19, p = 0,009). Los pacientes con fisura palatina derecha difieren de los pacientes con fisura bilateral, en la asimetría de amplitud sEMG en masticación (Derecha: 7,3 ± 12,8; Bilateral: -2,67 ± 6,61; U = 104; p = 0,038). Conclusión: no se encontró concordancia entre los dos métodos clínicos estudiados para la identificación de preferencia masticatoria, ni entre estos con la sEMG.

Introduction: the objective was to measure the concordance of three methods to determine chewing side preference in children with cleft palate. Materials and methods: The sample included 47 children with cleft palate and similar age and socioeconomic level. Methods: the test of Christensen & Radue (1985), the test of Paphangkorakit et al (2006) and surface electromyography (sEMG) were used. Comparisons among groups were made by non-parametric methods. Results: the method of Paphangkorakit et al (2006) did not show concordance with the preference measured by the Christensen & Radue method (1985) (Pearson’s χ2 = 0.96, p = 0,619; Kappa = ‒0.08, p = 0,475). The results showed that cleft type is not associated to chewing side preference measured by the method of Paphangkorakit et al (2006) (Pearson’s χ2 = 5.07; p = 0,281; Kappa = 0.07, p = 0,274) but by the method of Christensen & Radue (1985) (Pearson’s χ2 = 7.09; p = 0.029; weak Cramer’s V association = 0.39, p = 0.029; Kappa = 0.19, p = 0.009). Patients with right cleft palate differ from patients with bilateral cleft in terms of sEMG amplitude asymmetry while chewing (right: 7.3 ± 12.8; bilateral: ‒2.67 ± 6.61; U = 104; p = 0,038). Conclusion: no concordance was found between the two studied clinical methods to identify masticatory preference, nor between these and sEMG.