Gunther Fritzer

Morning headaches in patients with sleep disorders: a systematic polysomnographic study

OBJECTIVES Patients with sleep disorders suffer more often from headache after awakening than healthy subjects. However, it still is a matter of controversy whether this applies only to patients with sleep apnea syndrome (SAS) or also to patients with other diagnoses of sleep disorders. METHODS We asked all patients in our sleep laboratory about the frequency of past headaches and also ascertained the occurrence of morning headaches after awakening in the sleep laboratory. Polysomnographic recordings from nights before morning headache were compared with nights without following headache. Four hundred and thirty-two patients with sleep disorders (age range 18-86 years, 37% women) and 30 healthy subjects (age range 24-55 years, 27% women) participated in this prospective study. RESULTS The reported frequency of past headaches and the frequency of morning headache in the sleep laboratory were significantly increased in patients with SAS and other sleep disorders compared with healthy subjects. The occurrence of morning headache in the sleep laboratory was associated polysomnographically with a decrease in total sleep time, sleep efficiency and amount of rapid eye movement sleep and with an increase in the wake-time during the preceding night. CONCLUSIONS We conclude that morning headaches in patients with sleep disorders might be associated with particular disturbances of the preceding nights sleep. We speculate that dysregulation in anatomically identical central regions modulating sleep and nociception might be relevant to morning headache, rather than one particular sleep disorder such as SAS.

Early postnatal depletion of NMDA receptor development affects behaviour and NMDA receptor expression until later adulthood in rats—A possible model for schizophrenia

There is increasing evidence that a dysfunction of the N-methyl-d-aspartate (NMDA) receptor system plays a key role in the pathophysiology of schizophrenia. Non-competitive NMDA-antagonists induce schizophrenia-like symptoms and cognitive impairment in healthy humans as well as rodents. As receptor dysfunction precedes clinical disorder manifestation, the present study investigated whether transient perinatal NMDA antagonism constitutes a suitable long-term animal model for schizophrenia. Male Wistar rats were treated from postnatal days 6-21 with the NMDA receptor antagonist MK-801, and then subjected to behavioural analysis up to an age of 180d. Alterations in cortical NMDA receptor expression and lymphocyte cAMP-response-element-binding-protein (CREB) were assessed. In comparison to controls, MK-801-treated animals showed differences in behaviour up to an age of 180d. Western blot analysis revealed that transient perinatal application of MK-801 caused a persistent increase in cortical NMDA-R1 protein in combination with a persistent disturbance of CREB phosphorylation, a downstream target of NMDA signalling. This animal model demonstrates that early postnatal NMDA receptor blockade leads to schizophrenia-like symptoms with persistent behavioural and neurochemical disturbances throughout life. Therefore, it might provide a basis for further understanding of the disease and evaluation of new therapeutic strategies.

Sleep in major depression: relation to memory performance and outcome after interpersonal psychotherapy.

Background: Earlier findings suggest both a link between sleep and memory consolidation and a relationship between abnormal sleep at baseline and poor treatment outcome in major depression after interpersonal psychotherapy (IPT). Methods: Pre-treatment polysomnography was examined in 32 patients with a major depressive episode (mean age = 39.5 years, 20 women). Declarative memory was tested by the Rey-Osterrieth Complex Figure Test and a paired associative word list and procedural learning was assessed by a mirror tracing skill. All patients were treated with IPT according to the manual and did not receive any antidepressant medication. Twenty-three patients took part in a minimum of 12 sessions of IPT. Remission was defined as 2 consecutive weeks with a score <8 on the Hamilton Rating Scale of Depression. Results: Declarative visual memory performance was associated with total sleep time and total amount of rapid eye movement sleep. In IPT remitters (n = 14), there was a trend towards a decrease in rapid eye movement density (first period) and a significant decrease in delta power in pre-treatment sleep in comparison to non-remitters (n = 9). Treatment outcome after IPT was also associated with declarative memory performance at baseline (as a trend). Conclusions: Further indications of a role of sleep in memory processes and of the importance of specific sleep parameters as markers for a positive treatment response to psychotherapy were found.

Non-linear electroencephalogram dynamics in patients with spontaneous nocturnal migraine attacks

The present study was conducted to examine non-linear electroencephalogram (EEG) measures during the development of a spontaneous migraine attack. We investigated the sleep EEG of five patients with migraine without aura in the pain-free interval and at the onset of a nocturnal attack. Sleep EEG recordings were analysed using the method of global dimensional complexity compared to conventional sleep scoring techniques. We found no divergence between classical sleep architecture and the estimated dimensional course nor any relevant short-term changes related to the onset of headache. There was, however, a loss of dimensional complexity in the first two non-rapid eye movement sleep states in the migraine night, with statistical significance during the second sleep cycle. For the first time, these results provide evidence of a global dimension decrease that is related to cortical network changes during a migraine attack.

Modulation of involuntary and voluntary behavior following emotional stimuli in healthy subjects

INTRODUCTION Alterations of behavior control are core symptoms of various psychiatric disorders. Patients present with changes in complex behavior patterns and basic motor functions. Little is known about emotional modulation of voluntary behavior. Therefore, a paradigm was developed to study simultaneously influence of emotions on voluntary and involuntary movements. METHOD Healthy volunteers (n=30) documented aspects of their mood and personality including depression, anxiety, and impulsivity. Individuals were instructed to view color slides of different emotional content and switch off the slide after by pressing a button, which was placed in a standardized distance from the resting point. The startle reflex was elicited while looking at the slides and quantified by EMG. Kinematic measures of hand movements by infrared detection were used to analyze the patterns of voluntary movements. RESULTS This study confirmed previous findings about the modulation of the startle reflex by emotional stimuli which may reflect activity of the amygdala and subcortical stimulus processing. Voluntary movements, which may result from cortical processing of stimuli, were not influenced by the emotional context. In individuals with higher impulsivity scores, the startle reflex amplitudes were lower and relative time to peak velocity of the movement smaller. CONCLUSION Voluntary movements were not modulated by emotional stimuli, but time to peak velocity was shorter in individuals with greater impulsivity. The ability to generate adequate behavior as a key function of the brain is relevant for social functioning and activities of daily living. The studied paradigm could be useful to assess impulsivity and behavior control in psychiatric disorders.

Changes in cortical dynamics in the preictal stage of a migraine attack.

Neurophysiologic studies suggest that migraineurs without aura have a dysfunction of cortical information processing in the pain-free interval. In this study, the advanced method of nonlinear multielectrode sleep-EEG analysis is used to investigate changes of cortical activity in the preictal time span. Five patients (four women, one man; age range, 29 to 58 years) experiencing migraine without aura participated in the study. The patients spent two blocks in the sleep laboratory. The first block was taken in a headache-free interictal time interval, and the second block when the onset of a migraine attack was most likely. After a nocturnal migraine attack, the patient was asked to mark the maximum of migraine pain in a surface-head scheme. The comparison of preictal and interictal EEGs enabled the authors to obtain a topographical view of changes in cortical dynamics. In each patient map, an area was found that displayed a pronounced focus indicating the region of maximum change in dimensional complexity. It shows a clearly recognizable correspondence with the scalp topography of the later pain perception. These findings indicate an association between cortical status and pain lateralization in the preictal time span.