Changes in the rest-activity rhythm in migraine patients are associated with anxiety symptoms

Objective: To characterize rest-activity rhythm in chronic migraine (CM) and to investigate the relationship between this rhythm and depressive and anxiety symptoms in patients with CM. Methods: This was a study of adults aged 20 to 40 years. The rest-activity rhythm of patients with CM (n=23) and non-headache controls (NH, n=23) was assessed by actigraphy for 15 days, and they completed the following assessments: Visual Analogue Scale for pain intensity; Headache Diary; Headache Impact Test-6; Morningness-Eveningness Questionnaire; Pittsburgh Sleep Quality Index; Epworth Sleepiness Scale; Beck Depression Inventory; and State-Trait Anxiety Inventory. Results: Patients with CM showed less activity over 24 hours and more fragmented sleep. Reduced interdaily stability of the rest-activity rhythm was observed, with less robustness of this rhythm in the CM group. Multiple linear regressions revealed a significant association between the rest-activity rhythm and trait anxiety variables in patients with CM, specifically regarding the relative amplitude of the cycle, activity throughout 24 hours and during sleep, and robustness of the rest-activity rhythm. Conclusions: Our findings provide evidence that the robustness of the rest-activity rhythm, activity throughout 24 hours, and sleep fragmentation are associated with trait anxiety in patients with CM. Clinical trial registration: Brazilian Clinical Trials Registry (registration number: RBR-4M5J4S).

Changes in the rest-activity rhythm in migraine patients are associated with anxiety symptoms.

OBJECTIVE: To characterize rest-activity rhythm in chronic migraine (CM) and to investigate the relationship between this rhythm and depressive and anxiety symptoms in patients with CM. METHODS: This was a study of adults aged 20 to 40 years. The rest-activity rhythm of patients with CM (n=23) and non-headache controls (NH, n=23) was assessed by actigraphy for 15 days, and they completed the following assessments: Visual Analogue Scale for pain intensity; Headache Diary; Headache Impact Test-6; Morningness-Eveningness Questionnaire; Pittsburgh Sleep Quality Index; Epworth Sleepiness Scale; Beck Depression Inventory; and State-Trait Anxiety Inventory. RESULTS: Patients with CM showed less activity over 24 hours and more fragmented sleep. Reduced interdaily stability of the rest-activity rhythm was observed, with less robustness of this rhythm in the CM group. Multiple linear regressions revealed a significant association between the rest-activity rhythm and trait anxiety variables in patients with CM, specifically regarding the relative amplitude of the cycle, activity throughout 24 hours and during sleep, and robustness of the rest-activity rhythm. CONCLUSIONS: Our findings provide evidence that the robustness of the rest-activity rhythm, activity throughout 24 hours, and sleep fragmentation are associated with trait anxiety in patients with CM.

Nonparametric methods in actigraphy: An update.

Circadian rhythmicity in humans has been well studied using actigraphy, a method of measuring gross motor movement. As actigraphic technology continues to evolve, it is important for data analysis to keep pace with new variables and features. Our objective is to study the behavior of two variables, interdaily stability and intradaily variability, to describe rest activity rhythm. Simulated data and actigraphy data of humans, rats, and marmosets were used in this study. We modified the method of calculation for IV and IS by modifying the time intervals of analysis. For each variable, we calculated the average value (IVm and ISm) results for each time interval. Simulated data showed that (1) synchronization analysis depends on sample size, and (2) fragmentation is independent of the amplitude of the generated noise. We were able to obtain a significant difference in the fragmentation patterns of stroke patients using an IVm variable, while the variable IV60 was not identified. Rhythmic synchronization of activity and rest was significantly higher in young than adults with Parkinson׳s when using the ISM variable; however, this difference was not seen using IS60. We propose an updated format to calculate rhythmic fragmentation, including two additional optional variables. These alternative methods of nonparametric analysis aim to more precisely detect sleep-wake cycle fragmentation and synchronization.

Dream characteristics in a Brazilian sample: an online survey focusing on lucid dreaming.

During sleep, humans experience the offline images and sensations that we call dreams, which are typically emotional and lacking in rational judgment of their bizarreness. However, during lucid dreaming (LD), subjects know that they are dreaming, and may control oneiric content. Dreaming and LD features have been studied in North Americans, Europeans and Asians, but not among Brazilians, the largest population in Latin America. Here we investigated dreams and LD characteristics in a Brazilian sample (n = 3,427; median age = 25 years) through an online survey. The subjects reported recalling dreams at least once a week (76%), and that dreams typically depicted actions (93%), known people (92%), sounds/voices (78%), and colored images (76%). The oneiric content was associated with plans for the upcoming days (37%), memories of the previous day (13%), or unrelated to the dreamer (30%). Nightmares usually depicted anxiety/fear (65%), being stalked (48%), or other unpleasant sensations (47%). These data corroborate Freudian notion of day residue in dreams, and suggest that dreams and nightmares are simulations of life situations that are related to our psychobiological integrity. Regarding LD, we observed that 77% of the subjects experienced LD at least once in life (44% up to 10 episodes ever), and for 48% LD subjectively lasted less than 1 min. LD frequency correlated weakly with dream recall frequency (r = 0.20, p < 0.01), and LD control was rare (29%). LD occurrence was facilitated when subjects did not need to wake up early (38%), a situation that increases rapid eye movement sleep (REMS) duration, or when subjects were under stress (30%), which increases REMS transitions into waking. These results indicate that LD is relatively ubiquitous but rare, unstable, difficult to control, and facilitated by increases in REMS duration and transitions to wake state. Together with LD incidence in USA, Europe and Asia, our data from Latin America strengthen the notion that LD is a general phenomenon of the human species.

Neurobiology and clinical implications of lucid dreaming.

Several lines of evidence converge to the idea that rapid eye movement sleep (REMS) is a good model to foster our understanding of psychosis. Both REMS and psychosis course with internally generated perceptions and lack of rational judgment, which is attributed to a hyperlimbic activity along with hypofrontality. Interestingly, some individuals can become aware of dreaming during REMS, a particular experience known as lucid dreaming (LD), whose neurobiological basis is still controversial. Since the frontal lobe plays a role in self-consciousness, working memory and attention, here we hypothesize that LD is associated with increased frontal activity during REMS. A possible way to test this hypothesis is to check whether transcranial magnetic or electric stimulation of the frontal region during REMS triggers LD. We further suggest that psychosis and LD are opposite phenomena: LD as a physiological awakening while dreaming due to frontal activity, and psychosis as a pathological intrusion of dream features during wake state due to hypofrontality. We further suggest that LD research may have three main clinical implications. First, LD could be important to the study of consciousness, including its pathologies and other altered states. Second, LD could be used as a therapy for recurrent nightmares, a common symptom of depression and post-traumatic stress disorder. Finally, LD may allow for motor imagery during dreaming with possible improvement of physical rehabilitation. In all, we believe that LD research may clarify multiple aspects of brain functioning in its physiological, altered and pathological states.

Food entrainment: major and recent findings.

Mammals exhibit daily anticipatory activity to cycles of food availability. Studies on such food anticipatory activity (FAA) have been conducted mainly in nocturnal rodents. They have identified FAA as the behavioral output of a food entrained oscillator (FEO), separate of the known light entrained oscillator (LEO) located in the suprachiasmatic nucleus (SCN) of hypothalamus. Here we briefly review the main characteristics of FAA. Also, we present results on four topics of food anticipation: (1) possible input signals to FEO, (2) FEO substrate, (3) the importance of canonical clock genes for FAA, and (4) potential practical applications of scheduled feeding. This mini review is intended to introduce the subject of food entrainment to those unfamiliar with it but also present them with relevant new findings on the issue.

Daily anticipatory rhythms of behavior and body temperature in response to glucose availability in rats

When food is available recurrently at a particular time of day, several species increase their locomotion in the hours that precede food delivery, a phenomenon called food anticipatory activity (FAA). In mammals, many studies have shown that FAA is driven by a food-entrained circadian oscillator (FEO) that is distinct from the light-entrained pacemaker in the suprachiasmatic nucleus of the hypothalamus. Few studies have investigated the effect of sugar ingestion on food anticipatory rhythms and the FEO. We aimed to extend the understanding of the role of glucose on the emergence of food anticipatory rhythms by investigating whether glucose ingestion is sufficient to produce daily food anticipation, reflected by motor activity and core body temperature rhythms. Under a 12 h/12 h light/dark cycle, chow-deprived rats had glucose solution available between Zeitgeber Time (ZT) 6 and ZT 9 for 10 days (glucose restriction group), whereas control animals had chow available within the same time window (chow restriction group). Animals in both groups exhibited anticipatory motor activity and body temperature around the fourth day of the scheduled food restriction. Glucose-fed rats ingested ~15 kcal on the days immediately before FAA emergence and reached an intake of ~20 kcal/day, whereas chow-fed rats ingested ~40 kcal/day. The glucose restriction group exhibited a pattern of food anticipation (activity and temperature) that was extremely similar to that observed in the chow restriction group. We conclude that glucose ingestion is a sufficient temporal cue to produce recurrent food anticipation, reflected by activity and temperature rhythms, in rats.(AU)

Daily anticipatory rhythms of behavior and body temperature in response to glucose availability in rats

When food is available recurrently at a particular time of day, several species increase their locomotion in the hours that precede food delivery, a phenomenon called food anticipatory activity (FAA). In mammals, many studies have shown that FAA is driven by a food-entrained circadian oscillator (FEO) that is distinct from the light-entrained pacemaker in the suprachiasmatic nucleus of the hypothalamus. Few studies have investigated the effect of sugar ingestion on food anticipatory rhythms and the FEO. We aimed to extend the understanding of the role of glucose on the emergence of food anticipatory rhythms by investigating whether glucose ingestion is sufficient to produce daily food anticipation, reflected by motor activity and core body temperature rhythms. Under a 12 h/12 h light/dark cycle, chow-deprived rats had glucose solution available between Zeitgeber Time (ZT) 6 and ZT 9 for 10 days (glucose restriction group), whereas control animals had chow available within the same time window (chow restriction group). Animals in both groups exhibited anticipatory motor activity and body temperature around the fourth day of the scheduled food restriction. Glucose-fed rats ingested ~15 kcal on the days immediately before FAA emergence and reached an intake of ~20 kcal/day, whereas chow-fed rats ingested ~40 kcal/day. The glucose restriction group exhibited a pattern of food anticipation (activity and temperature) that was extremely similar to that observed in the chow restriction group. We conclude that glucose ingestion is a sufficient temporal cue to produce recurrent food anticipation, reflected by activity and temperature rhythms, in rats.

Influence of scheduled restricted feeding on reentrainment of motor activity rhythm after a 6-h light-dark advance in rats

Circadian rhythms are entrained to cyclic environmental cues such as the light-dark cycle and food availability. The suprachiasmatic nucleus of the hypothalamus is the main circadian oscillator in mammals and is entrained primarily by the light-dark cycle, although in some experimental situations food availability can affect its oscillation. Here we tested whether scheduled restricted feeding is capable of influencing the reentrainment of the motor activity rhythm (i.e., a behavioral rhythm controlled by the suprachiasmatic nucleus) to a 6-h phase advance of the light-dark cycle. Rats were housed in a standard 12 h:12 h light-dark cycle for 18 days, and then the time of lights-off was advanced. Rats subjected to scheduled restricted feeding starting on the first day of the light-dark shift showed faster reentrainment of the motor activity rhythm compared with control rats maintained with ad libitum food. The results showed that scheduled feeding effectively accelerates reentrainment of a behavioral circadian rhythm and suggest that the procedure may affect activity in the suprachiasmatic nucleus during the stage of reentrainment to light-dark shifts.

Influence of scheduled restricted feeding on reentrainment of motor activity rhythm after a 6-h light-dark advance in rats

Circadian rhythms are entrained to cyclic environmental cues such as the light-dark cycle and food availability. The suprachiasmatic nucleus of the hypothalamus is the main circadian oscillator in mammals and is entrained primarily by the light-dark cycle, although in some experimental situations food availability can affect its oscillation. Here we tested whether scheduled restricted feeding is capable of influencing the reentrainment of the motor activity rhythm (i.e., a behavioral rhythm controlled by the suprachiasmatic nucleus) to a 6-h phase advance of the light-dark cycle. Rats were housed in a standard 12 h:12 h light-dark cycle for 18 days, and then the time of lights-off was advanced. Rats subjected to scheduled restricted feeding starting on the first day of the light-dark shift showed faster reentrainment of the motor activity rhythm compared with control rats maintained with ad libitum food. The results showed that scheduled feeding effectively accelerates reentrainment of a behavioral circadian rhythm and suggest that the procedure may affect activity in the suprachiasmatic nucleus during the stage of reentrainment to light-dark shifts.(AU)

Activation of frontal neocortical areas by vocal production in marmosets.

Primates often rely on vocal communication to mediate social interactions. Although much is known about the acoustic structure of primate vocalizations and the social context in which they are usually uttered, our knowledge about the neocortical control of audio-vocal interactions in primates is still incipient, being mostly derived from lesion studies in squirrel monkeys and macaques. To map the neocortical areas related to vocal control in a New World primate species, the common marmoset, we employed a method previously used with success in other vertebrate species: Analysis of the expression of the immediate early gene Egr-1 in freely behaving animals. The neocortical distribution of Egr-1 immunoreactive cells in three marmosets that were exposed to the playback of conspecific vocalizations and vocalized spontaneously (H/V group) was compared to data from three other marmosets that also heard the playback but did not vocalize (H/n group). The anterior cingulate cortex, the dorsomedial prefrontal cortex and the ventrolateral prefrontal cortex presented a higher number of Egr-1 immunoreactive cells in the H/V group than in H/n animals. Our results provide direct evidence that the ventrolateral prefrontal cortex, the region that comprises Broca's area in humans and has been associated with auditory processing of species-specific vocalizations and orofacial control in macaques, is engaged during vocal output in marmosets. Altogether, our results support the notion that the network of neocortical areas related to vocal communication in marmosets is quite similar to that of Old world primates. The vocal production role played by these areas and their importance for the evolution of speech in primates are discussed.

[Brazilian guidelines for the treatment of narcolepsy]. / Diretrizes brasileiras para o tratamento da narcolepsia.

This manuscript contains the conclusion of the consensus meeting of the Brazilian Sleep Association with Brazilian sleep specialists on the treatment of narcolepsy based on the review of medical literature from 1980 to 2010. The manuscript objectives were to reinforce the use of agents evaluated in randomized placebo-controlled trials and to issue consensus opinions on the use of other available medications as well as to inform about safety and adverse effects of these medications. Management of narcolepsy relies on several classes of drugs, namely, stimulants for excessive sleepiness, antidepressants for cataplexy and hypnotics for disturbed nocturnal sleep. Behavioral measures are likewise valuable and universally recommended. All therapeutic trials were analyzed according to their class of evidence. Recommendations concerning the treatment of each single symptom of narcolepsy as well as general recommendations were made. Modafinil is the first-line pharmacological treatment of excessive sleepiness. Second-line choices for the treatment of excessive sleepiness are slow-release metylphenidate followed by mazindol. The first-line treatments of cataplexy are the antidepressants, reboxetine, clomipramine, venlafaxine, desvenlafaxine or high doses of selective serotonin reuptake inibitors antidepressants. As for disturbed nocturnal sleep the best option is still hypnotics. Antidepressants and hypnotics are used to treat hypnagogic hallucinations and sleep paralysis.

Diretrizes brasileiras para o diagnóstico de narcolepsia / Brazilian guidelines for the diagnosis of narcolepsy

Este artigo relata as conclusões da reunião de consenso com médicos especialistas sobre diagnóstico de narcolepsia baseada na revisão dos artigos sobre narcolepsia listados no Medline entre 1980 e 2010. A narcolepsia é uma doença crônica de início entre a primeira e segunda décadas de vida do indivíduo. Os sintomas essenciais são cataplexia e sonolência excessiva. A cataplexia é definida como episódios súbitos, recorrentes e reversíveis de fraqueza da musculatura esquelética desencadeados por situações de conteúdo emocional. Os sintomas acessórios são alucinações hipnagógicas, paralisia do sono e sono fragmentado. Critérios de diagnóstico clínico de acordo com a Classificação Internacional dos Transtornos do Sono são de sonolência excessiva e cataplexia. Recomenda-se a realização de polissonografia seguida do teste de latência múltipla do sono em um laboratório de sono para confirmação e diagnóstico de comorbidades. Quando não houver cataplexia, deve haver duas ou mais sonecas com sono REM no teste de latência múltipla do sono. Tipagem HLA-DQB1*0602 positiva com níveis de hipocretina-1 abaixo de 110pg/mL devem estar presentes para o diagnóstico de narcolepsia sem cataplexia e sem sonecas com sono REM.

This manuscript contains the conclusion of the consensus meeting on the diagnosis of narcolepsy based on the review of Medline publications between 1980-2010. Narcolepsy is a chronic disorder with age at onset between the first and second decade of life. Essential narcolepsy symptoms are cataplexy and excessive sleepiness. Cataplexy is defined as sudden, recurrent and reversible attacks of muscle weakness triggered by emotions. Accessory narcolepsy symptoms are hypnagogic hallucinations, sleep paralysis and nocturnal fragmented sleep. The clinical diagnosis according to the International Classification of Sleep Disorders is the presence of excessive sleepiness and cataplexy. A full in-lab polysomnography followed by a multiple sleep latency test is recommended for the confirmation of the diagnosis and co-morbidities. The presence of two sleep-onset REM period naps in the multiple sleep latency test is diagnostic for cataplexy-free narcolepsy. A positive HLA-DQB1*0602 with lower than 110pg/mL level of hypocretin-1 in the cerebrospinal fluid is required for the final diagnosis of cataplexy- and sleep-onset REM period -free narcolepsy.

Diretrizes brasileiras para o tratamento da narcolepsia / Brazilian guidelines for the treatment of narcolepsy

Este artigo relata as conclusões da reunião de consenso da Associação Brasileira de Sono com médicos especialistas brasileiros sobre o tratamento da narcolepsia, baseado na revisão dos artigos sobre narcolepsia publicados entre 1980 e 2010. Os objetivos do consenso são valorizar o uso de agentes avaliados em estudos randomizados placebo-controlados, emitir recomendações de consenso para o uso de outras medicações e informar pontos importantes a respeito da segurança e efeitos adversos das medicações. O tratamento da narcolepsia é baseado em diversas classes de agentes, estimulantes para sonolência excessiva, agentes antidepressivos para cataplexia e hipnóticos para sono noturno fragmentado. Medidas comportamentais são igualmente importantes e recomendadas universalmente. Todos os ensaios clínicos terapêuticos foram classificados de acordo com o nível de qualidade da evidência. Recomendações terapêuticas individualizadas para cada tipo de sintoma e recomendações gerais foram formuladas pelos autores. Modafinila é indicada como a primeira escolha para o tratamento da sonolência diurna. Agentes de segunda escolha para o tratamento da sonolência excessiva são metilfenidato de liberação lenta seguido pelo mazindol. Reboxetina, clomipramina, venlafaxina, desvenlafaxina e os inibidores seletivos de recaptação de serotonina em doses altas são a primeira escolha para o tratamento da cataplexia. Hipnóticos são utilizados para o tratamento do sono noturno fragmentado. Antidepressivos e hipnóticos são igualmente utilizados para o tratamento das alucinações hipnagógicas e paralisia do sono.

This manuscript contains the conclusion of the consensus meeting of the Brazilian Sleep Association with Brazilian sleep specialists on the treatment of narcolepsy based on the review of medical literature from 1980 to 2010. The manuscript objectives were to reinforce the use of agents evaluated in randomized placebo-controlled trials and to issue consensus opinions on the use of other available medications as well as to inform about safety and adverse effects of these medications. Management of narcolepsy relies on several classes of drugs, namely, stimulants for excessive sleepiness, antidepressants for cataplexy and hypnotics for disturbed nocturnal sleep. Behavioral measures are likewise valuable and universally recommended. All therapeutic trials were analyzed according to their class of evidence. Recommendations concerning the treatment of each single symptom of narcolepsy as well as general recommendations were made. Modafinil is the first-line pharmacological treatment of excessive sleepiness. Second-line choices for the treatment of excessive sleepiness are slow-release metylphenidate followed by mazindol. The first-line treatments of cataplexy are the antidepressants, reboxetine, clomipramine, venlafaxine, desvenlafaxine or high doses of selective serotonin reuptake inibitors antidepressants. As for disturbed nocturnal sleep the best option is still hypnotics. Antidepressants and hypnotics are used to treat hypnagogic hallucinations and sleep paralysis.

[Brazilian guidelines for the diagnosis of narcolepsy]. / Diretrizes brasileiras para o diagnóstico da narcolepsia.

This manuscript contains the conclusion of the consensus meeting on the diagnosis of narcolepsy based on the review of Medline publications between 1980-2010. Narcolepsy is a chronic disorder with age at onset between the first and second decade of life. Essential narcolepsy symptoms are cataplexy and excessive sleepiness. Cataplexy is defined as sudden, recurrent and reversible attacks of muscle weakness triggered by emotions. Accessory narcolepsy symptoms are hypnagogic hallucinations, sleep paralysis and nocturnal fragmented sleep. The clinical diagnosis according to the International Classification of Sleep Disorders is the presence of excessive sleepiness and cataplexy. A full in-lab polysomnography followed by a multiple sleep latency test is recommended for the confirmation of the diagnosis and co-morbidities. The presence of two sleep-onset REM period naps in the multiple sleep latency test is diagnostic for cataplexy-free narcolepsy. A positive HLA-DQB1*0602 with lower than 110pg/mL level of hypocretin-1 in the cerebrospinal fluid is required for the final diagnosis of cataplexy- and sleep-onset REM period -free narcolepsy.

Light-dark cycle synchronization of circadian rhythm in blind primates.

BACKGROUND: Recently, several papers have shown that a small subset of retinal ganglion cells (RGCs), which project to the suprachiasmatic nucleus (SCN) and contain a new photopigment called melanopsin, are the photoreceptors involved in light-dark entrainment in rodents. In our primate colony, we found a couple of common marmosets (Callithrix jacchus) that had developed progressive and spontaneous visual deficiency, most likely because of retinal degeneration of cones and/or rods. In this study, we evaluated the photoresponsiveness of the circadian system of these blind marmosets. METHODS: Two blind and two normal marmosets were kept in cages with a controlled light-dark cycle (LD) to study photoentrainment, masking, and phase response to a dark pulse. RESULTS: Blind marmosets were entrained with the new LD cycle when light onsets were delayed and advanced by 6 hours. In constant light conditions, blind marmosets free-ran with a period of 23.2 hours, while normal animals free-ran with a period of 23.6 hours. All marmosets responded to dark pulses in the early subjective day with phase delays and with phase advances in the late subjective day. CONCLUSION: Our results demonstrate that light can synchronize circadian rhythms of blind marmosets and consequently, that this species could be a good primate model for circadian photoreception studies.

Epidemiologia da doença de Chagas na zona rural do município de Teresina-Piauí, Brasil / The epidemiology of Chagas' disease in rural area of the city of Teresina-Piauí, Brazil

Na área rural do nunicípio de Teresina-Piauí, foram capturados 129 triatomíneos distribuídos em (a) ecótopos artificiais: habitaçöes (1 Triatoma brasilensis, 1 Panstrongylus geniculatus, 1 Rhodnius pictipes e 1 Rhodnius prolixus) e galpäo abandonado (7 Rhodnius nasutus) e (b) ecótopos naturais: Orbignya martiana (41 Rhodnius neglectus, 33 Rhodnius prolixus e 41 Rhodnius nasutus) e Copernicia cerifera (3 Rhodnius neglectus). Cerca de 22,6 por cento dos triatomíneos capturados estavam infectados por flagelados, sendo 30 por cento no ambiente artificial e 21,9 por cento no ambiente natural. Dos 28 mamíferos capturados e examinados, 7 Didelphis albiventris, 2 Rattus rattus e I Tamandua tetradactyla apresentavam-se positivos para flagelados. Os flagelados encontrados nos triatomíneos e nos mamíferos eram semelhantes ao Trypanosoma cruzi. Das 123 reaçöes sorológicas, por imunofluorescência indireta, realizadas na populaçäo, duas (1,6 por cento) foram reativas