EEG source activity during processing of neutral stimuli in subjects with anxiety disorders.

Anxiety disorders are a social problem due to their prevalence and consequences. It is crucial to explore the influence of anxiety on cognitive processes. In this study we recorded EEG activity from 73 subjects (35 patients, 38 controls, matched for age and education) during performance of the Continuous Attention Task. We used low resolution electromagnetic tomography (LORETA) for evaluation of mechanisms of impaired cognitive performance in anxiety disorders. Analysis showed that patients with anxiety disorders committed more errors than the controls, had a short latency of P300 and higher amplitude of ERPs at all steps of stimulus processing. Furthermore, we showed that there was a relationship between the scores of Hamilton Anxiety Scale and Beck Depression Inventory, and amplitudes and latencies of ERPs. The results of LORETA analysis showed that enhanced neural responses were found within circuits mediating visual information processing, sustained attention and anxiety. Also, we found higher current density within areas playing an important role in the brain fear network - anterior cingulate and anterior part of insula. Electrophysiological neuroimaging showed greater recruitment of cognitive resources in anxiety disorders, evidenced by higher current density and activation of greater number of brain areas. Despite the strategy employed to compensate for cognitive problems, the anxiety patients did not achieve the same performance as controls. Present study demonstrates that anxiety disorders influence processing of neutral stimuli and this influence is observable at both behavioral and electrophysiological level. The data suggests instability of neural systems responsible for information selection, working memory, engagement and focusing of attention.

Sleepwalking episodes are preceded by arousal-related activation in the cingulate motor area: EEG current density imaging.

OBJECTIVE: To investigate local arousal fluctuations in adults who received ICSD-2 diagnosis of somnambulism. METHODS: EEG neuroimaging (eLORETA) was utilized to compare current density distribution for 4s epochs immediately preceding sleepwalking episode (from -4.0 s to 0 s) to the distribution during earlier 4s epochs (from -8.0 s to -4.0 s) in 20 EEG segments from 15 patients. RESULTS: Comparisons between eLORETA images revealed significant (t>4.52; p<0.05) brain activations before onset of sleepwalking, with greater current density within beta 3 frequency range (24-30 Hz) in Brodmann areas 33 and 24. CONCLUSIONS: Sleepwalking motor events are associated with arousal-related activation of cingulate motor area. SIGNIFICANCE: These results support the notion of blurred boundaries between wakefulness and NREM sleep in sleepwalking.

[Cognitive behavioral therapy for chronic insomnia]. / Terapia poznawczo-behawioralna w leczeniu bezsennosci przewleklej.

AIM: To evaluate the efficacy of cognitive behavioral therapy (CBT-I) in chronic insomnia treatment. METHOD: 236 patients with ICD- 10 nonorganic insomnia were assigned to group CBT-I (6 sessions, 6-10 patients). From this pool, 72 participants with no history of other psychiatric or sleep disorders conditions were selected. Eventually, 51 patients (40 female, mean age: 54.6+/-13.9y, mean insomnia duration: 7+/-6.3y) and 51 matched healthy controls (mean age: 55.4+/-14.3y) completed the study. Outcomes in the insomnia group at baseline and post-treatment were compared to control group. Subjects underwent sleep diary, the Athens Insomnia Scale (AIS), the Beck Depression Inventory (BDI), the Ford Insomnia Response to Stress Test (FIRST), the SF-36 questionnaire and the State-Trait Anxiety Inventory (STAI). RESULTS: At baseline, groups differed significantly in most dependent variables. At posttreatment, a substantial improvement in all sleep parameters was observed in insomnia group: sleep latency, number ofawakenings, wake time after sleep onset, sleep time, sleep efficiency, sleep quality and frequency of hypnotic use. These outcomes were accompanied by lower AIS and FIRST scores, reductions of depression and anxiety symptoms, and improved energy and social functioning ratings. All changes were maintained during the 3-month follow-up. Only 10/51 patients had no clinically meaningful improvement at any post-treatment time points. After the therapy, patients did not differ significantly from good sleepers in number of awakenings, sleep quality, feeling in the morning, depression and anxiety symptoms, and quality of life related to mental health. CONCLUSIONS: The CBT-I produced a sustained, clinically meaningful improvement in nocturnal sleep and daytime functioning.

Age-dependent symptomatology of depression in hospitalized patients and its implications for DSM-5.

BACKGROUND: We investigated effects of current age and age at onset on symptomatology of depression with reference to proposed revisions in DSM-5. METHODS: The study entailed medical records of 326 inpatients diagnosed with major depressive disorder, including 520 depressive episodes, with 113 first episodes lifetime. Subjects were divided into three groups: young-adults, middle-aged adults and older adults. RESULTS: In young-adults, active suicidal ideation, lifetime suicidal attempts, irritability, anhedonia and persistent depressive symptoms between the episodes were more frequent than in the other groups. Among older adults, depression was associated with insomnia, hypochondriasis, somatization, decreased appetite, weight loss, memory impairment and decreased activity. The older age was not associated with higher number of previous episodes of depression, bigger severity or duration of a single episode or a different degree of remission. Early-onset depression was associated with more suicidal attempts. LIMITATIONS: The study was retrospective and the sample may be treated only as representative for hospitalized depressed patients. CONCLUSIONS: Age and age at onset are important factors influencing the course and symptomatology of a depressive episode. Depressive episodes with anxiety and with suicide risk severity are important specifiers that vary with the age at onset and/or age of the patient and should be considered for inclusion in the DSM-5 revision.

Cognitive functions in abstinent alcohol-dependent patients.

The objective of this cross-sectional study was to compare cognitive functioning of abstaining alcohol-dependent (AD) male patients and healthy controls as well as to investigate whether their cognitive performance varied by abstinence length. Forty-two maintaining abstinent (AD) patients and 34 healthy controls were examined. Tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) were used to assess cognitive functions. Differences in cognitive performance were found between AD patients and healthy controls. Nonverbal tasks in cognitive domains such as attention, visual memory and working memory were impaired in AD patients who presented deficits in visual episodic memory, had slower reaction time and reduced working memory span. Patients who were abstinent for less than one year made more errors in both attentional set shifting and working memory tests than healthy controls and patients with longer durations of abstinence. Impairments identified in multiple cognitive domains in abstinent alcohol-dependent subjects suggest functional deficits in extensive brain networks connecting interrelated brain structures. Attentional control and spatial working memory were less impaired in those AD patients who maintained abstinence for at least one year.

Serum cortisol concentration in patients with major depression after treatment with fluoxetine.

Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis and elevated cortisol levels is characteristic of the pathophysiology of major depressive disorder (MDD). The aim of this study was to determine whether increased plasma cortisol levels appear in patients with major depression and if effective antidepressant treatment by fluoxetine leads to regulation of cortisol level. This aim was realized by describing and validation of methods of determining fluoxetine and cortisol in serum and searching for correlation between their concentrations in patients with endogenous depression, the therapeutic effect as assessed in Hamilton Depression Rating Scale (HDRS), age and sex of patients. Plasma cortisol and fluoxetine levels were measured using high performance liquid chromatography (HPLC) methods with applying Shimadzu chromatograph with UV detection. Plasma cortisol and fluoxetine levels were measured at time zero (before therapy) and after 6h, 24h, 2, 4, 6 and 8 weeks of fluoxetine administration in patients with major depression qualified for therapeutic drug monitoring (TDM). The study included 21 patients (14 women, 7 men; mean age 29-75 years) and 24 healthy comparison subjects. The patients had a mean score on the 21-item HDRS. As the effect of fluoxetine administration the decrease of the level of cortisol was observed in patients who responded to the therapy (the reduction of points in HDRS scale in at least 50%). The validation parameters of HPLC method of fluoxetine and cortisol determination indicate the possibility of applying them for determination of both: the level of concentration of the drug in therapeutic drug monitoring and the level of cortisol in serum of patients with endogenous depression.

Waking EEG in primary insomnia.

Quantitative analysis of the waking EEG has been proposed as an objective method for measuring neurobehavioral impairment in primary insomnia. Thirty six patients with DSM-IV primary insomnia diagnosis (mean age 36 years) and 29 controls, matched for age and education, participated in the study. Waking EEG from 21 scalp electrodes was subjected to spectral analyses using a fast Fourier transform algorithm. Significantly lower values of power in the theta range and higher values of beta power were found in insomniacs as compared to control subjects. This theta power decrease in patients suffering from insomnia was not uniform throughout the brain, but it was pronounced in prefrontal derivations. Lower values of theta power correlated negatively and higher values of beta power correlated postively with Hyperarousal Scale score. Results of the research presented here support the notion of twenty-four hour hyperarousal in primary insomnia. Attenuated theta and enhanced beta power can be electrophysiological correlates of dysfunctional arousal in insomnia. Less waking theta power in insomniacs suggests a decrease in homeostatic sleep propensity.

[Validation of the Polish version of the Athens Insomnia Scale]. / Walidacja Atenskiej Skali Bezsennosci.

AIMS: To validate the Polish version of the Athens Insomnia Scale (AIS), the instrument designed for quantitative measurement of the severity of insomnia based on the ICD-10 criteria. METHOD: The AIS was administered to 356 subjects: 160 patients from the sleep clinic presenting with ICD-10 non-organic insomnia (90f; mean age: 44.9 +/- 15.7y) and 196 self-defined good sleepers (106f; mean age: 43.9 +/- 13.4y). To assess psychometric properties of the scale, principal component analysis, Cronbach's alpha, Pearson's correlation (test-retest reliability: two weeks interval; n = 48) and sensitivity-specificity analysis were computed. RESULTS: Using the factor analysis only one factor was extracted, which accounted for 60.2% of the variance. The internal consistency (Cronbach's alpha = 0.90) and the test-retest reliability (r2 = 0.92) of the AIS were found to be very satisfactory. These values remain practically unchanged when any of the items was removed from the analysis. As expected, subjects with insomnia scored significantly higher on the AIS than good sleepers (14.2 +/- 3.9 pts vs. 4.8 +/- 3 pts; t = 24.9; p < 0.001). Considering the balance between sensitivity and specificity, a score of 8 was indicated as the optimum cut-off, with 89% overall correct case identification--94% patients with insomnia and 84% healthy controls. CONCLUSIONS: Standardisation of the diagnostic process of insomnia is a highly important task in clinical practice, epidemiological considerations and treatment outcomes assessment. The AIS is a brief, self-reported measure of insomnia that may improve these assessments. The good psychometric properties of the Polish version of the AIS were confirmed in the present study.

Serum cortisol concentration in patients with major depression after treatment with clomipramine.

Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis and elevated cortisol (CORT) levels are characteristics of the pathophysiology of major depressive disorder. The aim of this study was to determine whether increased plasma CORT levels appear in patients with major depression and if effective antidepressant treatment by clomipramine (CLO) leads to regulation of CORT level. Plasma CORT levels were measured using high performance liquid chromatography (HPLC) methods in patients with major depression at time zero (before therapy) and after 3 h, 24 h, 4, 6 and 8 weeks of CLO administration. The study included 17 patients (12 women, 5 men; mean age 54.5 years, SD =12.3) and 21 healthy comparison subjects. The patients had a mean score on the 21-item Hamilton Depression Rating Scale (HDRS) of 26.8 (range 22-35). Eight of the patients with major depression recruited for the study showed a 46% increase in CORT concentration compared to the established standard. In 13 patients treated with CLO, serum CLO levels reached a therapeutic range. In recovered depressed patients, antidepressant treatment significantly reduced HDRS scores from the 6th week of treatment. A drop in plasma CORT levels in recovered depressed subjects occurred 0 to 6 weeks after CLO treatment (n = 5, p < 0.046). However, neither subject group exhibited any definitive markers of CORT secretion. In the population studied, patients had distinct profiles of HPA axis dysregulation. Finding a linear correlation between lower CORT secretion and therapeutic plasma CLO levels is the first aim of monitored therapy and may be important for understanding the pathophysiology of major depressive disorder.

On the nature of heart rate variability in a breathing normal subject: a stochastic process analysis.

Human heart rate is moderated by the autonomous nervous system acting predominantly through the sinus node (the main cardiac physiological pacemaker). One of the dominant factors that determine the heart rate in physiological conditions is its coupling with the respiratory rhythm. Using the language of stochastic processes, we analyzed both rhythms simultaneously taking the data from polysomnographic recordings of two healthy individuals. Each rhythm was treated as a sum of a deterministic drift term and a diffusion term (Kramers-Moyal expansion). We found that normal heart rate variability may be considered as the result of a bidirectional coupling of two nonlinear oscillators: the heart itself and the respiratory system. On average, the diffusion (noise) component measured is comparable in magnitude to the oscillatory (deterministic) term for both signals investigated. The application of the Kramers-Moyal expansion may be useful for medical diagnostics providing information on the relation between respiration and heart rate variability. This interaction is mediated by the autonomous nervous system, including the baroreflex, and results in a commonly observed phenomenon--respiratory sinus arrhythmia which is typical for normal subjects and often impaired by pathology.

Cortisol level in men with major depressive disorder treated with fluoxetine or imipramine.

The aim of this research was to find out whether increased plasma cortisol levels appear in unipolar or bipolar patients with major depressive disorder (MDD) and whether the effective antidepressant treatment by imipramine and fluoxetine leads to regulation of the cortisol level. Cortisol levels were studied in two groups of patients with major depressive disorder: unipolar and bipolar patients treated with fluoxetine (doses: 20-60 mg/day). This group included 5 patients (age 29-46 yr); unipolar and bipolar subjects treated with imipramine (50-150 mg/day), this group included 5 patients (aged 24-70 yr). Cortisol and fluoxetine or imipramine plasma levels were assessed using HPLC methods: before treatment, after 3, 6 and 24 h of drug administration as well as in the 2nd, 4th, 6th, and 8th week of antidepressant treatment. HPLC methods were previously validated. The research conducted and the clinical data may be useful for proving the essential role of enhanced HPA axis activity for the pathogenesis and depressive disorder proceedings.

Explicit parameterization of sleep EEG transients.

Adaptive time-frequency approximations, implemented via the matching pursuit algorithm, offer description of local signals structures in terms of their time occurrence and width, frequency and amplitude. This allows to construct explicit filters for finding EEG waveforms, known from the visual analysis, in the matching pursuit decomposition of signals. In such a way detectors of relevant structures of both transient and oscillatory nature can be constructed in the space of physically meaningful parameters. This study presents evaluation of changes of power and frequency of sleep spindles and delta waves, related to the depth of the sleep, which were previously assessed in a qualitative way. We confirm quantitatively the decrease of frequencies of sleep spindles and delta waves with the depth of the sleep.

Characterization of insomnia in patients with essential hypertension.

INTRODUCTION: Insomnia may increase risk of cardiovascular events. There is little data available reporting the prevalence and clinical relevance of insomnia in patients with essential hypertension. Therefore, the aim of the study was to investigate the relationship between insomnia and different clinical and biochemical parameters in essential hypertension patients. METHODS: Four hundred and thirty-two patients (mean age 47+/-13 years; 253 male, 179 female) with essential hypertension were screened for insomnia using the athens Insomnia Scale (AIS). Several variables including age, sex, known duration of hypertension, body mass index, creatinine, left ventricular mass index, coexisting disorders, smoking status and alcohol use were analysed. Twenty-four-hour ambulatory blood pressure measurements (ABPM) were performed. RESULTS: Among patients included in the study, 207 subjects (mean age: 49+/-13 years; 47.9%) had an AIS score of 15 or higher and were identified as insomniacs. Insomnia was more frequent in women than in men (60.9% vs 38.7%, p<0.001) and was reported more frequently in patients with coronary artery disease. Subjects with insomnia were older and had longer duration of hypertension. There were no differences between insomniacs and non-insomniacs in ABPM parameters. A relationship was found between the number of antihypertensive drugs and insomnia frequency. There were correlation between AIS score and age (r=0.21; p<0.001) and duration of hypertension (r=0.22; p<0.001). In the sub-group of untreated essential hypertension patients, there were negative correlations between AIS score and night fall in systolic and diastolic blood pressure. CONCLUSION: Our results showed that insomnia is common in patients with essential hypertension and indicate an association between insomnia and gender, known duration of hypertension and number of hypertensive drugs taken. Untreated essential hypertension insomniacs were characterized by less pronounced nocturnal fall in both systolic and diastolic blood pressure compared with non-insomniacs.

Therapeutic tricyclic antidepressant drug monitoring in younger and older depressive patients.

The present study shows the evaluation of clinical state and serum level of tricyclic antidepressants in thirty-eight depressive younger and elderly patients during 8-week observation. We observed no statistically significant differences, neither in psychometric scale scores nor in drug serum levels in both groups of patients.

Sleepwalking and night terrors: psychopathological and psychophysiological correlates.

Sleepwalking and night terrors are considered to be manifestations of the same nosologic continuum. It has been proposed that a sudden arousal from non-rapid eye movement (NREM) sleep is the cause of these disorders. Benign forms of NREM arousal parasomnias occur frequently in childhood and attenuate in teen years; however, they can persist into or begin in adulthood. The available literature documents high levels of psychopathology in adult patients. Sleepwalking and night terrors are most likely to manifest during the first episode of slow wave sleep, but may also appear any time during NREM sleep. The hypersynchronous delta activity, previously considered to be a hallmark of somnambulism, has proven to be unspecific. Post-arousal EEG activity reveals altered consciousness during sleepwalking and sleep terror episodes. Pathophysiology of NREM arousal parasomnias consists of predisposing factors, which may be a genetically determined tendency for deep sleep, facilitating factors which deepen sleep and increase slow wave sleep, and triggering factors which increase sleep fragmentation, such as stress, environmental or endogenous stimuli, and stimulants. Recently published data on low delta power in the first sleep cycle and slow decline of delta power in successive sleep cycles suggest a chronic inability to sustain slow wave sleep.

High resolution parametric description of slow wave sleep.

We propose a new framework for quantitative analysis of sleep EEG, compatible with the traditional analysis, based upon adaptive time-frequency approximation of signals. Using a high resolution description of EEG rhythms and transients in terms of their time occurrence and width, frequency and amplitude, we present a detailed detection and parameterization of delta waves, including also the time occupied by each delta wave-a parameter inaccessible directly by previously applied signal processing methods. To validate the proposed parameterization, we construct a simple detector of sleep stages 3 and 4, based explicitly upon the classical criteria related to delta waves. To properly compare its performance to the inter-expert agreements and other expert systems, we sort out and discuss the methodology of reporting concordance in this context. Since the proposed parameterization proves to be compatible with the visual analysis of EEG, we can derive new variables for quantitative analysis of EEG patterns recognized for decades. As examples, we present a continuous description of delta waves and sleep spindles in the overnight sleep, and compare results to the traditional FFT-based estimates.

Increased prefrontal event-related current density after sleep deprivation.

To investigate how partial sleep loss affects temporal and spatial pattern of information flow, we analyzed sources of brain electrical activity during continuous attention test. Sixteen physicians recruited from the university hospitals participated in the study. Each participant served as his own control. All participants underwent two test sessions including the Stanford Sleepiness Scale (SSS), the Beck Depression Inventory (BDI), the Selective Reminding Test (SRT), and the Continuous Attention Test (CAT). The CAT items were used as stimuli in event-related potential (ERP) recordings. EEG was recorded from 21 electrodes, according to the international 10-20 system. The sources of bioelectrical activity were computed with low resolution electromagnetic tomography (LORETA). Estimated sleep time was significantly shorter on nights spent on duty than on nights of normal sleep at home. Sleep loss resulted in significant increase in SSS and BDI scoring, and impairment of immediate recall. Performance on the CAT remained relatively intact. Under the sleep loss condition compared to baseline, significant differences in brain activity occurred only for targets. Within the P1 time frame, sleep loss led to greater activation in the right Brodmann's area 9/10. For the N1 component, significant differences were localized on the lateral surface of the right frontal lobe, in Brodmann's areas 8 and 9. No significant effects of sleep deprivation on the P3 component were found. Our results are consistent with earlier data indicating that increased activation of the prefrontal cortex allows the maintainance of performance during periods of sleep loss.