Objective: It remains unclear whether daytime impairments in ADHD patients are better explained by an altered level of alertness and/or by cognitive deficits. The aim of this study was to determine ...the respective contribution of these factors on driving performance in ADHD adults. Method: ADHD adults (n = 39) and healthy controls (n = 18) underwent a nocturnal polysomnography (PSG) followed by a Maintenance of Wakefulness Test (MWT), a simulated driving task, and a neuropsychological evaluation. Results: ADHD patients had shorter mean sleep latency on the MWT and worse driving performance than controls. They also made more errors on attention and executive functioning tests. Logistic regression analyses showed that inhibition deficits and objective daytime sleepiness predicted highway driving performance in ADHD. Conclusion: Our study shows that not only inhibitory control deficits but also pathological level of alertness independently contribute to highway driving impairment in ADHD patients, providing a better understanding of the pathophysiological mechanisms involved in ADHD.
Although subjective complaints about daytime cognitive functioning are an essential symptom of chronic insomnia, abnormalities in functional brain activation have not previously been investigated. ...This study was designed to investigate functional brain activation differences as a possible result of chronic insomnia, and the reversibility of these differences after nonmedicated sleep therapy.
Insomniacs and carefully matched controls underwent functional magnetic resonance imaging (fMRI) scanning during the performance of a category and a letter fluency task. Insomniacs were randomly assigned to either a 6-week period of nonpharmacological sleep therapy or a wait list period, after which fMRI scanning was repeated using parallel tasks. Task-related brain activation and number of generated words were considered as outcome measures.
The outpatient sleep clinic of the VU University Medical Center, Department of Clinical Neurophysiology; fMRI was performed at the Department of Radiology.
Twenty-one patients suffering from chronic insomnia and 12 matched controls.
Nonpharmacological sleep therapy for 6 weeks, consisting of cognitive behavioral therapy, body temperature and bright light interventions, sleep hygiene, and physical activity counseling.
Compared to controls, insomnia patients showed hypoactivation of the medial and inferior prefrontal cortical areas (Brodmann Area 9, 44-45), which recovered after sleep therapy but not after a wait list period.
Insomnia interferes in a reversible fashion with activation of the prefrontal cortical system during daytime task performance.
We have previously shown that patients with Parkinson's disease (PD) perseverate in their choice of action relative to healthy controls, and that this is affected by dopaminergic medication (Hughes ...LE, Barker RA, Owen AM, Rowe JB. 2010. Parkinson's disease and healthy aging: Independent and interacting effects on action selection. Hum Brain Mapp. 31:1886-1899). To understand further the neural basis of these phenomena, we used a new task that manipulated the options to repeat responses. Seventeen patients with idiopathic PD were studied both "on" and "off" dopaminergic medication and 18 healthy adults were scanned twice as controls. All subjects performed a right-handed 3-choice button press task, which controlled the availability of repeatable responses. The frequency of choosing to repeat a response (a form of perseveration) in patients was related to dopamine therapy and disease severity as a "U-shaped" function. For repetitive trials, this "U-shaped" relationship was also reflected in the BOLD response in the caudate nuclei and ventrolateral prefrontal cortex. Our results support a U-shaped model of optimized cortico-striatal circuit function and clearly demonstrate that flexibility in response choice is modulated by an interaction of dopamine and disease severity.
Emotional reactivity in insomnia is affected both subjectively and on a physiological level for negative emotional material, but little is known about reactions to positive stimuli. We here ...investigated whether in younger adult insomnia patients, presentation of short humorous films would lead to heart rate decreases during and after film viewing, as compared to heart rate changes when falling asleep. Investigating 20 participants with DSM‐5‐diagnosed insomnia and 18 participants without insomnia, we found that heart rate decreased when falling asleep, increased when watching humorous films and returned to normal values afterwards for all participants. Film‐related heart rate increases were strongly related to humour ratings of the films. No differences were found between those with and without insomnia on subjective ratings of the films, film‐related heart rate changes or when falling asleep. We conclude that the experience of positive daily life stimuli in younger adults is not affected by insomnia in our study, despite insomnia having a known more profound effect on negative stimuli. Future studies exploring insomnia‐related autonomous nervous system responses combining different neurophysiological modalities should confirm our findings.
Background Chronic insomnia is a poorly understood disorder. Risk factors for developing chronic insomnia are largely unknown, yet disturbances in brain indexes of arousal seem to accompany the ...disorder. We here investigate whether insomnia patients and control participants differ with respect to brain responses to direct stimulation, i.e., cortical excitability. Transcranial magnetic stimulation (TMS) offers a method to directly investigate the excitability level of the human cerebral cortex in psychiatric and neurological disease. Methods We investigated cortical excitability in 16 insomnia patients and 14 carefully matched control participants using absolute and relative amplitudes of motor evoked potentials in response to single- and paired-pulse stimulation using TMS. Results Nonmedicated insomnia patients showed, first, an exaggerated absolute response to both suprathreshold single- and paired-pulse stimulation compared with control participants and second, a reduced relative response to paired-pulse stimulation at long interpulse intervals (i.e., a reduced intracortical facilitation). The abnormal excitability persisted despite sleep therapy that effectively improved sleep quality as well as behavioral and neuroimaging indexes of brain function. Conclusions The results suggest that a subtly disturbed intracortical excitability characterizes patients with chronic insomnia: a relatively reduced intracortical facilitation in the context of a globally increased absolute excitability. The findings do not resemble TMS findings after sleep deprivation or in sleep apnea and thus seem specific to insomnia. They may offer diagnostic value and implications for assessment of risk to develop this common and disabling disorder.
To examine brain activation patterns during verbal fluency performance in patients with progressive muscular atrophy (PMA) and amyotrophic lateral sclerosis (ALS).
fMRI was used to examine the blood ...oxygen level-dependent response during letter and category fluency performance in 18 patients with PMA, 21 patients with ALS, and 17 healthy control subjects, matched for age and education. fMRI results are reported at p<0.05, family-wise error (FWE)-corrected for multiple comparisons. We analyzed effects of performance, age-related white matter changes (ARWMC), and regional brain volumes; all participants underwent neuropsychological investigation.
Disease duration of patients with PMA (mean 26.0 months, SD 13.6) and ALS (22.2 months, SD 11.4) was comparable. Patients with PMA and ALS had mild to moderate disease severity and showed impaired letter fluency compared with controls. Between-group analysis showed a main effect of group in the left inferior frontal gyrus (IFG, Brodmann area 45) during letter fluency, which was unaffected by performance, ARWMC, and IFG volume: patients with PMA showed lower activation than controls but higher than that of patients with ALS (ALS<PMA<healthy controls; pFWE=0.035; z score 4.11; cluster size=11). A more caudal region in the IFG showed lower activation in patients with PMA than controls during letter fluency performance (post hoc test; pFWE=0.026). No activation differences were observed during the category fluency task.
Prefrontal activation abnormalities are related to an important clinical measure of executive dysfunction in patients with motor neuron disease with and without upper motor neuron signs.
Hyperarousal is a 24-h state of elevated cognitive and physiological activation, and is a core feature of insomnia. The extent to which sleep quality is affected by stressful events-so-called sleep ...reactivity-is a vulnerability factor for developing insomnia. Given the increasing prevalence of insomnia with age, we aimed to investigate how hyperarousal and sleep reactivity were related to insomnia severity in different adult age groups. Data were derived from a large cohort study investigating the natural history of insomnia in a population-based sample (
= 1693). Baseline data of the Arousal Predisposition Scale (APS) and Ford Insomnia Response to Stress Test (FIRST) were examined across age and sleep/insomnia subgroups: 25-35 (
= 448), 35-45 (
= 528), and 45-55 year olds (
= 717); good sleepers (
= 931), individuals with insomnia symptoms (
= 450), and individuals with an insomnia syndrome (
= 312). Results from factorial analyses of variance (ANOVA) showed that APS scores decreased with increasing age, but increased with more severe sleep problems. FIRST scores were not significantly different across age groups, but showed the same strong increase as a function of sleep problem severity. The findings indicate that though arousal predisposition and sleep reactivity increase with more severe sleep problems, only arousal decreases with age. How arousing events affect an individual during daytime thus decreases with age, but how this arousal disrupts sleep is equivalent across different adult age groups. The main implication of these findings is that treatment of insomnia could be adapted for different age groups and take into consideration vulnerability factors such as hyperarousal and stress reactivity.
Introduction
Amyloid plaque deposition in the brain is an early pathological change in Alzheimer's disease (AD), causing disrupted synaptic connections. Brain network disruptions in AD have been ...demonstrated with eigenvector centrality (EC), a measure that identifies central regions within networks. Carrying an apolipoprotein (APOE)‐ε4 allele is a genetic risk for AD, associated with increased amyloid deposition. We studied whether APOE‐ε4 carriership is associated with EC disruptions in cognitively normal individuals.
Methods
A total of 261 healthy middle‐aged to older adults (mean age 56.6 years) were divided into high‐risk (APOE‐ε4 carriers) and low‐risk (noncarriers) groups. EC was computed from resting‐state functional MRI data. Clusters of between‐group differences were assessed with a permutation‐based method. Correlations between cluster mean EC with brain volume, CSF biomarkers, and psychological test scores were assessed.
Results
Decreased EC in the visual cortex was associated with APOE‐ε4 carriership, a genetic risk factor for AD. EC differences were correlated with age, CSF amyloid levels, and scores on the trail‐making and 15‐object recognition tests.
Conclusion
Our findings suggest that the APOE‐ε4 genotype affects brain connectivity in regions previously found to be abnormal in AD as a sign of very early disease‐related pathology. These differences were too subtle in healthy elderly to use EC for single‐subject prediction of APOE genotype.
Decreased functional brain eigenvector centrality measured from fMRI was associated with APOE genotype, a genetic risk factor for Alzheimer's disease. Changes were found in the visual cortex, posterior cingulate, and precuneus.
The cognitive changes that occur with ageing are usually referred to as 'age-related cognitive decline'. The most pronounced changes may be found in the executive functions that require integrity of ...the prefrontal cortical circuitry. With age, sleep also changes profoundly, with more sleep fragmentation, earlier awakenings and less slow wave sleep as its main features. Interestingly, experimental sleep deprivation studies in healthy young adults showed a particularly consistent effect on executive functions, suggesting that sleep problems might contribute to the cognitive changes accompanying older age. We here investigate this possibility by reviewing reports on age-related and insomnia-related changes in cognition and brain function and structure, as found in studies investigating subjective complaints, objective functioning in everyday life, neuropsychological assessment, psychometry, structural and functional magnetic resonance imaging, electroencephalography, positron emission tomography and transcranial magnetic stimulation. The chapter focuses on the 'normal' age-related sleep changes that are experienced as insomnia - that is, fragmentation of sleep, more superficial sleep, more wake after sleep onset and earlier awakenings - rather than on specific sleep disturbances as sleep-disordered breathing, restless legs or periodic limb movements during sleep, for all of which the risk increases with age. It turned out that relatively few studies directly addressed the question whether elderly with different degrees of sleep complaints are differentially affected by 'age-related cognitive decline'. Still, several similarities between age-related and insomnia-related cognitive and brain changes are apparent, notably with respect to performance requiring integrity of the prefrontal cortical system. We suggest that at least part of what we regard as age-related changes may, in fact, be due to poor sleep, which is in some cases a treatable condition. Further research directly comparing aged good sleepers versus aged insomniacs will need to elucidate how sleep disturbances are involved in the cognitive, structural and functional changes observed with increasing age. The findings suggest that discrimination of subtypes of poor sleep at high age will aid in understanding the mechanisms by which it affects cognition and brain function.
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