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1.
Int J Psychophysiol ; 193: 112239, 2023 11.
Article in English | MEDLINE | ID: mdl-37643661

ABSTRACT

Impulse control and adequate decision making are vital functions when it comes to detection and adherence to personal goals and societal rules. In the current study we tested the hypothesis that increasing the salience of environmental cues would be most effective in improving impulse control, as assessed by a stop-signal task, in subjects with low environmental susceptibility as indexed by low pre-stimulus EEG alpha power. In addition, we anticipated that an external-reward manipulation improves performance during a Go/No go task, especially in individuals with low task-induced motivation as indexed by low theta/beta power ratios. High salience of stop signals enhanced stopping performance but there was no difference in responsivity to the salience manipulation between participants with high and low EEG alpha power. Individuals with low theta/beta power ratios responded more accurately when rewards were involved. Together these results suggest that increasing the salience of external cues may help impulse control in general, whereas the effectiveness of external-reward manipulations is higher in individuals with low task-induced motivation.


Subject(s)
Motivation , Self-Control , Humans , Individuality , Reward , Cues
2.
Front Neurosci ; 16: 1078586, 2022.
Article in English | MEDLINE | ID: mdl-36685234

ABSTRACT

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder characterized by social impairments and restricted, repetitive behaviors. Treatment of ASD is notoriously difficult and might benefit from identification of underlying mechanisms that overlap with those disturbed in other developmental disorders, for which treatment options are more obvious. One example of the latter is attention-deficit hyperactivity disorder (ADHD), given the efficacy of especially stimulants in treatment of ADHD. Deficiencies in catecholaminergic systems [dopamine (DA), norepinephrine (NE)] in ADHD are obvious targets for stimulant treatment. Recent findings suggest that dysfunction in catecholaminergic systems may also be a factor in at least a subgroup of ASD. In this review we scrutinize the evidence for catecholaminergic mechanisms underlying ASD symptoms, and also include in this analysis a third classic ascending arousing system, the acetylcholinergic (ACh) network. We complement this with a comprehensive review of DA-, NE-, and ACh-targeted interventions in ASD, and an exploratory search for potential treatment-response predictors (biomarkers) in ASD, genetically or otherwise. Based on this review and analysis we propose that (1) stimulant treatment may be a viable option for an ASD subcategory, possibly defined by genetic subtyping; (2) cerebellar dysfunction is pronounced for a relatively small ADHD subgroup but much more common in ASD and in both cases may point toward NE- or ACh-directed intervention; (3) deficiency of the cortical salience network is sizable in subgroups of both disorders, and biomarkers such as eye blink rate and pupillometric data may predict the efficacy of targeting this underlying deficiency via DA, NE, or ACh in both ASD and ADHD.

3.
Sci Rep ; 11(1): 8287, 2021 04 15.
Article in English | MEDLINE | ID: mdl-33859332

ABSTRACT

Emotional facial expressions are important visual communication signals that indicate a sender's intent and emotional state to an observer. As such, it is not surprising that reactions to different expressions are thought to be automatic and independent of awareness. What is surprising, is that studies show inconsistent results concerning such automatic reactions, particularly when using different face stimuli. We argue that automatic reactions to facial expressions can be better explained, and better understood, in terms of quantitative descriptions of their low-level image features rather than in terms of the emotional content (e.g. angry) of the expressions. Here, we focused on overall spatial frequency (SF) and localized Histograms of Oriented Gradients (HOG) features. We used machine learning classification to reveal the SF and HOG features that are sufficient for classification of the initial eye movement towards one out of two simultaneously presented faces. Interestingly, the identified features serve as better predictors than the emotional content of the expressions. We therefore propose that our modelling approach can further specify which visual features drive these and other behavioural effects related to emotional expressions, which can help solve the inconsistencies found in this line of research.


Subject(s)
Emotions/physiology , Eye Movements/physiology , Face/pathology , Facial Expression , Adult , Female , Humans , Machine Learning , Male , Photic Stimulation , Young Adult
4.
Eur Child Adolesc Psychiatry ; 24(1): 105-13, 2015 Jan.
Article in English | MEDLINE | ID: mdl-24643447

ABSTRACT

Empathy has been associated with decreased antisocial and increased prosocial behavior. This study examined empathy and prosocial behavior in response to sadness and distress in disruptive behavior disorder (DBD) and attention-deficit hyperactivity disorder (ADHD). Six- and 7-year-old children with DBD (with and without ADHD) (n = 67) and with ADHD only (n = 27) were compared to typically developing children (TD) (n = 37). Parents and teachers rated affective empathy in response to sadness and distress on the Griffith Empathy Measure. Children reported affective empathic ability in response to sad story vignettes. Empathy-induced prosocial behavior in response to sadness and distress was assessed with a computer task, the Interpersonal Response Task (IRT). Compared to TD, children with DBD (with and without ADHD) and those with ADHD only were rated as less empathic by their teachers, but not by their parents. No differences between groups were observed in children who reported affect correspondence. Children with DBD (with and without ADHD) showed less prosocial behavior in response to sadness and distress compared to TD. Children with ADHD only did not differ from TD. An additional analysis comparing all children with a diagnosis to the TD group revealed that the difference in prosocial behavior remained after controlling for ADHD symptoms, but not after controlling for DBD symptoms. These findings of impaired empathy-induced prosocial behavior in response to sadness and distress in young children with DBD suggest that interventions to ameliorate peer relationships may benefit from targeting on increasing prosocial behavior in these children.


Subject(s)
Attention Deficit Disorder with Hyperactivity/psychology , Attention Deficit and Disruptive Behavior Disorders/psychology , Emotions , Empathy , Social Behavior , Attention Deficit Disorder with Hyperactivity/diagnosis , Attention Deficit and Disruptive Behavior Disorders/diagnosis , Case-Control Studies , Child , Female , Humans , Male
5.
J Autism Dev Disord ; 45(2): 354-62, 2015 Feb.
Article in English | MEDLINE | ID: mdl-23888357

ABSTRACT

This study aimed to examine facial mimicry in 6-7 year old children with autism spectrum disorder (ASD) and to explore whether facial mimicry was related to the severity of impairment in social responsiveness. Facial electromyographic activity in response to angry, fearful, sad and happy facial expressions was recorded in twenty 6-7 year old children with ASD and twenty-seven typically developing children. Even though results did not show differences in facial mimicry between children with ASD and typically developing children, impairment in social responsiveness was significantly associated with reduced fear mimicry in children with ASD. These findings demonstrate normal mimicry in children with ASD as compared to healthy controls, but that in children with ASD the degree of impairments in social responsiveness may be associated with reduced sensitivity to distress signals.


Subject(s)
Child Development Disorders, Pervasive/physiopathology , Child Development Disorders, Pervasive/psychology , Emotions/physiology , Face/physiology , Facial Expression , Imitative Behavior/physiology , Case-Control Studies , Child , Electromyography , Female , Humans , Male , Social Skills
6.
Behav Brain Res ; 274: 344-8, 2014 Nov 01.
Article in English | MEDLINE | ID: mdl-25116250

ABSTRACT

It has long been postulated that exogenous cannabinoids have a profound effect on human cognitive functioning. These cannabinoid effects are thought to depend, at least in parts, on alterations of phase-locking of local field potential neuronal firing. The latter can be measured as activity in the theta frequency band (4-7Hz) by electroencephalogram. Theta oscillations are supposed to serve as a mechanism in neural representations of behaviorally relevant information. However, it remains unknown whether variability in endogenous cannabinoid activity is involved in theta rhythms and therefore, may serve as an individual differences index of human cognitive functioning. To clarify this issue, we recorded resting state EEG activity in 164 healthy human subjects and extracted EEG power across frequency bands (δ, θ, α, and ß). To assess variability in the endocannabinoid system, two genetic polymorphisms (rs1049353, rs2180619) within the cannabinoid receptor 1 (CB1) were determined in all participants. As expected, we observed significant effects of rs1049353 on EEG power in the theta band at frontal, central and parietal electrode regions. Crucially, these effects were specific for the theta band, with no effects on activity in the other frequency bands. Rs2180619 showed no significant associations with theta power after Bonferroni correction. Taken together, we provide novel evidence in humans showing that genetic variability in the cannabinoid receptor 1 is associated with resting state EEG power in the theta frequency band. This extends prior findings of exogenous cannabinoid effects on theta power to the endogenous cannabinoid system.


Subject(s)
Brain/physiology , Polymorphism, Single Nucleotide/genetics , Receptor, Cannabinoid, CB1/genetics , Rest , Theta Rhythm/genetics , Adult , Electroencephalography , Female , Genetic Linkage , Humans , Male , Young Adult
7.
Neuroscience ; 277: 375-82, 2014 Sep 26.
Article in English | MEDLINE | ID: mdl-25050819

ABSTRACT

The cholinergic system is implicated in visuospatial attention and inhibition, however the exact role is still unclear. Two key mechanisms in visuospatial attention are bias and disengagement. Bias refers to neuronal signals that enhance the sensitivity of the sensory cortex, disengagement is the decoupling of attention. Previous studies suggest that nicotine affects disengagement and (related) inhibition. However the exact relation is still unknown. Furthermore, nicotine-abstinence in 'healthy' smokers may resemble some anomalies of visuospatial attention and inhibition as seen in Attention Deficit/Hyperactivity Disorder (ADHD). Smokers and non-smokers (32 male students) performed in a visuospatial cueing (VSC) task, to assess bias and disengagement, and in a stop-signal task (SST) to assess inhibition. It was expected that nicotine abstinent smokers compared to non-smokers, would show poor disengagement (indicated by an enhanced validity effect) and poor inhibitory control (indicated by an enhanced stop-signal reaction time (SSRT)). It was expected that nicotine would positively affect disengagement and inhibition: hypothesis 1 stated that this effect would be larger in smokers as opposed to non-smokers, in terms of smoking-related deficient inhibitory control. Hypothesis 2 stated the exact opposite, in terms of drug-tolerance. Results indicated no baseline differences. Nicotine enhanced inhibition more in non-smokers relative to smokers. Integrating the results, nicotine-abstinent smokers do not seem to resemble ADHD patients, and do not seem to smoke in order to self-medicate a pre-existing deficit pertaining to mechanisms of visuospatial attention and inhibition. Nicotine may affect inhibition more in non-smokers relative to smokers, consistent with a drug-tolerance account.


Subject(s)
Attention/drug effects , Inhibition, Psychological , Nicotine/pharmacology , Nicotinic Agonists/pharmacology , Smoking/physiopathology , Visual Perception/drug effects , Adolescent , Adult , Attention/physiology , Blood Pressure/drug effects , Blood Pressure/physiology , Cues , Heart Rate/drug effects , Heart Rate/physiology , Humans , Male , Neuropsychological Tests , Photic Stimulation , Psychomotor Performance/drug effects , Psychomotor Performance/physiology , Reaction Time/drug effects , Reaction Time/physiology , Single-Blind Method , Visual Perception/physiology , Young Adult
8.
Pharmacol Biochem Behav ; 122: 89-96, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24690513

ABSTRACT

The role of the cholinergic system in inhibition remains to be elucidated. Nicotine is a potent tool to augment this system, but most studies investigated its effects solely on behavior. Reference to brain activity is important to specifically identify inhibition-related mechanisms. In the current study the objective was to elucidate the role of the cholinergic system in inhibition. 16 healthy non-smokers performed in a stop task while EEG was recorded. A pre- versus post-treatment, within subjects, placebo controlled, single-blind design was used. It was hypothesized that nicotine would decrease stop-signal reaction time (SSRT) and increase the amplitude of inhibition-related event related potentials, the stop N2 and stop P3. Behavioral measures show nicotine shortened SSRT, but only when pretreatment values were not taken into account. On EEG measures, an enhanced stop P3 under nicotine was found, but only in a subsample sensitive to nicotine based on diastolic blood pressure. The results are indicative of enhanced inhibitory activity possibly reflecting enhanced activation in the superior frontal gyrus.


Subject(s)
Brain/drug effects , Cholinergic Neurons/drug effects , Electroencephalography/drug effects , Neural Inhibition/drug effects , Nicotine/administration & dosage , Synaptic Transmission/drug effects , Adolescent , Adult , Brain/physiology , Cholinergic Neurons/physiology , Electroencephalography/methods , Humans , Male , Neural Inhibition/physiology , Photic Stimulation/methods , Synaptic Transmission/physiology , Young Adult
9.
Behav Brain Res ; 260: 67-73, 2014 Mar 01.
Article in English | MEDLINE | ID: mdl-24316088

ABSTRACT

The cholinergic system has been implicated in visuospatial attention but the exact role remains unclear. In visuospatial attention, bias refers to neuronal signals that modulate the sensitivity of sensory cortex, while disengagement refers to the decoupling of attention making reorienting possible. In the current study we investigated the effect of facilitating cholinergic neurotransmission by nicotine (Nicorette Freshmint 2mg, polacrilex chewing gum) on behavioral and electrophysiological indices of bias and disengagement. Sixteen non-smoking participants performed in a Visual Spatial Cueing (VSC) task while EEG was recorded. A randomized, single-blind, crossover design was implemented. Based on the scarce literature, it was expected that nicotine would specifically augment disengagement related processing, especially manifest as an increase of the modulation of the Late Positive Deflection (LPD) by validity of cueing. No effect was expected on bias related components (cue-locked: EDAN, LDAP; target-locked: P1 and N1 modulations). Results show weak indications for a reduction of the reaction time validity effect by nicotine, but only for half of the sample in which the validity effect on the pretest was largest. Nicotine reduced the result of bias as indexed by a reduced P1 modulation by validity, especially in subjects with strong peripheral responses to nicotine. Nicotine did not affect ERP manifestations of the directing of bias (EDAN, LDAP) or disengagement (LPD).


Subject(s)
Attention/drug effects , Brain/drug effects , Cholinergic Agents/pharmacology , Space Perception/drug effects , Visual Perception/drug effects , Adolescent , Adult , Attention/physiology , Brain/physiology , Cross-Over Studies , Cues , Electroencephalography , Evoked Potentials , Hemodynamics/drug effects , Humans , Male , Nicotine/pharmacology , Random Allocation , Reaction Time/drug effects , Single-Blind Method , Space Perception/physiology , Synaptic Transmission/drug effects , Visual Perception/physiology , Young Adult
10.
J Clin Neurophysiol ; 30(3): 261-7, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23733090

ABSTRACT

Major depressive disorder has a large impact on patients and society and is projected to be the second greatest global burden of disease by 2020. The brain-derived neurotrophic factor (BDNF) gene is considered to be one of the important factors in the etiology of major depressive disorder. In a recent study, alpha power was found to mediate between BDNF Met and subclinical depressed mood. The current study looked at a population of patients with major depressive disorder (N = 107) to examine the association between the BDNF Val66Met polymorphism, resting state EEG alpha power, and depression severity. For this purpose, repeated-measures analysis of variance, partial correlation, and multiple linear models were used. Results indicated a negative association between parietal-occipital alpha power in the eyes open resting state and depression severity. In addition, Met/Met patients showed lower global absolute alpha power in the eyes closed condition compared with Val-carriers. These findings are in accordance with the previously uncovered pathway between BDNF Val66Met, resting state EEG alpha power, and depression severity. Additional research is needed for the clarification of this tentative pathway and its implication in personalized treatment of major depressive disorder.


Subject(s)
Alpha Rhythm , Brain-Derived Neurotrophic Factor/genetics , Depression/diagnosis , Depression/genetics , Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/genetics , Severity of Illness Index , Adult , Depression/epidemiology , Depressive Disorder, Major/epidemiology , Female , Genetic Predisposition to Disease/epidemiology , Genetic Predisposition to Disease/genetics , Humans , Male , Netherlands/epidemiology , Prevalence , Reproducibility of Results , Risk Factors , Sensitivity and Specificity
11.
Behav Brain Res ; 249: 55-64, 2013 Jul 15.
Article in English | MEDLINE | ID: mdl-23619133

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).


Subject(s)
Catechol O-Methyltransferase/genetics , Dopamine Plasma Membrane Transport Proteins/genetics , Event-Related Potentials, P300/genetics , Evoked Potentials, Auditory/genetics , Polymorphism, Single Nucleotide , Serotonin Plasma Membrane Transport Proteins/genetics , Alleles , Dopamine/genetics , Female , Genotype , Humans , Reaction Time/genetics , Serotonin/genetics , Young Adult
12.
J Neurophysiol ; 110(1): 33-41, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23596329

ABSTRACT

Perception of relevant visual object features can be modulated by the preparation of an action toward it ("action-modulated perception"). For instance, the perception of the orientation of a book can be enhanced when preparing to grasp it (but not when pointing to it). However, the underlying neuronal mechanisms are poorly understood. We argue that brain areas controlling arm movements are involved in establishing this effect through top-down feedback to early visual areas, similar to the neuronal mechanisms linking visual attention and eye movements. To investigate this involvement, we applied transcranial magnetic stimulation to a grasping motor area, the left anterior intraparietal sulcus (aIPS), during grasping or pointing preparation. Concurrently, an orientation change detection task was performed. As a control area, the vertex was stimulated. We found that stimulation of aIPS selectively modulates orientation sensitivity during action preparation compared with control stimulation (vertex), negating the increased orientation sensitivity with grasping preparation over pointing preparation. We argue that aIPS is a critical part of the mechanism underlying perceptual modulations during action preparation. The present results and recent literature suggest that this action-modulated perception for hand movements is implemented through a cortical feedback connection between aIPS and early visual areas.


Subject(s)
Movement/physiology , Parietal Lobe/physiology , Signal Detection, Psychological/physiology , Adult , Female , Humans , Male , Transcranial Magnetic Stimulation , Visual Perception
13.
Cogn Affect Behav Neurosci ; 12(4): 678-91, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22810728

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.


Subject(s)
Catechol O-Methyltransferase/genetics , Dopamine Plasma Membrane Transport Proteins/genetics , Evoked Potentials/genetics , Feedback, Psychological/physiology , Polymorphism, Genetic/genetics , Risk-Taking , Serotonin Plasma Membrane Transport Proteins/genetics , Adolescent , Analysis of Variance , Brain Mapping , Choice Behavior/physiology , Electroencephalography , Female , Games, Experimental , Humans , Reaction Time/genetics , Young Adult
14.
Int J Psychophysiol ; 85(2): 195-9, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22634269

ABSTRACT

Preliminary studies have demonstrated that school-aged children (average age 9-10years) show mimicry responses to happy and angry facial expressions. The aim of the present study was to assess the feasibility of using facial electromyography (EMG) as a method to study facial mimicry responses in younger children aged 6-7years to emotional facial expressions of other children. Facial EMG activity to the presentation of dynamic emotional faces was recorded from the corrugator, zygomaticus, frontalis and depressor muscle in sixty-one healthy participants aged 6-7years. Results showed that the presentation of angry faces was associated with corrugator activation and zygomaticus relaxation, happy faces with an increase in zygomaticus and a decrease in corrugator activation, fearful faces with frontalis activation, and sad faces with a combination of corrugator and frontalis activation. This study demonstrates the feasibility of measuring facial EMG response to emotional facial expressions in 6-7year old children.


Subject(s)
Aging , Electromyography , Emotions/physiology , Facial Expression , Facial Muscles/physiology , Analysis of Variance , Child , Feasibility Studies , Female , Humans , Male , Photic Stimulation , Predictive Value of Tests
15.
Clin Neurophysiol ; 123(10): 1958-65, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22542439

ABSTRACT

OBJECTIVE: 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. METHODS: Baseline EEG and a self-report measure of punishment sensitivity (BIS) were obtained from 52 healthy volunteers. FRN was recorded during a gambling task. RESULTS: 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. CONCLUSIONS: 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. SIGNIFICANCE: 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).


Subject(s)
Cerebral Cortex/physiology , Feedback, Psychological/physiology , Punishment , Reward , Risk-Taking , Adolescent , Adult , Brain Mapping , Electroencephalography , Female , Gambling/physiopathology , Gambling/psychology , Humans , Learning/physiology , Male , Self Report , Surveys and Questionnaires
16.
Growth Horm IGF Res ; 22(1): 42-7, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22269954

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.


Subject(s)
Cognition Disorders/psychology , Cranial Irradiation/adverse effects , Human Growth Hormone/metabolism , Radiation Injuries/psychology , Adult , Aged , Cognition Disorders/etiology , Female , Humans , Insulin-Like Growth Factor I/metabolism , Male , Middle Aged , Radiation Injuries/etiology
17.
Neurobiol Aging ; 33(3): 582-7, 2012 Mar.
Article in English | MEDLINE | ID: mdl-20483505

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.


Subject(s)
Aging/physiology , Cerebral Cortex/physiopathology , Cognition Disorders/physiopathology , Human Growth Hormone/metabolism , Aged , Cerebral Cortex/metabolism , Cognition Disorders/metabolism , Human Growth Hormone/deficiency , Humans , Male , Middle Aged , Neuropsychological Tests
18.
Pharmacol Biochem Behav ; 96(1): 67-74, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20417659

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.


Subject(s)
Attention/drug effects , Dronabinol/chemistry , Evoked Potentials, Visual/drug effects , Marijuana Smoking/adverse effects , Psychomotor Performance/drug effects , Visual Perception/drug effects , Adolescent , Adult , Attention/physiology , Cannabis/chemistry , Cross-Over Studies , Double-Blind Method , Dronabinol/administration & dosage , Evoked Potentials, Visual/physiology , Humans , Male , Marijuana Smoking/physiopathology , Photic Stimulation/methods , Psychomotor Performance/physiology , Reaction Time/drug effects , Reaction Time/physiology , Time Factors , Visual Perception/physiology , Young Adult
19.
J Psychopharmacol ; 24(5): 657-66, 2010 May.
Article in English | MEDLINE | ID: mdl-19329545

ABSTRACT

Human experimental models for anxiety may serve as translational tools for translating preclinical psychopharmacological investigations into human studies. For the evaluation of drugs of which pharmacokinetics and pharmacodynamics are unidentified, repeating measurements after drug administration is necessary for characterising the time course of drug effects. In experiment 1, a threat-of-shock paradigm and adaptations of the Trier mental arithmetic test and the Stroop colour naming test were repeated four times within a day to evaluate whether anxiety responses to this test battery remain stable after repeated testing. This procedure was repeated on 4 days in a second experiment to evaluate suitability of the paradigm for a crossover design with multiple sessions. Results indicate no reductions or changes in fear potentiated startle, the main outcome measure for the threat paradigm, over test sessions or days. Skin conductance responses and subjective ratings under threat-of-shock showed significant fluctuations but also no systematic decline over time. Finally, the threat paradigm and Stroop test resulted in small increases in reported state anxiety while mental arithmetic produced larger effects that diminished after the first test day. It is concluded that especially the startle paradigm could be a useful new instrument for screening new anxiolytic drugs.


Subject(s)
Anti-Anxiety Agents/pharmacology , Anxiety , Neuropharmacology/methods , Neuropsychological Tests , Adolescent , Adult , Anti-Anxiety Agents/adverse effects , Anti-Anxiety Agents/pharmacokinetics , Anxiety/drug therapy , Clinical Trials as Topic , Cross-Over Studies , Electromyography , Fear , Female , Galvanic Skin Response , Habituation, Psychophysiologic , Humans , Male , Mental Processes , Reflex, Startle , Reproducibility of Results , Stroop Test , Time Factors , Young Adult
20.
J Psychopharmacol ; 24(6): 839-45, 2010 Jun.
Article in English | MEDLINE | ID: mdl-19028837

ABSTRACT

Moderate doses of alcohol (blood alcohol concentration [BAC] of about 0.05%) may result in acute impairments at various levels of information processing. A number of reports have documented detrimental effects of moderate alcohol on the mismatch negativity (MMN), the electrocortical manifestation of a rapid (100 ms poststimulus) mechanism dedicated to the detection of unexpected auditory change (e.g., Jääskeläinen, et al., 1995). Recently, we and others identified a partial visual counterpart of the MMN, sometimes called the rareness-related negativity (RRN). Analogous to the MMN, the RRN evolves at about 100 ms after the unexpected change and was localized in visual cortex (Kenemans, et al., 2003). Rapid detection of unexpected events is important for everyday-life conditions like driving, prompting the question whether the visual RRN shows sensitivity to moderate alcohol similar to the MMN. In all, 16 subjects were tested either under moderate alcohol or under placebo. Unexpected visual change was implemented by presenting 2.4 versus 0.6 c/d gratings in pseudorandom sequences according to a deviant (10%)/standard (90%) schedule. The alcohol effects on MMN reported before were replicated. Furthermore, the RRN, defined as the difference between deviant and standard event-related potentials between 120 and 170 ms at Oz, was present under placebo but not under alcohol. It is concluded that moderate alcohol does indeed impair the rapid detection in visual cortex of unexpected changes. In contrast, electrocortical correlates of lower level sensory processing were still significantly present under alcohol.


Subject(s)
Attention/drug effects , Ethanol/pharmacology , Reaction Time/drug effects , Visual Cortex/drug effects , Visual Perception/drug effects , Acoustic Stimulation , Adolescent , Adult , Analysis of Variance , Auditory Perception/drug effects , Brain Mapping , Electroencephalography , Evoked Potentials, Auditory/drug effects , Evoked Potentials, Visual/drug effects , Female , Humans , Male , Photic Stimulation , Psychomotor Performance/drug effects , Signal Processing, Computer-Assisted
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