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ABSTRACT: The late positive components of the human event-related brain potential comprise electrocortical reflections of stimulus-driven attentional capture (the anteriorly distributed P3a) and top-down control detection of relevant events (the posteriorly distributed P3b). As of yet, the neuropharmacologic and neurogenetic origin of the P3a and P3b is not fully understood. In this study, we address the contribution of dopaminergic and serotoninergic mechanisms. Sixty healthy females completed an active auditory novelty oddball paradigm while EEG was recorded. In all subjects, genetic polymorphisms within the dopamine system (dopamine transporter [DAT1], catecholamine-O-methyltransferase val158met [COMT val158met]) and the serotonin system (serotonin transporter [5HTTLPR]) were assessed. Across genotypes, novels (relative to standards) elicited a fronto-centrally distributed P3a, and targets (relative to standards) a parieto-centrally distributed P3b. Genotypes effects were observed for both P3a (COMT, 5HTTPLR) and P3b (DAT1, COMT, 5HTTLPR) only at prefrontal electrode location (Fz). Specifically, the frontal P3a was enhanced in COMT met/met homozygotes, but not in DAT1 9R. The target-related P3b was enhanced in COMT met/met and DAT1-9R relative to its genetic counterparts, but only at frontal electrodes. This 'anteriorized' enhancement may reflect either an additional frontal component in the target-related P3 dependent on dopamine, or a more subtle shift in the neural ensemble that generates the target-related P3. Results for 5HTTLPR short allele homozygotes mimicked those in COMT met/met homozygotes. In all, the present findings suggest involvement of frontal-cortical dopaminergic and serotoninergic mechanisms in bottom-up attentional capture (COMT val158met, 5HTTLPR), with an additional top-down component sensitive to striatal signals (DAT1).
Behavioural brain research 04/2013; · 3.22 Impact Factor
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ABSTRACT: Genetic differences in the dopamine and serotonin systems have been suggested as potential factors underlying interindividual variability in risk taking and in brain activation during the processing of feedback. Here, we studied the effects of dopaminergic (dopamine transporter [DAT1], catecholamine-O-methyltransferase val158met [COMT]) and serotonergic (serotonin transporter [5HTTLPR]) polymorphisms on risk taking and brain responses following feedback in 60 healthy female subjects. The subjects completed a well-established experimental gambling paradigm while an electroencephalogram was recorded. During the task, risk-taking behavior and prefrontal brain responses (feedback-related negativity [FRN]) following monetary gains and losses were assessed. FRN amplitudes were enhanced for nine-repeat-allele carriers of the DAT1 and short-allele carriers of 5HTTLPR, which are both presumably linked to less transporter activity and higher neurotransmitter levels. Moreover, nine-repeat DAT1 carriers displayed a trend toward increased risk taking in general, whereas 5HTTLPR short-allele carriers showed decreased risk taking following gains. COMT val158met genotype was unrelated to FRN amplitude and average risk taking. However, COMT met/met carriers showed a pronounced feedback P3 amplitude independent of valence, and a gradual increase in risk taking during the gambling task. In sum, the present findings underline the importance of genetic variability in the dopamine and serotonin systems regarding the neurophysiology of feedback processing.
Cognitive Affective & Behavioral Neuroscience 07/2012; · 3.57 Impact Factor
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ABSTRACT: Feedback-related negativity (FRN) is associated with reinforcement learning and punishment sensitivity. Furthermore, reinforcement learning proficiency can be predicted from pre-task baseline EEG theta/beta ratio. In this study it was examined whether there was a relation between baseline theta/beta ratio in rest and FRN amplitude during a gambling task, and if such a correlation would be related to theta activity or to beta activity.
Baseline EEG and a self-report measure of punishment sensitivity (BIS) were obtained from 52 healthy volunteers. FRN was recorded during a gambling task.
FRN amplitude was negatively correlated with theta/beta ratio in high BIS individuals. Furthermore, source localization indicated that baseline theta activity generated in the anterior cingulate cortex (ACC) accounted for this correlation. For low BIS individuals no correlation was found.
An association between high baseline theta/beta ratio with low amplitude FRN and high risk-taking can be found in individuals who score sufficiently high on the BIS scale. This relationship is carried mostly by baseline theta activity, but not by beta activity.
This link between baseline brain activity, self-report measures and feedback processing may contribute to further understanding the biological basis of conditions that are accompanied by abnormal theta/beta ratio and reward processing, such as attention deficit hyper activity disorder (ADHD).
Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology 04/2012; 123(10):1958-65. · 3.12 Impact Factor
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ABSTRACT: Decreases in GH secretion with age may contribute to cognitive changes associated with aging. We evaluated the relation between GH secretion and cognition in elderly males by assessing correlations between GH secretion and performance on cognitive tests in conjunction with recording of event-related potentials (ERPs) to assess underlying neurophysiological mechanisms. GH secretion of 17 elderly male participants was assessed by a GHRH-GHRP-6 test. Standardized neuropsychological tests were used to assess cognitive function. EEG/ERPs were recorded to assess on-line electrocortical correlates of sensory-cortical processing and selective attention. GH secretion was significantly correlated with target detections and speed of responding in the selection-potential task. Furthermore, GH peak was significantly correlated with the performance letter-digit span test. The present data confirm that cognitive performance in elderly males is associated with GH secretion, with respect to target detection and speed of responding in conditions of selective attention, short-term memory, and basic processing speed.
Neurobiology of aging 03/2012; 33(3):582-7. · 5.94 Impact Factor
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ABSTRACT: The objective of this study was to investigate the relation between growth hormone (GH) and attentional electro-cortical responses to task-relevant stimuli (N2b), target detections, speed of responding, P300 latencies, and performance on neuropsychological tests in 19 patients who received external beam radiation therapy for brain tumors in adulthood. In addition, we studied the association between IGF-I and activation of the motor cortex responses (lateralized readiness potential, LRP). Brain function was assessed using event-related potentials (ERPs) during a go/no go selective-attention task, including N2b, P300 and selective motor preparation as reflected in the LRP. Correlations were calculated between peak GH levels after a standardized growth hormone-releasing hormone (GHRH)-arginine test, plasma IGF-I, and cognitive functions. We separately studied four patients who were diagnosed with GHD according to the GHRH-arginine test. Performance on WAIS digit span backward and the Rey-Osterrieth complex figure test correlated positively with GH peak. GHD patients performed worse than non-GHD patients on Stroop interference, trail making B/A attentional shifting and Rey-Osterrieth complex figure test. At trend-level significance, trails A performance was better in patients with lower GH levels and higher radiation doses, and GHD participants detected fewer targets in the go/no go selective attention task. N2b was not significantly altered by GH status. Furthermore, plasma IGF-I was positively correlated with the sum of digit span forward and backward. No relations with P300 were observed. In this study only 21% (4/19) of the patients who received fractionated radiotherapy for a non-endocrine brain tumor were diagnosed with GHD. GHD in these patients was associated with impaired interference control, attentional shifting, and visual long-term memory. The results for interference control and attentional shifting suggest an additional effect of the radiation history.
Growth hormone & IGF research: official journal of the Growth Hormone Research Society and the International IGF Research Society 02/2012; 22(1):42-7. · 2.35 Impact Factor
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ABSTRACT: Objective: Cannabis intake has been reported to affect cognitive functions such as selective attention. This study addressed the effects of exposure to cannabis with up to 69.4mg Delta(9)-tetrahydrocannabinol (THC) on Event-Related Potentials (ERPs) recorded during a visual selective attention task. Methods: Twenty-four participants smoked cannabis cigarettes with four doses of THC on four test days in a randomized, double blind, placebo-controlled, crossover study. Two hours after THC exposure the participants performed a visual selective attention task and concomitant ERPs were recorded. Results: Accuracy decreased linearly and reaction times increased linearly with THC dose. However, performance measures and most of the ERP components related specifically to selective attention did not show significant dose effects. Only in relatively light cannabis users the Occipital Selection Negativity decreased linearly with dose. Furthermore, ERP components reflecting perceptual processing, as well as the P300 component, decreased in amplitude after THC exposure. Only the former effect showed a linear dose-response relation. Conclusions: The decrements in performance and ERP amplitudes induced by exposure to cannabis with high THC content resulted from a non-selective decrease in attentional or processing resources. Significance: Performance requiring attentional resources, such as vehicle control, may be compromised several hours after smoking cannabis cigarettes containing high doses of THC, as presently available in Europe and Northern America.
Pharmacology Biochemistry and Behavior 07/2010; 96(1):67-74. · 2.53 Impact Factor
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Psychopharmacologia 04/2010; · 4.08 Impact Factor
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ABSTRACT: Background and Aim: External beam radiation therapy on the brain can lead to growth hormone
deficiency (GHD) by damaging the pituitary. Reduced concentrations of growth hormone (GH)
and circulating insulin-like growth factor-I (IGF-I) are both found to be associated with
deteriorated cognitive performance. The objective of this study was to assess in patients with or
without GHD after radiation therapy on the brain, the effect on cognition and the distinctive roles
of GH and IGF-I.
Subjects and Methods: We recruited 21 patients (8 females, age 32-62, males age 30-62), who
received external beam radiation therapy for brain tumors. Four GHD (mean age 46, range 36-
57; 1 female of 57) patients were compared to 16 non-GHD patients. GHD was diagnosed using
the standard Arginine-GHRH test. Plasma IGF-I was assessed at baseline. Cognitive functions
were assessed by standardized neuropsychological tests. ERPs were recorded during a go/ no
go selective attention task.
Results: In the selective attention task, GHD subjects detected fewer targets (trend-level effect)
and had smaller N2bs on average. GHD subjects performed worse compared to non-GHD
patients on critical measures of the Stroop interference, trail making B/A attentional shifting and
Rey-Osterrieth complex figure test. IGF-I levels did not differ between GHD and non-GHD
subjects. No correlation was observed between plasma IGF-I and GH peak response to Arginine-
GHRH in both groups.
Conclusion: Patients with GHD after external beam brain radiation have impaired cognitive
functioning in certain domains, i.e. interference control, attentional shifting, and visual & nonverbal
memory. As no association was observed between these cognitive measures and IGF-I,
we suggest that in subjects with GHD after external beam radiation on the brain impairment of
the GH/IGF-I axis is limited to GH secretory capacity.
ENP 2009; 06/2009
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ABSTRACT: The acquisition of a conditioned fear response is adaptive, as it enables the organism to appropriately respond to predictors of aversive events. Consequently, the absence of predictive cues can be used as a signal for safety. We aimed to study whether deficient fear conditioning might lead to maladaptive fear. Following previous work, we predicted that failure to learn the CS-US association would result in higher contextual fear, and that participants who failed to learn would tend to exhibit higher trait anxiety. Conditioning took place in a virtual environment with two contexts. In one of the two contexts, offset of a CS (light) was associated with a shock. Each participant visited two places (a house and an apartment) in each of 12 blocks. In one of these places shocks were administered at the offset of an 8-s period of lights on (CS). The results showed that half of the participants demonstrated differential shock expectancy between situations in the shock context in which the CS was present versus absent. This indicates that these participants learned the contingencies between the shocks and both the context and the light CS. In contrast, the other half of the participants learned only the association with the context. As predicted, learning the CS-US contingency resulted in reduced self-reported fear in the absence of the CS in the danger context compared to the presence of the CS. On the other hand, participants who failed to learn the association displayed a sustained aversive state throughout the duration of the danger context. Skin conductance measures confirmed this pattern of results. Fear-potentiated startle during the threat context compared to the safe context was significant in both groups, while startle was only potentiated during the CS in the threat context in the group that learned the CS association (trend-level significant). Finally, scores on Spielberger's self-report scale of trait anxiety tended to be higher in the group of participants who did not learn the CS-shock association in the danger context compared to participants who did. In conclusion, these results confirm higher contextual fear in participants who did not acquire a conditioned response to the cue in comparison to participants who did. Also, virtual reality contexts provide a useful tool for the study of context conditioning.
Acta Psychologica 04/2008; 127(3):581-92. · 2.26 Impact Factor
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ABSTRACT: Inattention and distraction account for a substantial number of traffic accidents. Therefore, we examined the impact of secondary task performance (an auditory oddball task) on a primary driving task (lane keeping). Twenty healthy participants performed two 20-min tests in the Divided Attention Steering Simulator (DASS). The visual secondary task of the DASS was replaced by an auditory oddball task to allow recording of brain activity. The driving task and the secondary (distracting) oddball task were presented in isolation and simultaneously, to assess their mutual interference. In addition to performance measures (lane keeping in the primary driving task and reaction speed in the secondary oddball task), brain activity, i.e. event-related potentials (ERPs), was recorded. Performance parameters on the driving test and the secondary oddball task did not differ between performance in isolation and simultaneous performance. However, when both tasks were performed simultaneously, reaction time variability increased in the secondary oddball task. Analysis of brain activity indicated that ERP amplitude (P3a amplitude) related to the secondary task, was significantly reduced when the task was performed simultaneously with the driving test. This study shows that when performing a simple secondary task during driving, performance of the driving task and this secondary task are both unaffected. However, analysis of brain activity shows reduced cortical processing of irrelevant, potentially distracting stimuli from the secondary task during driving.
Accident Analysis & Prevention 02/2008; 40(1):1-7. · 1.87 Impact Factor
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ABSTRACT: While preparing a saccadic eye movement, visual processing of the saccade goal is prioritized. Here, we provide evidence that the frontal eye fields (FEFs) are responsible for this coupling between eye movements and shifts of visuospatial attention. Functional magnetic resonance imaging (fMRI)-guided transcranial magnetic stimulation (TMS) was applied to the FEFs 30 ms before a discrimination target was presented at or next to the target of a saccade in preparation. Results showed that the well-known enhancement of discrimination performance on locations to which eye movements are being prepared was diminished by TMS contralateral to eye movement direction. Based on the present and other reports, we propose that saccade preparatory processes in the FEF affect selective visual processing within the visual cortex through feedback projections, in that way coupling saccade preparation and visuospatial attention.
Journal of Neurophysiology 12/2007; 98(5):2765-78. · 3.32 Impact Factor
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ABSTRACT: A central question in the study of selective attention is whether top-down attentional control mechanisms are generalized or specialized for the type of information that is to be attended. The current study examined this question using a voluntary orienting task that cued observers to attend to either one of two locations or to one of two colors. Location (spatial) and color (nonspatial) conditions were presented either randomly intermixed within the same block of trials or in separate blocks. Functional magnetic resonance imaging revealed that directing attention to a location or to a color activated a network of overlapping dorsal frontal and parietal areas, previously implicated in attentional control. The pattern of observed overlap was not affected by the intermixed versus blocked presentation of location and color conditions. Although portions of the frontal-parietal network were more active in response to location cues than to color cues, a secondary analysis also revealed that medial dorsal frontal and parietal cortex were specifically engaged in shifting visual attention regardless of the cued dimension (location or color). Together, the present results support the conclusion that attentional control is the combination of a generalized network that works in concert with subregions of the frontoparietal network that are highly specialized for directing attention based on the content of the to-be-attended information.
Brain Research 11/2007; 1177:90-102. · 2.73 Impact Factor
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ABSTRACT: Basic abnormalities in visual information processing could be associated with the local visual bias often found in subjects with PDD. Therefore, the present study investigated the existence of deficits in spatial frequency processing at an early sensory level in children with PDD.
Visual evoked potentials (VEPs) and VEP dipole sources elicited by high and low spatial frequency gratings were analyzed in high-functioning children with PDD and matched controls.
Around 80 ms (N80-latency) children with PDD did not show the same robust differences between high and low spatial frequencies in VEP amplitude and VEP brain sources as controls, because of atypical processing of high frequencies. Analyses at the P1-latency (130 ms) revealed that, although similar inferior-medial brain sources were activated for the processing of both spatial frequencies in the PDD and control group, source strength in response to both frequencies was weaker in the PDD compared to control group. Moreover, additional superior-lateral brain sources were activated during the processing of both frequencies in the PDD group.
Decreased specialized processing of high and low spatial frequencies might be a robust characteristic of PDD. Early in processing abnormalities in high spatial frequency processing seem to occur in PDD. At a later phase in processing there seems to be both atypical high and low spatial frequency processing. Considering that the processing of specific spatial frequencies plays an important role in the processing of global and local aspects of hierarchical stimuli and faces and of emotions, present data suggest that peculiarities in PDD subjects with respect to these stimuli might be related to an abnormality in more fundamental visual processes.
A basic abnormality in visual frequency processing is established in children with PDD.
Clinical Neurophysiology 10/2007; 118(9):2076-88. · 3.41 Impact Factor
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ABSTRACT: Both a reduced face expertise and a basic abnormality in visual information, e.g. spatial frequency, processing have been proposed as possible causes of the abnormal face processing in Pervasive Developmental Disorder (PDD). This study investigated both the roles of expertise and spatial frequency for face processing in PDD. Event-related potentials (ERPs) and dipole sources were measured in response to (upright/inverted) high- and low-pass filtered faces, houses, and stimuli for which children with PDD were experts. ERP analyses for specific posterior electrodes showed no differences between children with PDD and matched controls, but source analyses did. These showed that controls activated specialized brain sources for the processing of faces, which was dependent on low spatial frequency content. However, children with PDD did not. Importantly, present results argue against the idea that this is due to a reduced face expertise on the part of the children with PDD, but instead support an abnormality in spatial frequency processing.
Acta Neurovegetativa 02/2007; 114(12):1619-29. · 2.73 Impact Factor
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ABSTRACT: The attitudes of patients towards driving a car while taking medication with psychotropic side effects is unclear. A growing number of patients use these psychotropic medicines on a daily basis, and this may interfere with their ability to drive a car.
By means of a survey, we examined attitudes towards driving while using psychotropic medicinal drugs and the effect of warning labels on the decision whether to drive a car or not in patients with chronic pain.
Fifty-eight of 100 patients possessing a driver's license used psychotropic medication. Despite warning labels affixed on the packages that these drugs might impair driving ability, the majority (71%) of these patients continued driving a car. A point of concern is that 40% of these patients reported not to be more cautious in traffic after taking psychotropic drugs.
The results of this survey indicate that drug warning labels applied by Dutch pharmacies do not significantly change attitudes towards driving a car in patients taking medicinal drugs with psychotropic side effects. Future road-safety campaigns should pay more attention to the impairing effects of psychotropic drugs on driving.
Traffic Injury Prevention 01/2007; 7(4):360-4. · 1.08 Impact Factor
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ABSTRACT: An ongoing controversy concerns whether executive control mechanisms can actively reconfigure the cognitive system in preparation for switching to a new task set. To address this question, we recorded brain activity from 14 healthy participants, using event-related functional magnetic resonance imaging, while they performed a cued attention task. Critically, in any particular trial, the cued task set was either the same as that in the previous trial or switched. As was hypothesized, cue-related, switch-specific preparatory activity was observed in a network of dorsal frontal and parietal brain areas that are typically associated with cognitive control processes. Moreover, the magnitude of switch-specific preparatory activity varied with the number of possible task sets that could be presented in a given trial block. These findings provide compelling support for the existence of top-down, preparatory control processes that enable set switching. Furthermore, they demonstrate that global task structure is a critical determinant of whether switch-specific preparatory activity is observed.
Cognitive Affective & Behavioral Neuroscience 10/2006; 6(3):175-89. · 3.57 Impact Factor
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ABSTRACT: Most pain patients are treated in an outpatient setting and are engaged in daily activities including driving. Since several studies showed that cognitive functioning may be impaired in chronic nonmalignant pain, the question arises whether or not chronic nonmalignant pain affects driving performance. Therefore, the objective of the present study was to determine the effects of chronic nonmalignant pain on actual highway driving performance during normal traffic. Fourteen patients with chronic nonmalignant pain and 14 healthy controls, matched on age, educational level, and driving experience, participated in the study. Participants performed a standardized on-the-road driving test during normal traffic, on a primary highway. The primary parameter of the driving test is the Standard Deviation of Lateral Position (SDLP). In addition, driving-related skills (tracking, divided attention, and memory) were examined in the laboratory. Subjective assessments, such as pain intensity, and subjective driving quality, were rated on visual analogue scales. The results demonstrated that a subset of chronic nonmalignant pain patients had SDLPs that were higher than the matched healthy controls, indicating worse highway driving performance. Overall, there was a statistically significant difference in highway driving performance between the groups. Further, chronic nonmalignant pain patients rated their subjective driving quality to be normal, although their ratings were significantly lower than those of the healthy controls. No significant effects were found on the laboratory tests.
Pain 06/2006; 122(1-2):28-35. · 5.78 Impact Factor
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ABSTRACT: Chronic pain may impair performance on attentional processing capacity tasks. In the present study, event-related potentials were recorded to examine whether pain patients show performance decrements on attentional processing capacity tasks due to shared resources by pain and attention or, alternatively, due to deficits in allocating attentional resources during pain. Fourteen chronic pain patients and thirty age and education matched healthy controls were investigated. An attentional capacity probe task was used in which the difficulty level was manipulated, resulting in an easy and a difficult condition, while task-irrelevant visual probes were presented. These probe-elicited P3 amplitudes were assumed to provide the most pure estimate of processing capacity since they are relatively free from target-related processes. Event-related potentials were recorded from the midline electrodes Fz, Cz, Pz, and Oz. For the behavioral measures, it was found that pain patients maintained a different speed-accuracy tradeoff. Pain patients showed faster reaction time responses and higher error rates compared to controls. No significant differences were found between pain patients and controls on the primary task. Pain patients differed from controls with respect to amplitudes elicited by task-irrelevant probe stimuli. For healthy controls, the expected decreased amplitude was found for probe stimuli in the difficult compared to the easy task. In contrast, the pain patients did not show decreased probe amplitudes with increasing task load. The data may imply that allocation of attentional resources is deficient in pain patients, instead of attentional capacity.
Pain 04/2006; 121(1-2):60-8. · 5.78 Impact Factor
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ABSTRACT: Little is known about the effects of low doses of amitriptyline, prescribed in the treatment of neuropathic pain, on attentional processing capacity.
Changes due to amitriptyline treatment on attentional processing capacity were investigated on behavioral measures and event-related brain potentials (ERPs) in six patients with neuropathic pain.
Patients were treated for 15 consecutive days with 25 mg nocturnally administered amitriptyline or placebo in a double-blind crossover randomized design. Measurements were carried out on day 1 and day 15 of each treatment period. An attentional capacity probe task was used in which the difficulty level was manipulated, resulting in an easy and a hard condition, while task-irrelevant visual probes were presented. During task performance, ERPs were measured from the midline electrodes Fz, Cz, Pz, and Oz.
Amitriptyline increased reaction times (RTs) after acute but not after subchronic administration. ERP analyses showed that P3 amplitudes to the task stimuli were not affected by amitriptyline in either treatment phase. Moreover, P3 amplitudes to the probes were increased in the easy compared to the hard task condition after subchronic amitriptyline treatment, indicating beneficial effects of repeated amitriptyline administration. In contrast, acute amitriptyline administration did reduce an earlier visual evoked potential, N1, preceding the P3 component.
The results suggest that amitriptyline, even at low dosages of 25 mg, affects performance after acute administration in chronic neuropathic pain patients. After 2 weeks of treatment, performance appears to be unaffected. No deficits in processing capacity due to amitriptyline treatment were found.
Psychopharmacologia 02/2006; 183(4):462-70. · 4.08 Impact Factor
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ABSTRACT: Smoking is highly prevalent among patients with Attention Deficit Hyperactivity Disorder (ADHD). Previous studies using the reversed continuous performance task (R-CPT) have suggested that nicotine reduces inattention. Since especially adults with ADHD have been claimed to suffer from a core deficit in inhibitory control, this study aimed at determining whether nicotine improves response inhibition in addition to attention. Sixteen healthy regular smokers participated in a pre/post treatment design in which transdermal patches containing 7 and 21 mg nicotine per day were administered in a counterbalanced, double-blind manner. In a second study, patches containing 0 mg (placebo) and 21 mg per day were administered to a different group of regular smokers. For replication purposes, the R-CPT and the profile of mood states (POMS) were administered. Furthermore, a different version of the continuous performance task (CPT-AX) and the stop-signal task, traditionally used to measure response inhibition, were presented. The high dose of nicotine was found to relieve self-reported Depression in Study 1 and Fatigue in Study 2. Performance data indicated acute effects of nicotine on attention-related, but not on inhibition-related measures. Especially the comparison with placebo revealed decreases in reaction time and variability of responding. The results imply that patients with ADHD smoke to reduce inattention.
Pharmacology Biochemistry and Behavior 12/2005; 82(3):539-48. · 2.53 Impact Factor
