Visual-spatial and visuomotor functioning in adults with neurofibromatosis type 1.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a neurodevelopmental genetic disorder associated with visual-spatial and visuomotor deficits, which have not been studied well in adults with NF1. METHODS: In 22 adults with NF1 and 31 controls, visuomotor functioning was assessed by measuring eye latency, hand latency and hand accuracy during visuomotor tasks. Visual-spatial functioning was assessed by measuring eye movement responses during the Visual Threshold Task. RESULTS: The NF1 group had a significantly shorter eye latency than the control group and was less accurate in their hand movements during specific visuomotor tasks. The groups showed no differences in eye movement responses during the Visual Threshold Task and in hand latency during the visuomotor tasks. CONCLUSIONS: In contrast to studies in children with NF1, we found no alterations in visual-spatial information processing in adults. Impairments in eye latency and hand accuracy during specific visuomotor tasks may indicate deficits in visuomotor functioning in adults with NF1.

Plasticity of visual evoked potentials in patients with neurofibromatosis type 1.

OBJECTIVE: The inability to properly process visual information has been frequently associated with neurofibromatosis type 1 (NF1). Based on animal studies, the cause of cognitive disabilities in NF1 is hypothesized to arise from decreased synaptic plasticity. Visual cortical plasticity in humans can be investigated by studying visual evoked potentials (VEPs) in response to visual stimulation. METHODS: VEP plasticity was assessed by measuring the increase of the peak amplitudes C1, P1, and N1 induced by 10-min modulation of checkerboard reversals in 22 adult NF1 patients and 30 controls. VEP signals were recorded pre-modulation, during modulation, and at 2, 7, 12, 17, 22, 27 min post-modulation. RESULTS: The P1 amplitude increased significantly comparing post-modulation to pre-modulation in the control group. This potentiation was not observed in the NF1 group. CONCLUSIONS: Visual cortical plasticity could be measured using VEPs in response to visual stimulation in the control group. Individuals with NF1 may have reduced visual cortical plasticity, as indicated by their non-potentiated response to VEP induction. These findings should be interpreted with caution due to high inter-subject variability. SIGNIFICANCE: The present study contributes to an improved assessment of the feasibility for using neurophysiological outcome measures in intervention studies of cognitive deficits among patients with NF1.

Sleep monitoring by actigraphy in short-stay ICU patients.

Sleep deprivation is common in intensive care unit (ICU) patients. The criterion standard for sleep monitoring, polysomnography, is impractical in ICU. Actigraphy (a wrist watch indicating amount of sleep) proved to be a good alternative in non-ICU patients, but not in prolonged mechanically ventilated patients, probably due to ICU-acquired weakness. Short-stay ICU patients do not suffer from ICU-acquired weakness. However, the accuracy of actigraphy is unknown in these patients. Therefore, we compared actigraphy to polysomnography in short-stay ICU patients. Sleep measurements were conducted in 7 postcardiothoracic surgery patients. The sensitivity (percentage of actigraphy data that agreed with sleep determined using polysomnography) and specificity (percentage of actigraphy data that agreed with awake determined using polysomnography) were calculated. The result showed that actigraphy underestimated the amount of wake time and overestimated the amount of sleep. The median specificity for actigraphy was always less than 19% and sensitivity more than 94%. Therefore, actigraphy is not reliable for sleep monitoring in short-stay ICU patients.

Drug-free patients with major depression show an increased electrophysiological response to valid and invalid feedback.

BACKGROUND: Depressed patients are biased in their response to negative information. They have been found to show a maladaptive behavioral and aberrant electrophysiological response to negative feedback. The aim of this study was to investigate the behavioral and electrophysiological response to feedback validity in drug-free depressed patients. METHOD: Fifteen drug-free in-patients with unipolar major depression disorder (MDD) and 30 demographically matched controls performed a time-estimation task in which they received valid and invalid (i.e. related and unrelated to performance) positive and negative feedback. The number of behavioral adjustments to the feedback and the feedback-related negativity (FRN) were measured. RESULTS: Patients made fewer correct adjustments after valid negative feedback than controls, and their FRNs were larger. Neither patients nor controls adjusted their time estimates following invalid negative feedback. CONCLUSIONS: The FRN results suggest that depressed drug-free in-patients have an atypical rostral anterior cingulate response to feedback that is independent of feedback validity. Their behavioral response to invalid negative feedback, however, is not impaired. This study confirms the notion that the behavioral responses of depressed individuals to negative feedback are context dependent.

[The neurobiology of antisocial behaviour]. / Neurobiologische aspecten van antisociaal gedrag.

BACKGROUND: Neuro-imaging is being used increasingly to provide explanations for antisocial behaviour. AIM: To make a neurobiological contribution to the diagnosis of many types of antisocial behaviour. METHOD: The literature was searched using PubMed and combinations of the keywords 'psychopathy', 'antisocial', 'neurobiology' and 'neuro-anatomy' for the period 1990-2009. RESULTS: Impairments in the prefrontal cortex, amygdala, hippocampus, superior temporal gyrus, corpus callosum and anterior cingulate cortex provide a possible explanation for a large number of the symptoms associated with antisocial behaviour. The concept of psychopathy is connected mainly with impairments in a prefrontal-temporal-limbic system. CONCLUSION Combinations of deficiencies in the associated brain areas and malfunctioning of the communication between the various brain structures seem to play a more important role than deficiencies in the separate brain structures.

Cardiovascular variability during treatment with haloperidol, olanzapine or risperidone in recent-onset schizophrenia.

This study aimed to investigate the effects of treatment with haloperidol, olanzapine and risperidone on cardiovascular variability in patients with recent-onset schizophrenia by means of spectral analysis. Unmedicated patients (n = 18) had a higher mean heart rate and a tendency for a lower high-frequency power of heart rate variability than healthy control subjects (n = 57), indicating a decreased cardiac vagal control in unmedicated patients with schizophrenia. Patients treated with haloperidol (n = 10) showed significantly lower low-frequency power of heart rate and systolic blood pressure variability compared with olanzapine-treated patients, suggesting that haloperidol attenuated sympathetic functioning. On the contrary, olanzapine-treated patients (n = 10) showed the highest power in the low-frequency range of heart rate and systolic blood pressure variability, suggesting an increased sympathetic cardiac functioning. No significant effects of risperidone (n = 13) were found. None of the antipsychotic agents differed in their parasympathetic cardiovascular effects. We conclude that young, unmedicated patients with schizophrenia differed from controls in their parasympathetic functioning, but the antipsychotic agents haloperidol, risperidone and olanzapine induced only minor cardiovascular side effects.

Actigraphic sleep duration and fragmentation are related to obesity in the elderly: the Rotterdam Study.

OBJECTIVE: The epidemiological evidence for the association between sleep duration and obesity in the elderly is inconsistent and has not been investigated with objective measures. Furthermore, the role of sleep fragmentation in this relationship is unknown. Our aim was to investigate the association of sleep measures with body mass index (BMI) and obesity in a normal elderly population. DESIGN: Cross-sectional study. SUBJECTS: A total of 983 community-dwelling elderly (mean age 68.4+/-6.9 years, range, 57-97). MEASUREMENTS: Weight and height were measured, and sleep duration and fragmentation were assessed with on average six nights of actigraphy. RESULTS: A quadratic model adequately described the association between continuous measures of sleep duration and BMI. Actigraphic sleep duration had a significant U-shaped relationship with BMI (beta of quadratic term=0.30, 95% confidence interval (CI): 0.08, 0.52). Both short sleepers (<5 h: OR, 2.76 (95% CI: 1.38, 5.49), 5 to <6 h: OR, 1.97 (95% CI: 1.26, 3.08)) and long sleepers (>or=8 h: OR, 2.93 (95% CI: 1.39, 6.16)) were more likely to be obese, compared to participants who slept 7 to <8 h. BMI increased with 0.59 kg m(-2) per standard deviation of sleep fragmentation (95% CI: 0.34, 0.84). After adjustment for sleep fragmentation, the association between short sleep and obesity was no longer significant. Exclusion of participants with probable sleep apnea only marginally changed these associations. Self-reported habitual sleep duration was not associated with BMI or obesity. CONCLUSIONS: Sleep duration, as measured with actigraphy, had a U-shaped relationship with BMI and obesity in an elderly population. A highly fragmented sleep is associated with a higher BMI and a higher risk of obesity, and may explain why short sleep is related to obesity. To preclude bias that can be introduced by self-report measures of sleep duration, using multiple measures of sleep parameters is recommended in future research.

Associations between HPA axis functioning and level of anxiety in children and adolescents with an anxiety disorder.

The hypothalamus-pituitary-adrenal (HPA) axis becomes active in response to stress. Hence, increased levels of anxiety in children and adolescents may be associated with changes in HPA-axis functioning. The aim of this study was to test if level of anxiety or specific anxiety disorders were associated with basal HPA axis activity in children and adolescents with an anxiety disorder. In 99 8- to 16-year-olds with an anxiety disorder, basal cortisol levels were assessed. It was tested if (1) cortisol levels correlated with the level of self-reported anxiety and (2) if cortisol levels were different for individuals with different anxiety disorders. In girls, low levels of anxiety were associated with a stronger rise in early morning cortisol concentrations. In both boys and girls, harm avoidance predicted low cortisol concentrations after awakening. Separation anxiety and physical anxiety symptoms predicted cortisol concentrations at noon. Differences between individuals with different anxiety disorders were not found. More research is needed regarding mechanisms that explain the associations that were found, and to investigate if treatment may influence HPA axis functioning in children and adolescents with an anxiety disorder.

[Psychiatric and neuropsychological characterization of a group of adults referred to a university outpatient clinic for ADHD]. / Psychiatrische en neuropsychologische kenmerken van een groep volwassenen verwezen naar een academische polikliniek voor ADHD.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) has always been classified as a psychiatric disorder of childhood. Very little research has been done into the nature of adult ADHD. AIM: To obtain insight into the clinical profile of a group of adults referred to an outpatient clinic for diagnostic assessment of ADHD. METHOD: A group of 225 adults diagnosed with ADHD were studied and compared with 101 adults who had been referred to the same outpatient clinic but had been given a different diagnosis. All referred patients were diagnosed according to dsm-iv criteria for ADHD and underwent neuropsychological tests. RESULTS: The diagnosis of ADHD was confirmed in 69% of the patients. In the ADHD group 72% were male and the average age was 32. Half of these patients had a co-morbid disorder. The 2 groups did not differ in psychopathology but the ADHD group used nicotine and alcohol more frequently. Neuropsychological tests revealed more signs of subjective distractibility in the non-ADHD group, whereas in the objective tests it was the ADHD group who gave a poorer performance. CONCLUSION: This study describes the clinical profile of a group of adults referred to an outpatient clinic for ADHD. The ADHD group differed from the non-ADHD group in a number of demographical, psychiatric and neuropsychological parameters.

Early attention processes and anxiety in children.

It has been hypothesized that anxiety in children is associated with attentional bias in the early stages of information processing. Bias towards threat indicates the tendency of an individual to direct attention towards threatening information. The aim of the present study was to investigate whether high test-anxiety in a sample of nonreferred children is associated with attentional bias towards threat pictures, and if low test-anxiety is associated with attentional bias away from threat pictures. A probe-detection task was used with 44 10- to 13-yr.-old children. The overall analyses indicated the presence of an attentional bias away from threatening pictures in these nonreferred children. However, in relation to anxiety, the study did not confirm that high anxious children show an attentional bias towards threatening pictures or that low anxious children show an attentional bias away from threatening pictures. Yet, higher anxiety did seem to be associated with longer mean response times. These longer response times might originate from the interpretation of the nature of a stimulus as too threatening, compared to the actual threatening content, in the first stage of information processing. This finding could be useful to improve treatment methods aimed at anxiety symptoms during childhood.

Quantification of the dynamic behavior over time of narrow-band components present in heart rate variability by means of the instantaneous amplitude and frequency.

The statistical properties of the time- and frequency-domain characteristics of heart rate variability are known to vary over time. A method is presented to compute the time-varying spectral contents of the characteristic narrow-band frequency components of heart rate variability by means of the instantaneous amplitude and frequency at an optimal time resolution. The instantaneous frequency may show oscillatory, but also irregular periods in time. An index of the instantaneous bandwidth is computed to discriminate between oscillatory and irregular periods and to correct the instantaneous amplitude and frequency for irregular periods.

Cardiovascular risk factors in outpatients with bipolar disorder.

BACKGROUND: The mortality due to cardiovascular diseases in bipolar patients is much higher than in the general population. It is unclear whether lithium treatment contributes to this cardiovascular morbidity. METHODS: The cardiovascular risk factors in outpatients with bipolar disorder on monotherapy lithium were explored. Cardiac (family) history, important habits and recent stressful events were assessed. Quetelet Index (QI) was calculated and blood samples were taken. Blood pressure (BP) was measured in supine position and during orthostatic challenge. RESULTS: 40 out of 81 patients on monotherapy lithium were studied in detail. In this group, one patient was hypothyroid; six patients suffered from hypertension. QI was > 25 in 57.5% of the patients; mean cholesterol level was 5.7 mmol/L. Renal functioning, electrolytes and glucose concentrations were normal. There were no significant relationships between the duration of lithium treatment, the duration of bipolar disorder, recent stressful events and hypertension. Out of the group of 81 patients on lithium monotherapy, 13 patients in total used antihypertensive medication, indicating a high prevalence of hypertension in this group as compared to the general population. CONCLUSIONS: Cardiovascular risk factors, including hypertension, were increased in a large proportion of this population on monotherapy lithium. However, no significant relationships were observed between duration of lithium treatment or bipolar disorder and presence of hypertension.

Low body mass index is associated with an increased risk of neuropsychiatric adverse events and concentration impairment in women on mefloquine.

AIMS: We performed a prospective cohort study to gain more insight into risk factors for neuropsychiatric effects of mefloquine among tourists travelling to tropical areas. METHODS: We enrolled all patients who consulted the Travel Clinic of the Havenziekenhuis & Institute for Tropical Diseases Rotterdam for mefloquine prophylaxis during the period between 1 May 1999 and 7 March 2000. Each patient was followed from baseline (prior to starting mefloquine) up to 3 weeks after starting weekly intake of 250 mg mefloquine. We compared the intraindividual change in scores between baseline and follow-up visit on the Dutch shortened Profile of Mood States, and on the Continuous Performance Test (CPT) which measures sustained attention. RESULTS: The final cohort consisted of 151 subjects with a mean age of 38 years. In this population, a significant impairment of mood state was observed in those with a body mass index (BMI) < or = 20 kg m(-2). Stratification for gender showed that the total mood disturbance in females in the lowest BMI category significantly increased by 8.42 points [95% confidence interval (CI) 3.33, 13.50], whereas BMI did not affect the risk in males. Stratification for history of use of mefloquine showed that the risks were highest in first-time users. Analyses of the CPT showed that reaction time in women with a BMI < or = 20 kg m(-2) increased significantly by 22.5 ms (95% CI 7.80, 37.20), whereas reaction time in men showed a slight and nonsignificant decrease. CONCLUSION: Risk factors for mefloquine-associated neuropsychiatric adverse events and concentration impairment are female gender, low BMI, and first-time use. The frequency of neuropsychiatric effects is highest in women with a BMI < or = 20 kg m(-2).

Interictal daily functioning in migraine.

Migraine induces disability and an impaired quality of life, even between attacks. As most studies are based on subjective reports only, this study was set up to objectively quantify the interictal daily activities and heart rate of migraine patients, in relation to their subjectively reported highest realizable level of activity and of symptoms of mood in their habitual environment. Measurements were obtained during a migraine-free 2-day period of 24 patients (age range: 21-57 years) and 24 controls (age range: 18-59 years). Accelerometry was used to quantify the time spent in different postures and movements. The subjective parameters were documented by daily log. Whereas heart rate was similar for patients and controls, migraineurs were found to be significantly less physically active than controls and reported a significantly lower realizable level of activity. In addition, when active, their body motility was less than that of controls. Migraine patients also showed a higher level of sleepiness and lower level of vigour. These interictal behavioural and subjective phenomena objectively illustrate the individual and societal burden of migraine and its chronic impact on both domains.

Effects of imipramine, fluvoxamine and depressive mood on autonomic cardiac functioning in major depressive disorder.

OBJECTIVE: Diminished HR variability is considered to be associated with depression and the increased risk of cardiovascular disease. The pharmacological effects of antidepressants and depressive mood itself may contribute to alterations in autonomic cardiac functioning, but a limited amount of data is available. We studied the effects of two different types of antidepressant treatments (imipramine and fluvoxamine), in addition to the effect of depressive mood, on the cardiovascular system in depressed patients. METHODS: Depressed inpatients were studied during a drug-free period and after 4 weeks of adequate treatment with imipramine (n = 17) or fluvoxamine (n = 24). Heart rate variability, blood pressure variability, and a baroreflex sensitivity index during supine rest and orthostatic challenge were analyzed by means of spectral techniques to obtain noninvasive parameters of sympathetic and parasympathetic activity. RESULTS: Both imipramine and fluvoxamine reduced sympathetic and parasympathetic activity, although the effects of imipramine were much more pronounced. Severity of depression was positively related to mean levels of heart rate and blood pressure in the total patient group. There was no convincing evidence that these relationships differed between depressed patients treated with imipramine and those treated with fluvoxamine. CONCLUSION: Our findings suggest that alterations in mean heart rate and blood pressure in depressed patients after antidepressant treatment are the result of a combined effect of pharmacological actions of antidepressants and improvement of depressive mood state. The present study did not confirm the relationship between clinical state and cardiovascular variability or baroreflex sensitivity.

The instantaneous frequency of cardiovascular time series: a comparison of methods.

The instantaneous frequency (IF) of cardiovascular time series is used to describe the time-varying spectral contents of the characteristic frequency bands that are of interest for psychophysiological and cardiovascular research. Four methods to compute IF of band-limited, monocomponent, and analytical cardiovascular time series were compared by means of simulated time series contaminated with additive noise. These four methods are: the method using the inverse Fourier transform of uncorrelated time-slices of the Wigner-Ville distribution, the discrete time-frequency transform, the circular mean direction of the time-slices of the Wigner-Ville distribution, and the central finite difference of the phase. The time resolution of the estimates is optimal and is inversely related to the bandwidth of the frequency components, as given by the uncertainty principle of Gabor. At periods in time where the signal fulfills the requirements of the model signal, the four estimates of IF are numerically equal; only the circular mean direction showed a slight deviation from the other estimates. Although the estimates of IF differ at sudden phase shifts at low amplitude, i.e. at points where the signal locally does not comply with the requirements of the model signal, overall the four methods produce comparable estimates of IF of a cardiovascular time series at an optimal time resolution.

Neuropsychiatric events during prophylactic use of mefloquine before travelling.

INTRODUCTION: It has been suggested that neuropsychiatric events during use of mefloquine are more common in females than in males and are partly explained by the psychological stress of travelling. Therefore, we investigated neuropsychiatric events in females and males on mefloquine in the 3-week prophylactic period that precedes travelling. Furthermore, we investigated whether first-time users had a higher risk of neuropsychiatric adverse events than subjects with a history of mefloquine use. METHODS: We enrolled all patients who visited a Travel Clinic for mefloquine prophylaxis during the period 1 May 1999 to 7 March 2000. Each patient was followed from baseline (prior to starting mefloquine) up to 3 weeks after the start of mefloquine but before travelling. We asked patients to register any adverse event in a diary and measured the intra-individual change in scores on the Dutch Shortened Profile Of Mood States (POMS) at baseline and at the end of follow-up. RESULTS: The final cohort consisted of 179 subjects with a mean age of 3 years. Females reported adverse events more frequently than males ( P=0.005). Overall, we observed a small but significant increase in the score on the domain fatigue [0.74 points, 95% confidence interval (CI) 0.18, 1.30]. The effect was exclusively present in females and not in males. First-time users of mefloquine increased 2.81 points (95% CI 0.70, 4.92) on the total score of the POMS, and among those, women showed the largest increase of 4.58 points (95% CI 0.74, 8.43). CONCLUSION: The use of mefloquine was associated with neuropsychiatric adverse effects. Females encountered neuropsychiatric effects more frequently than males, which could be confirmed by validated psychological tests. Neuropsychiatric effects were more common in first-time users than in individuals who had used mefloquine before.

Spectral analysis of heart rate and blood pressure variability in primary Sjögren's syndrome.

BACKGROUND: Autonomic dysfunction has been described in primary Sjögren's syndrome (SS). OBJECTIVE: To investigate the circulatory autonomic regulation in patients with primary SS by power spectral analysis of heart rate and blood pressure variability. METHODS: Forty three (42 female) patients with primary SS, mean age 52 years (range 23-80), with a mean disease duration of eight years (range 1-30) and 30 (15 female) healthy controls, mean age 43 years (range 21-68) were studied. In each patient blood pressure, heart rate, and respiration were measured continuously during supine rest and orthostatic challenge (60 degrees head-up tilt). Power spectral analysis was performed to determine possible differences in short term sympathetic and parasympathetic autonomic regulation between patients and controls. Furthermore, spectral parameters were studied in relation to illness severity and disease duration of the patients with primary SS. RESULTS: After controlling for differences in age, heart rate variability of the mid-frequency band and the variation coefficient of systolic blood pressure were significantly lower in patients with primary SS than in controls during supine rest. During 60 degrees tilt patients with primary SS showed a significantly higher mean heart rate, mean systolic blood pressure, and variation coefficient of diastolic blood pressure, and a significantly lower baroreflex index than controls. After controlling for age, no differences were found either in heart rate variability, blood pressure results, and baroreflex sensitivity during supine rest and tilt between the subgroups divided according to disease duration, Schirmer test results, or between the subgroups with different fatigue scores. No differences were found in spectral data between the groups with and without positive antinuclear antibody serology. CONCLUSION: For the group no differences in sympathetic and parasympathetic cardiac control were seen between patients with primary SS and controls, as assessed by spectral techniques, although some cardiovascular differences were found, particularly during orthostatic challenge.

Measuring daily behavior using ambulatory accelerometry: the Activity Monitor.

Advanced ambulatory systems that measure aspects of overt human behavior during normal daily life have become feasible, owing to developments in data recording and sensor technology. One such instrument is the Activity Monitor (AM). This paper provides a technical description of the AM and information about its validity and current applications. The AM is based on ambulatory accelerometry, the aim of which is to assess postures and motions for long-term (> 24-h) measurement periods during normal daily life. Accelerometers are attached to the thighs, trunk, and lower arms, and signals are continuously stored in a digital portable recorder. In the postmeasurement analysis, postures and motions are detected by means of custom-made software programs. Validity studies performed on different populations showed high agreement scores between the computerized and automatic AM output and the visually analyzed video recordings. The AM has so far been applied in rehabilitation, psychophysiology, and cardiology but has many possibilities in behavioral research.