Empathy and prosocial behavior in response to sadness and distress in 6- to 7-year olds diagnosed with disruptive behavior disorder and attention-deficit hyperactivity disorder.

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.

TMS of the anterior intraparietal area selectively modulates orientation change detection during action preparation.

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.

Individual differences in the effects of salience and reward on impulse control and action selection.

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.

Genetic polymorphisms of the dopamine and serotonin systems modulate the neurophysiological response to feedback and risk taking in healthy humans.

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.

Catecholaminergic and cholinergic neuromodulation in autism spectrum disorder: A comparison to attention-deficit hyperactivity disorder.

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.

The image features of emotional faces that predict the initial eye movement to a face.

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.

fMRI-guided TMS on cortical eye fields: the frontal but not intraparietal eye fields regulate the coupling between visuospatial attention and eye movements.

It is well known that parts of a visual scene are prioritized for visual processing, depending on the current situation. How the CNS moves this focus of attention across the visual image is largely unknown, although there is substantial evidence that preparation of an action is a key factor. Our results support the view that direct corticocortical feedback connections from frontal oculomotor areas to the visual cortex are responsible for the coupling between eye movements and shifts of visuospatial attention. Functional magnetic resonance imaging (fMRI)-guided transcranial magnetic stimulation (TMS) was applied to the frontal eye fields (FEFs) and intraparietal sulcus (IPS). A single pulse was delivered 60, 30, or 0 ms before a discrimination target was presented at, or next to, the target of a saccade in preparation. Results showed that the known enhancement of discrimination performance specific to locations to which eye movements are being prepared was enhanced by early TMS on the FEF contralateral to eye movement direction, whereas TMS on the IPS resulted in a general performance increase. The current findings indicate that the FEF affects selective visual processing within the visual cortex itself through direct feedback projections.

Failure to condition to a cue is associated with sustained contextual fear.

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.

Event-related potentials and secondary task performance during simulated driving.

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.

fMRI evidence for both generalized and specialized components of attentional control.

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.

Abnormal spatial frequency processing in high-functioning children with pervasive developmental disorder (PDD).

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. SIGNIFICANCE: A basic abnormality in visual frequency processing is established in children with PDD.

Processing capacity in chronic pain patients: a visual event-related potentials study.

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.

Acute and subchronic effects of amitriptyline on processing capacity in neuropathic pain patients using visual event-related potentials: preliminary findings.

RATIONALE: Little is known about the effects of low doses of amitriptyline, prescribed in the treatment of neuropathic pain, on attentional processing capacity. OBJECTIVES: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The impact of chronic pain patients' psychotropic drug knowledge and warning labels on the decision whether to drive a car or not.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

The relationship between local and global processing and the processing of high and low spatial frequencies studied by event-related potentials and source modeling.

The processing of global and local elements and of low- and high-spatial frequencies are thought to be interrelated. Evidence for this stems from findings showing that brain localizations for global/local elements and for low/high spatial frequencies seem to overlap. The present study aimed to provide direct evidence that topographical differences between the processing of global and local visual elements can directly be explained by their spatial frequency content, and to study at which point in time this relation is present. This was done by studying the event-related potentials (ERPs) and source models elicited by unfiltered, low- or high-pass filtered hierarchical stimuli. Results showed that performance for global and local targets was affected by removing low and high spatial frequencies, respectively. ERP data indicated that at 250 ms, there was an interaction between the processing of global/local targets and of spatial frequencies because at this time-point removal of low spatial frequencies decreased activity associated with the processing of global targets. When localizing this effect, we found evidence implying that spatial frequency content indeed affected the brain region in which local/global targets were processed. Results implicated that the processing of global information depended on its low spatial frequency content, which was processed more laterally. Instead, processing of local information seemed to depend on its high spatial frequency content, which was processed more medially. Thereby, present results extend former results showing that global and local processing is dependent on spatial frequency and mapped retinotopically in the visual cortex.

Time-varying differences in evoked potentials elicited by high versus low spatial frequencies: a topographical and source analysis.

OBJECTIVE: To investigate time-varying differences in visual-evoked potentials (VEPs) and dipoles elicited by high versus low spatial frequencies. The main question was whether different spatial frequencies are processed in distinct cortical areas, especially after 100 ms. An additional question was whether and how a hemispheric balance in spatial frequency processing develops over time. METHODS: Stimuli were square-wave gratings, with spatial frequencies of 0.75, 1.5, and 6 c/d. VEPs and dipole models were analyzed at various latencies. RESULTS: For the time-window of 80-100 ms, spatial frequency-related differences in VEPs and dipoles in posterior regions as reported previously were replicated: lower spatial frequencies were associated with more positivity in the VEP and with more anterior and radial sources than high frequencies. However, after 100 ms differences in amplitude, but not in topography and dipoles, were found between the different spatial frequencies. Between 180-200 ms a right hemisphere dominance was found for all frequencies. CONCLUSIONS: After 100 ms, VEPs in response to different spatial frequencies seem to be generated in the same cortical areas. Also, no evidence for frequency-related hemispheric lateralization was found. SIGNIFICANCE: Insight is provided into the functional-anatomical basis of longer-latency frequency-related differences in processing.

Acute effects of nicotine on attention and response inhibition.

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.

Attention deficit and impulsivity: selecting, shifting, and stopping.

The present selective review addresses attention, inhibition, and their underlying brain mechanisms, especially in relation to attention deficit/hyperactivity disorders (AD/HD), and the effects of methylphenidate. In particular, event-related potential (ERP) studies suggest a deficit in the early-filtering aspect of selective attention in children with AD/HD. Results from stop tasks are consistent with impairments in stopping performance in AD/HD, but in children (as opposed to adults) these effects cannot be easily dissociated from more general impairments in attention to the task, and therefore an interpretation in terms of inhibitory control is not straightforward. On the other hand, the beneficial effects of methylphenidate are more specific to stopping, and there are no clearcut effects of methylphenidate on measures of selective attention. Even when group differences pertain specifically to stopping performance (as with adults with AD/HD), ERP evidence suggests at least a partial contribution of differences in switching attention to the stop signal, as revealed in measures of sensory cortex activation. ERP evidence from cued go/nogo tasks underlines the importance of taking into account the contribution of higher order control processes involved in anticipation of and preparation for task stimuli. It suggests that in certain conditions, expectancy, rather than response bias, contributes to increased behavioral response tendencies, and that a presumed index of response inhibition, the nogo N2, may rather reflect conflict monitoring. In sum, direct reflections of brain activity suggest that mechanisms of expectation and attention, rather than of response bias or inhibitory control, govern behavioral manifestations of impulsivity.

Electromyographic responses to emotional facial expressions in 6-7 year olds with autism spectrum disorders.

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.

Caffeine and visuo-spatial attention.

The effects of two doses of caffeine (1.5 and 3 mg/kg) on various aspects of visual selective attention were investigated in 24 healthy human subjects. Specific task conditions were compared to provide measures of selectivity for a location in the visual field, of distractibility, of selectivity among response alternatives, and of strategic influences. In two out of three tasks, caffeine speeded responses significantly. However, these effects did not differ across conditions within-task, so there was no indication that they were to due to (a) specific effect(s) on one or more of the attentional sub-functions. The results suggest that the beneficial effects of caffeine in low-load conditions cannot be attributed to reduced distractibility or increased suppression of task-irrelevant response tendencies.