RATIONALE\nThe specific role of neuromodulator systems in regulating rapid fluctuations of attention is still poorly understood.\nOBJECTIVES\nIn this study, we examined the effects of clonidine and... Show moreRATIONALE\nThe specific role of neuromodulator systems in regulating rapid fluctuations of attention is still poorly understood.\nOBJECTIVES\nIn this study, we examined the effects of clonidine and scopolamine on multiple target detection in a rapid serial visual presentation task to assess the role of the central noradrenergic and cholinergic systems in temporal attention.\nMETHOD\nEighteen healthy volunteers took part in a crossover double-dummy study in which they received clonidine (150/175 μg), scopolamine (1.2 mg), and placebo by mouth in counterbalanced order. A dual-target attentional blink task was administered at 120 min after scopolamine intake and 180 min after clonidine intake. The electroencephalogram was measured during task performance.\nRESULTS\nClonidine and scopolamine both impaired detection of the first target (T1). For clonidine, this impairment was accompanied by decreased amplitudes of the P2 and P3 components of the event-related potential. The drugs did not impair second-target (T2) detection, except if T2 was presented immediately after T1. The attentional blink for T2 was not affected, in line with a previous study that found no effect of clonidine on the attentional blink.\nCONCLUSIONS\nThese and other results suggest that clonidine and scopolamine may impair temporal attention through a decrease in tonic alertness and that this decrease in alertness can be temporarily compensated by a phasic alerting response to a salient stimulus. The comparable behavioral effects of clonidine and scopolamine are consistent with animal studies indicating close interactions between the noradrenergic and cholinergic neuromodulator systems. Show less
Warren, C.M.; Eldar, E.; Brink, R.L. van den; Tona, K.D.; Van der Wee, N.J.; Giltay, E.J.; ... ; Nieuwenhuis, S. 2016
Background: In Huntington’s disease (HD) the innate immune system is activated, as reflected by increased plasma levels of different cytokines.Objective: To explore whether increased cytokine... Show moreBackground: In Huntington’s disease (HD) the innate immune system is activated, as reflected by increased plasma levels of different cytokines.Objective: To explore whether increased cytokine levels are associated with neuropsychiatric symptoms and cognitive dysfunction in HD mutation carriers.Method: Plasma cytokine levels of TNF-alpha, interleukin (IL)-1ra, IL-1β, IL-5, IL-6, IL-8 and Il-10 were assessed in 124 HD mutation carriers at two time points 2 years apart (totalling 214 observations). Using multilevel regression analysis, cytokines were analysed in relation to neuropsychiatric symptoms and cognitive dysfunction. Depressed mood was assessed with the depression subscale of the Problem Behaviours Assessment (PBA), apathy with the Apathy Scale, and irritability with the Irritability Scale. Cognitive functioning was assessed using the Mini-Mental State Examination (MMSE) and a battery of executive cognitive functioning tests, aggregated into an executive cognitive functioning (ExCog) score.Results: Inverse associations were found in adjusted models between IL-6 and ExCog score (β= –0.114; p = 0.01) and between IL-1ra and ExCog score (β= –0.110; p = 0.02). No associations between cytokine levels and any of the other neuropsychiatric symptom scores remained statistically significant in adjusted models.Conclusion: Higher plasma levels of IL-6 and IL-1ra are weakly associated with cognitive dysfunction in HD, but not with other neuropsychiatric symptoms. Show less
Brown, S.B.R.E.; Wee, N.J.A. van der; Noorden, M.S. van; Giltay, E.J.; Nieuwenhuis, S. 2015
Researchers have proposed several hypotheses about the neuromodulator systems involved in generating P3 components of the ERP. To test some of these hypotheses, we conducted a randomized placebo... Show moreResearchers have proposed several hypotheses about the neuromodulator systems involved in generating P3 components of the ERP. To test some of these hypotheses, we conducted a randomized placebo-controlled crossover study in which we investigated how the late positive ERP response to deviant stimuli is modulated by (a) clonidine, an α2 agonist that attenuates baseline noradrenergic activity; and (b) scopolamine, a muscarinic antagonist of acetylcholine receptors. We collected EEG data from 18 healthy volunteers during the performance of an auditory oddball task with several active and passive task conditions. We then used temporospatial principal component analysis (PCA) to decompose the ERP waveforms. The PCA revealed two distinct late positive ERP components: the classic parietal P300 and the frontal novelty P3. Statistical analysis of the temporospatial factor scores indicated that in most conditions the amplitude of the classic P300 was increased by clonidine and scopolamine. In contrast, the amplitude of the novelty P3 was decreased by both drugs. The similar pattern of results for clonidine and scopolamine probably reflects the strong interactions between the noradrenergic and cholinergic systems. The results, in combination with previous pharmacological studies, suggest a critical role for both neuromodulator systems in the generation of the P300 and the novelty P3. Show less
